The ride stability of an A-train 28-foot double tractor trailer when outfitted with different Roll Stability Control (RSC) systems with the same payload and suspension configurations is studied experimentally for various dynamic maneuvers. The primary goal of the study is to determine the effect of different commercially-available RSC systems on the extent of improvements they offer for increasing roll stability of commercial vehicles with double trailers, when subjected to limit-steering maneuvers that can rise during highway driving. A semitruck and two 28-foot trailers are modified for enduring the forces and moments that can result during testing. A load structure is used for placing the ballast loads within the trailers at a suitable height for duplicating the CG height of the trailers during their commercial use. Outriggers and jackknifing arresting mechanisms are used to prevent vehicle damage and ensure safety during the tests. The test vehicle is equipped with multiple sensors and cameras for the necessary measurements and observations. The analog and video data are time-synced for correlating the measurements with visual observation of the test vehicle dynamics in post-processing. An extensive number of tests are conducted at the Michelin Laurens Proving Grounds (MLPG) in Laurens, SC. The tests include evaluating each RSC system with different maneuvers and speeds until a rollover occurs or the vehicle is deemed to be unstable. The maneuvers that are used for the tests include: double lane change, sine-with-dwell, J-turn, and ramp steer maneuver. Both a steering robot and subjective driver are used for the tests. The test data are analyzed and the results are used to compare the three RSC systems with each other, and with trailers without RSC. The test results indicate that all three RSC systems are able to improve the speed at which rollover occurs, with a varying degree. For two of the systems, the rollover speed gained, when compared with trailers without RSC, is marginal. For one of the systems, there are more significant speed gains. Since most RSC systems are tuned for a conventional tractor-trailer, additional testing with some of the systems would be necessary to enable the manufacturers to better fine-tune the RSC control scheme to the dynamics of double trailers. / MS / The safety of driven semi-trailer trucks towing two trailers is analyzed in a study created to examine the behavior of the vehicle and its units during high speed, high maneuvering circumstances. The rolling over of a specific test truck is studied to study the ability of a common large vehicle to succeed in evasive or emergency maneuvers. Focus on the rolling over of a truck is placed in this project, as large freight vehicle rollovers are among the most popular and most dangerous type of accidents on highways today. A semi-trailer truck with two trailers, or double trailer vehicle, is instrumented with sensors and cameras to study several different characteristics associated with vehicle operation and conditions that incite rollover. The behavior of a double trailer vehicle is complicated due to the additional rotation joint between the adjacent trailers, where typical semi-trailer trucks (18-wheelers) only incorporate one: between the towing tractor and the towed trailer. Commercially available electronic appliances called Roll Stability Control (RSC) systems were designed to automatically control and apply the vehicle brakes under rollover conditions, and are installed and used individually to evaluate any improvements on the test vehicle’s ability to stay upright. Information regarding RSC system operation can be found. All vehicle testing is completed at a professional vehicle testing location in Laurens, SC and the same four test maneuvers are used to determine the effectiveness of each of the five RSC systems tested using data collected with the instrumented sensors. Different types of RSC systems exist due to different manners of operation, and are discussed in this document and analyzed. This project develops the conclusion that the five systems used during testing all improve vehicle stability, but provide differing results in doing so, largely due to their different operations. Therefore, commercially available RSC systems are proven to work differently and provide different results. Recommendations for further testing of RSC systems is provided. Although no recommendations are made regarding the tested RSC systems, the collected data show large, double trailer freight vehicles are more stable when using any of the tested commercially available RSC systems, especially during evasive maneuvering or emergency situations. These findings can bring immediate improvements to large freight vehicle operation and safety.

This thesis is a study into the response and seismic safety of three-dimensional multi-storey concrete structures under concurrent orthogonal seismic excitations. It employs the nonlinear time-history method as its analysis tools. Time-history analyses rely heavily on their utilised earthquake records. Accordingly, this study examines the different approaches of selecting earthquake suites and develops a methodology of selecting representative earthquake scenarios. This methodology is credibly implemented in selecting a far- and a near field suites representative of the New Zealand seismic hazard. The study investigates the response of 6-, 9- and 12-storey concrete structures of different n-X-bays × m-Y-bays. Bidirectional responses of these considered structures are examined and consequently the current combination rules are scrutinised. Consequently this study strongly recommends the use of the 40-percent combination rule in lieu of the widely used 30-percent rule; and the use of time-history analysis in lieu of quasi/equivalent static and response modal analysis methods to avoid their strong dependence on combination rules. An intensive study is conducted employing the incremental dynamic analysis (IDA) technique to investigate structural demands of interstorey drifts, lateral storey drifts and storey accelerations. The study utilises the developed far-field suite and identifies the 50th and 90th percentile demands. Hence it provides easy-to-use expressions to facilitate rapid calculation of the structural demands and the effects of biaxial interactions. An implementation into the Demand and Capacity Factor Design (DCFD) format is presented that infers confidence in the performance levels of the considered structures. The study also draws attention to the importance of considering storey accelerations as their storey values reach as high as 10 × PGA. A sensitivity study is conducted by repeating the IDA investigation while using the developed near-field suite. Subsequently a comparison between the near- and the far-field results is conducted. The results were markedly similar albeit of less magnitudes until the (seismic hazard) intensity measure IM = Sa(T₁) = 0.4g when the near-field results show sudden flat large increase in demands suggesting a brittle collapse. This is attributed to the higher content of the higher mode frequencies contained in near-field ground motions. Finally, the study examines the (vectorial) radial horizontal shear demands in columns and beam-column joints of the previous far- and near-field studies. The combined radial shear demands in corner, edge and internal columns and joints are evaluated that roughly show a square-root proportional relationship with IM that exhibit somewhat brittle failure at IM ≥ 0.35g. Shears demands in the (4-way) internal columns and the (2-way) corner joints show highest magnitude in their respective class. The results suggest transverse joint shear reinforcement of 1.5, 1.0 and 0.5 of the longitudinal reinforcement of the neighbouring beam respectively for corner, edge and internal joints. An implementation of a proposed practical (and simpler) DCFD format shows satisfactory confidence in columns performance in shear up to IM = 0.35g, conversely to joints unsatisfactory performance in shear at the onset of inelastic behaviour (IM > 0.05g).

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized for combination particles were water / EA, water / IPA, and water / IPA:EA 1:10 (w/w). IPA was found to be the optimum anti-solvent for producing combination particles of AS and IB with the smallest size. These combination particles showed uniform co-deposition during in vitro aerosol performance testing from the Novolizer®. Pilot molecular modeling studies in conjunction with the analysis of particle interactions using HINT provided an improved understanding of the possible interactions between AS and IB within a combination particle matrix.

The potential antitumor activity of mixed CB1/CB2 cannabinoid receptor agonists, such as the aminoalkylindole WIN55,212-2 (WIN2), has been extensively studied, but little information is available as to their potential interaction with conventional cancer therapies, such as ionizing radiation (IR). In the present work, we investigated the effects of WIN2 on the antiproliferative effects of radiation in human (MCF-7 and MDA-MB-231) and murine (4T1) breast cancer cells, as well as an immortalized human breast epithelial cell line (MCF-10A). WIN2 or radiation alone inhibited breast tumor growth, while the combination of WIN2 and radiation was more effective than either agent alone in breast cancer cells. WIN2 showed lower potency in MCF-10A cells than MCF-7 cells, but was still able to augment the effects of radiation at higher doses. The stereoisomer of WIN2, WIN55,212-3 (WIN3) failed to inhibit growth or potentiate the growth-inhibitory effects of radiation, indicating stereospecificity in all cell lines tested. The combination of WIN2 and IR was examined in vivo but the results were inconclusive. Interestingly, while other aminoalkylindoles, pravadoline and JWH-015, enhanced the antiproliferative effects of radiation, this was not the case for other synthetic cannabinoids (i.e., nabilone, CP55,940 and methanandamide) or phytocannabinoids (i.e., ∆9-tetrahydrocannabinol and cannabidiol). The antiproliferative actions of WIN2 were not ameliorated by CB1, CB2, TRPV1, or PPAR receptor antagonists, suggesting the possibility of a novel site of action. Studies utilizing sphingosine-1-phosphate (S1P) agonists and estradiol suggest that WIN2 interferes with S1P signaling in cell proliferation, but agonist stimulated [³⁵S]GTPγS binding assays show that this antagonism is not occurring at the level of S1P receptors. In addition, WIN2 did not alter radiation-induced DNA damage or the rate of DNA repair based on γH2AX staining. Treatment with WIN2 and radiation promoted both autophagy and senescence, but not apoptosis or necrosis. Time course studies combined with senescence and cell death data suggest that radiation-induced senescence, while WIN2 induced classical growth arrest and the WIN2/IR combination produced parallel mechanisms of both senescent growth arrest and classical growth arrest. Taken together, these findings raise the possibility that aminoalkylindole compounds targeting a novel site of action represents a potential strategy to augment the effectiveness of radiation treatment in breast cancer.

The dissertation (diploma thesis) with the topic "Comics as the medium of the artistic expression" consists of theoretical and practical parts. The theoretical part represents a definition of the comics, its short history and some important terms of the comics terminology. Next this part concerns with specific narrative constructions of the comics medium and also describes functions and cooperation of the visual and verbal components. In the individual charter is shortly described Japanese comics (manga), its characteristic and different aspects against the classic European and American comics. The end of the theoretical part is dedicated to the theory of the artistic expression and its particular elements, which are used in the comics. The practical part comprising the analysis of two classic comics works and one Japanese manga. Namely it is The Crow, The Crow: Skinnig the Wolves and The City of Light. These works were chosen intentionally because of their technical, thematic and cultural aspects, so the analysis can work with the wider scale of the artistic elements. The dissertation tries to defend the opinion, that the comics medium is multifunctional, it can contain full-blown artistic expression and it is able to work with any content. For better specification there are contained some...

Title: Presence and effectiveness of the pick-and-roll in chosen ŽBL and Eurocup Women teams (comparative study) Objective of thesis: This Master's thesis is further development of the Bachelor's thesis that was defended in May 2014. The objective of the thesis is to find out the presence and effectiveness of pick-and-roll. This research was done on selected Eurocup Women teams and consequently compared with results of the ŽBL teams according to the Bachelor's thesis. Methods: Regarding the quantitative research, the thesis was based on the collective method of secondary information in that case secondary statistical analysis and direct observation of recorded data. Results: The presence of pick-and-roll in ŽBL teams was comparable to the Eurocup Women teams. The teams playing European competition had similar effectiveness of pick-and-roll as the teams playing ŽBL (Czech competition). Key words: Basketball, ŽBL (women basketball league), Eurocup Women, combination based on screen, basketball plays

In der vorliegenden Arbeit wurden neue Untersuchungsmöglichkeiten mit dem BacT/Alert 3D Mykobakterien-Testsystem erprobt. Erstens wurden Untersuchungen durchgeführt, um die Testkonzentrationen für Protionamid (PTH) und Linezolid (LIZ) für die standardmäßige Empfindlichkeitstestung von M. tuberculosis (Mtb) mit dem BacT/Alert 3D-System festzulegen. Dazu wurden die MHK-Werte für 32 Mtb-Stämme bestimmt: Referenzstamm Mtb H37Rv, sensible Patientenstämme, Patientenstämme mit verschiedenen Resistenzen (u. a. PTH-Resistenz) sowie eigens für die Arbeit isolierte LIZ-resistente Mutanten. Die PTH-MHK betrug für 20 von 21 sensiblen Mtb-Stämmen einschließlich des Referenzstammes Mtb H37Rv 0,125 - 1 mg/l (0,25 mg/l bei 11 von 21 Stämmen). Lediglich ein Stamm mit Resistenz gegenüber Isoniazid, Ethambutol und Streptomycin fiel mit einer etwas erhöhten PTH-MHK von 2 mg/l auf. Sechs PTH-resistente Stämme (z. T. mit anderen Resistenzen gegenüber Erstrang-Antituberkulotika) zeigten PTH-MHK von 4 - 16 mg/l. Die Gruppen der PTH-sensiblen und resistenten Stämme zeigten ein bimodales Verteilungsmuster, das mit einem Schwellenwert von 2 mg PTH/l gut zu differenzieren ist. Für die standardmäßige Durchführung der Empfindlichkeitstestung gegenüber PTH mit dem BacT/Alert 3D-System empfehlen wir deshalb eine PTH-Testkonzentration von 2 mg/l. Die LIZ-MHK betrug für 20 sensible Mtb-Stämme (inklusive Referenzstamm Mtb H37Rv) und sieben Stämme mit verschiedenen Resistenzen gegenüber Erstrang-Antituberkulotika 0,25 - 2 mg/l (0,5 mg/l bei 17 von 27 Stämmen). Für die vier isolierten LIZ-resistenten Mutanten betrug die LIZ-MHK 8 - 16 mg/l. Es zeigt sich auch bei der Verteilung der LIZ-MHK ein bimodales Verteilungsmuster; die Gruppen der sensiblen und resistenten Stämme sind gut zu differenzieren. Wir empfehlen für die standardmäßige Durchführung der Empfindlichkeitstestung gegenüber LIZ mit dem BacT/Alert 3D-System eine LIZ-Testkonzentration von 4 mg/l. Die festgestellten MHK-Werte von PTH und LIZ und die vorgeschlagenen Testkonzentrationen entsprechen Ergebnissen aus der Literatur, die mit ähnlichen Methoden erhoben wurden. Zweitens wurden mit dem BacT/Alert 3D-System Untersuchungen zur Kombinationstestung von Antituberkulotika bei Mtb und Stämmen des MAC-Komplexes durchgeführt, bisher liegen keine Publikationen für Untersuchungen von Wirkstoff-Kombinationen bei Mykobakterien mit diesem System vor. Es wurde geprüft, ob die MHK eines Antituberkulotikums durch die Zugabe einer subinhibitorischen Menge eines anderen Antituberkulotikums verändert wird. Bei Mtb wurden dazu folgende Kombinationen geprüft: Rifampicin (RMP) + LIZ, Moxifloxacin + LIZ, Isoniazid + PTH, RMP + PTH, PTH + LIZ. In keinem Fall konnten signifikante Effekte beobachtet werden. Ein tendenziell synergistischer Effekt der PTH-RMP-Kombination beim Stamm Mtb H37Rv (Reduktion der RMP-MHK um eine Stufe) wurde durch die Analyse der Wachstumskinetik des Stammes unterstützt. Bei zufällig ausgewählten Stämmen des MAC-Komplexes wurde die Kombination Ciprofloxacin (CIP) + Ethambutol (EMB) geprüft. Es zeigte sich bei sieben von zehn Stämmen eine Reduzierung der CIP-MHK um mindestens drei Stufen bei Zugabe einer subinhibitorischen Konzentration von EMB. Dieser synergistische Effekt wurde bereits in den 1990er Jahren mit einer ähnlichen Methode festgestellt, allerdings ohne die Stämme des MAC-Komplexes zu differenzieren (Arbeitsgruppe von S. Hoffner). Interessanterweise handelte es sich bei den von uns untersuchten Stämmen, bei denen dieser synergistische Effekt nachgewiesen wurde, um M. avium-Stämme. Diese Problematik sollte weiter verfolgt werden, da sich daraus Konsequenzen für die Therapieempfehlung ergeben könnten.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martina Sýkorová Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on impact of selected tyrosine kinase inhibitors on multidrug resistance mediated by ABC drug efflux transporters Tyrosine kinases are an important class of enzymes controlling cell proliferation, carcinogenesis, apoptosis and cell differentiation. Deregulation of these enzymes can transform normal cell into a cancerous one. Blocking their function by tyrosine kinase inhibitors (TKi) is considered a promising treatment for various types of cancer. ATP-binding cassette (ABC) transporters form a family of transmembrane proteins that can transport a wide variety of substrates across biological membranes via ATP-dependent drug efflux pumps. They modulate drug pharmacokinetics, but on the other hand, lead to therapy failure due to overexpression in cancer cells. In our previous study, we evaluated inhibition properties of two selected TKi (alectinib, brivanib) in MDCKII cell lines (parent one and those transduced with human ABCB1, ABCC1 and ABCG2). Alectinib significantly inhibited ABCB1, ABCG2 but not ABCC1 transporter. Brivanib showed triple inhibition of all studied transporters. In the present work, we...

Au long des dernières décennies, des importants avancements ont été réalisés dans le domaine de la reconnaissance de la parole à grand vocabulaire. Un des défis à relever dans le domaine concerne la réduction des coûts de développement nécessaires pour construire un nouveau système ou adapter un système existant à une nouvelle tâche, langue ou dialecte. Les systèmes de reconnaissance de la parole à l’état de l’art sont basés sur les principes de l’apprentissage statistique, utilisant l’information fournie par deux modèles stochastiques, un modèle acoustique (MA) et un modèle de langue (ML). Les méthodes standards utilisées pour construire ces modèles s’appuient sur deux hypothèses de base : les jeux de données d’apprentissage sont suffisamment grands, et les données d’apprentissage correspondent bien à la tâche cible. Il est bien connu qu’une partie importante des coûts de développement est dû à la préparation des corpora qui remplissent ces deux conditions, l’origine principale des coûts étant la transcription manuelle des données audio. De plus, pour certaines applications, notamment la reconnaissance des langues et dialectes dits "peu dotés", la collecte des données est en soi une mission difficile. Cette thèse a pour but d’examiner et de proposer des méthodes visant à réduire le besoin de transcriptions manuelles des données audio pour une tâche donnée. Deux axes de recherche ont été suivis. Dans un premier temps, des méthodes d’apprentissage dits "non-supervisées" sont explorées. Leur point commun est l’utilisation des transcriptions audio obtenues automatiquement à l’aide d’un système de reconnaissance existant. Des méthodes non-supervisées sont explorées pour la construction de trois des principales composantes des systèmes de reconnaissance. D’abord, une nouvelle méthode d’apprentissage non-supervisée des MAs est proposée : l’utilisation de plusieurs hypothèses de décodage (au lieu de la meilleure uniquement) conduit à des gains de performance substantiels par rapport à l’approche standard. L’approche non-supervisée est également étendue à l’estimation des paramètres du réseau de neurones (RN) utilisé pour l’extraction d’attributs acoustiques. Cette approche permet la construction des modèles acoustiques d’une façon totalement non-supervisée et conduit à des résultats compétitifs en comparaison avec des RNs estimés de façon supervisée. Finalement, des méthodes non-supervisées sont explorées pour l’estimation des MLs à repli (back-off ) standards et MLs neuronaux. Il est montré que l’apprentissage non-supervisée des MLs conduit à des gains de performance additifs (bien que petits) à ceux obtenus par l’apprentissage non-supervisée des MAs. Dans un deuxième temps, cette thèse propose l’utilisation de l’interpolation de modèles comme une alternative rapide et flexible pour la construction des MAs pour une tâche cible. Les modèles obtenus à partir d’interpolation se montrent plus performants que les modèles de base, notamment ceux estimés à échantillons regroupés ou ceux adaptés à la tâche cible. Il est montré que l’interpolation de modèles est particulièrement utile pour la reconnaissance des dialectes peu dotés. Quand la quantité de données d’apprentissage acoustiques du dialecte ciblé est petite (2 à 3 heures) ou même nulle, l’interpolation des modèles conduit à des gains de performances considérables par rapport aux méthodes standards. / One of the outstanding challenges in large vocabulary automatic speech recognition (ASR) is the reduction of development costs required to build a new recognition system or adapt an existing one to a new task, language or dialect. The state-of-the-art ASR systems are based on the principles of the statistical learning paradigm, using information provided by two stochastic models, an acoustic (AM) and a language (LM) model. The standard methods used to estimate the parameters of such models are founded on two main assumptions : the training data sets are large enough, and the training data match well the target task. It is well-known that a great part of system development costs is due to the construction of corpora that fulfill these requirements. In particular, manually transcribing the audio data is the most expensive and time-consuming endeavor. For some applications, such as the recognition of low resourced languages or dialects, finding and collecting data is also a hard (and expensive) task. As a means to lower the cost required for ASR system development, this thesis proposes and studies methods that aim to alleviate the need for manually transcribing audio data for a given target task. Two axes of research are explored. First, unsupervised training methods are explored in order to build three of the main components of ASR systems : the acoustic model, the multi-layer perceptron (MLP) used to extract acoustic features and the language model. The unsupervised training methods aim to estimate the model parameters using a large amount of automatically (and inaccurately) transcribed audio data, obtained thanks to an existing recognition system. A novel method for unsupervised AM training that copes well with the automatic audio transcripts is proposed : the use of multiple recognition hypotheses (rather than the best one) leads to consistent gains in performance over the standard approach. Unsupervised MLP training is proposed as an alternative to build efficient acoustic models in a fully unsupervised way. Compared to cross-lingual MLPs trained in a supervised manner, the unsupervised MLP leads to competitive performance levels even if trained on only about half of the data amount. Unsupervised LM training approaches are proposed to estimate standard back-off n-gram and neural network language models. It is shown that unsupervised LM training leads to additive gains in performance on top of unsupervised AM training. Second, this thesis proposes the use of model interpolation as a rapid and flexible way to build task specific acoustic models. In reported experiments, models obtained via interpolation outperform the baseline pooled models and equivalent maximum a posteriori (MAP) adapted models. Interpolation proves to be especially useful for low resourced dialect ASR. When only a few (2 to 3 hours) or no acoustic data truly matching the target dialect are available for AM training, model interpolation leads to substantial performance gains compared to the standard training methods.

Nas duas últimas décadas, houve um enorme aumento no número de estruturas proteicas resolvidas, e entre elas há uma variedade imensa de proteínas com mais de uma conformação observada. Essa quantidade incontestável de dados experimentais corroboram a hipótese de que cada proteína exista num espaço conformacional próprio, onde ela possa adotar inúmeras conformações, umas mais distintas ou estáveis que outras. Essas conformações estão distribuídas nesse espaço de acordo com sua energia potencial, que pode ser definida como uma superfície cheia de rugosidades, poços e barreiras energéticas. Duas conformações distantes nesse espaço são muito diferentes entre si, enquanto que duas conformações próximas são mais semelhantes. Da mesma forma, se distinguem os movimentos necessários para passar de uma conformação à outra. Para uma proteína passar de um estado a outro, geralmente identificados com grandes mudanças conformacionais, é necessário um movimento coletivo. Por ser de grande amplitude, esse tipo de movimento ocorre com baixa frequência, e dificilmente é observado em simulações clássicas de dinâmica molecular. Assim, existem métodos dedicados à obtenção destes movimentos, como a análise de modos normais, os modelos de redes elásticas e a análise de componentes principais. Neste trabalho, adaptamos o método de transformada de Fourier para recuperar modos harmônicos que compõem uma trajetória simulada suficientemente longa para analisar três proteínas distintas quanto a seus movimentos biológicos de importância funcional. Uma é a DEA, cuja simetria hexagonal observamos influenciar nos modos coletivos e na transição entre estados. Outra é a MosR, que simulamos em seus dois estados diferentes, oxidado ou reduzido, para encontrar como a oxidação é capaz de impedir os movimentos coletivos que levam à conformação ligada ao DNA. Nestas duas proteínas, observamos que nenhum modo por si só é responsável pela transição entre as conformações experimentais, mas que eles dependem de outros modos ou outras mudanças conformacionais ocorrendo de forma combinada. A terceira proteína analisada é um regulador transcricional, assim como a MosR, a ElrR, cuja estrutura é conhecida somente na forma apo. Neste trabalho, construímos modelos da ElrR ligada ao DNA pela combinação linear de modos harmônicos para modelar um possível ligante na nova conformação do sítio alostérico. As amplitudes usadas nessa combinação foram obtidas pelo método de mínimos quadrados, visando minimizar o desvio em relação somente às coordenadas que as hélices de reconhecimento devem apresentar para se ligar ao sítio de DNA. Este prognóstico foi feito pela análise metódica das estruturas de 27 reguladores transcricionais, homodiméricos com o motivo HTH, em complexo com DNA. Essa análise também nos permitiu descrever a estereoquímica do encaixe das hélices de reconhecimento nos sulcos maiores do DNA com novos parâmetros geométricos, intimamente relacionados com a simetria do complexo, com a sequência de resíduos das hélices de reconhecimento e com a sequência de bases do sítio de DNA, de forma a auxiliar na modelagem de novos complexos. / There was an enormous increase in the deposited protein structures in the past two decades, among them there is a great variety of proteins with more than one observed conformation. This undenieble amount of experimental data ratify the hypothesis that each protein posseses its own conformational space, where it can adopt countless conformations, some more distinct or stable than others. These conformations are distributed in the space according to its potential energy, which maybe defined as a rough landscape fulled with energetic wells and barriers. Two conformations lying apart from each other in this landscape do not carry much resemblances, while neighbouring conformations are very similar. The motions required to get one conformation to another are just as distinguishable. There must be a collective motion inbetween two states of a protein, commonly characterized by large conformation changes. This type of motion is related to large amplitudes and low frequencies, thus it is hardly seen in classical molecular dynamics simulations. Therefore, there are dedicated methods to obtain these motions, as normal modes analysis, elastic network models and essential dynamics. In this work we adapted the method of Fourier transform filtering to retrieve harmonic modes that compose a simulated trajectory and thus analise the biological motions with functional importance of three distinct proteins. One is DEA, which hexagonal symmetry was observed to affect its collective motions and the transition between biological states. Another protein is MosR, which we simulated in two different states, oxidized or reduced, to learn how the formation of a disulphide bridge is able to preclude the collective motions that lead to a DNA-binding conformation. With these two proteins we observed that no mode by itself is responsible for the transition between experimental conformations, and they actually depend on other conformational changes occurring in a combined manner. The third protein that we analised, ElrR, is a transcriptional regulator, like MosR, which structure is known only on its apo form. Hence in this work we built models of ElrR bound to DNA by the linear combination of harmonic modes aiming to model a ligand that would fit in the allosteric site upon the conformational changes driven by the collective motions. The amplitudes we used in this method were calculated by the least square method to minimize the deviation to the positions of the recognition helices when bound to the DNA. This prognostic of the target position of the recognition helices was made upon the methodical analysis of 27 structures of homodimeric transcriptional regulators, that present the Helix-Turn-Helix motif, complexed with DNA. This approach allowed us to describe the stereochemical fitting of the recognition helices into the DNA major grooves with new geometrical parameters intimatelly related to the symmetry of the complex, the residue sequence of the recognition helices and the base sequence of the DNA site, providing thus support to model new complexes.