Thesis (PhD (Mathematics))--University of Stellenbosch, 2010. / Contains bibliography. / ENGLISH ABSTRACT: See full text for summary. / AFRIKAANSE OPSOMMING: Sien volteks vir opsomming

La demande pour les ressources énergétiques est en hausse alors que leur disponibilité est en baisse. Dans ce contexte, l’industrie du transport et de l’énergie est à la recherche de petits moteurs efficaces et puissants et le Rim Rotor Rotary Ramjet Engine (R4E) pourrait correspondre à ces critères. Or, en ce moment, le potentiel de ce moteur est limité, car son compresseur supersonique entraîne des pertes d’efficacité lorsque le rotor tourne à son nombre de Mach tangentiel optimal qui est de 2. Le présent mémoire compile toutes les notions requises pour comprendre le fonctionnement d’un compresseur supersonique lors de son démarrage et de concevoir le compresseur le plus approprié pour le R4E, tant en démarrage qu’en régime permanent. Pour se faire, des concepts de cascades inspirés des compresseurs et des méthodes de démarrage des moteurs ramjet actuels ont été générés et validés à l’aide de modèles analytiques. Les concepts sont par la suite essayés expérimentalement sous la forme de cascades à l’aide d’une soufflerie supersonique. Bien que le modèle analytique montre que les cascades munies de canaux de purge soient plus performantes et plus robustes en conditions off-design, ces dernières n’ont jamais démarré lors des expérimentations même si les canaux ont été agrandis et multipliés. Ainsi, parmi tous les concepts essayés, celui qui démarre par survitesse et qui comporte des canaux de succion de couche limite à son col a donné les meilleurs résultats. Il est très stable et permet d’obtenir un ratio de pression statique de 4.25 et un recouvrement de pression totale de 89 %, pour une efficacité isentropique de 92 % à un nombre de Mach tangentiel de 2. Par contre, il est à noter qu’il n’a pas été possible de mesurer la pression totale. Elle a plutôt été estimée à partir des images de strioscopie tirées lors des essais. Comme on ne dispose pas d’une structure permettant d’essayer le compresseur rotatif à Mach 2, il a fallu approximer l’influence de l’accélération centrifuge sur l’écoulement de la cascade et trouver un moyen d’intégrer le nouvel aubage à la roue. Un modèle permettant d’estimer les paramètres d’une couche limite se développant sur une plaque plane en rotation a permis de déduire que l’accélération transverse n’aurait qu’un effet légèrement favorable, puisqu’il permet d’amincir l’épaisseur de déplacement, réduisant ainsi les risques d’interaction en la couche limite et les chocs. Finalement, les canaux de succion de couche limite du compresseur pourraient permettre d’alimenter un système de refroidissement qui limiterait la température à la jante à 820 K. Le R4E pourrait devenir l’avenir des systèmes de régénération électrique pour les véhicules hybrides. Il serait aussi intéressant pour une utilisation dans les petites centrales thermiques des régions éloignées. Ce grand potentiel d’utilisation provient de la grande densité de puissance du moteur, de sa simplicité et de son très faible coût de fabrication et de maintenance.

Thesis (DSc (Mathematical Sciences))--University of Stellenbosch, 2007. / ENGLISH ABSTRACT: (Math symbols have changed) Wavelet and subdivision techniques have developed, over the last two decades, into powerful mathematical tools, for example in signal analysis and geometric modelling. Both wavelet and subdivision analysis are based on the concept of a matrix–refinable function, i.e. a finitely supported matrix function which is self-replicating in the sense that it can be expressed as a linear combination of the integer shifts of its own dilation with factor 2: F = TAF = å k∈Z F(2 ・ −k)Ak. The coefficients Ak, k ∈ Z of d × d matrices, of this linear combination constitute the so-called matrix- mask sequence. Wavelets are in fact constructed as a specific linear combination of the integer shifts of the 2-dilation of a matrix- refinable function cf. [2; 9], whereas the convergence of the associated matrix- subdivision scheme c0 = c, cr+1 = SAcr, r ∈ Z+, SA : c = (ck : k ∈ Z) 7→ SAc = å ℓ∈Z Ak−2ℓ cℓ : k ∈ Z ! , subject to the necessary condition that rank := dim   \ ǫ∈{0,1} n y ∈ Rd : Qǫy = y o   > 0, Qǫ := å j∈Z Aǫ+2j, ǫ ∈ {0, 1}, ( cf. [26]) , implies the existence of a finitely supported matrix- function which is refinable with respect to the mask coefficients defining the refinement equation and the subdivision scheme. Throughout this thesis, we investigate in time–domain for a given matrix mask sequence, the related issues of the existence of a matrix–refinable function and the convergence of the corresponding matrix– cascade algorithm, and finally we apply some results to the particular research area of Hermite interpolatory subdivision schemes. The dissertation is organized as follows: In order to provide a certain flexibility or freedom over the project, we established in Chapter 1 the equivalence relation between the matrix cascade algorithm and the matrix subdivision scheme, subject to a well defined class of initial iterates. Despite the general noncommutativity of matrices, we make use in the full rank case Qǫ = I, ǫ ∈ {0, 1}, of a symbol factorization, to develop in Chapter 2 some useful tools, yielding a convergence result which comes as close to the scalar case as possible: we obtained a concrete sufficient condition on the mask sequence based on the matrix version of the generating function introduced in [3, page 22] for existence and convergence. Whilst the conjecture on nonnegative masks was confirmed in 2005 by Zhou [29], our result on scalar case provided a progress for general mask sequences. We then applied to obtain a new one-parameter family of refinable functions which includes the cardinal splines as a special case, as well as corresponding convergent subdivision schemes. With the view to broaden the class of convergent matrix-masks, we replaced in chapter 3 the full rank condition by the rank one condition Qǫu = u, ǫ ∈ {0, 1}, u := (1, . . . , 1)T, then improved the paper by Dubuc and Merrien [13] by using the theory of rank subdivision schemes by Micchelli and Sauer [25; 26], and end up this improvement with a generalization of [13, Theorem 13, p.8] in to the context of rank subdivision schemes. In Chapter 4, we translated the concrete convergence criteria of the general theory from Theorem 3.2, based on the r-norming factor introduced in [13, Definition 6, p.6], into the context of rank, factorization and spectral radius (cf. [26]), and presented a careful analysis of the relationship between the two concepts. We then proceed with generalizations and improvements: we classified the matrix cascade algorithms in term of rank = 1, 2, . . . , d, and provided a complete characterization of each class with the use of a more general r−norming factor namely τ(r)-norming factor. On the other hand, we presented numerical methods to determine, if possible, the convergence of each class of matrix cascade algorithms. In both the scalar and matrix cases above, we also obtained explicitly the geometric constant appearing in the estimate for the geometric convergence of thematrix-cascade algorithm iterates to the matrix- refinable function. This same geometric convergence rate therefore also holds true for the corresponding matrix–cascade algorithm. Finally, in Chapter 5, we apply the theory and algorithms developed in Chapter 4 to the particular research area of Hermite interpolatory subdivision schemes: we provided a new convergence criterium, and end up with new convergence ranges of the parameters’ values of the famous Hermite interpolatory subdivision scheme with two parameters, due to Merrien [23]. / AFRIKAANSE OPSOMMING :(Wiskundige simbole het verander) Golfie en subdivisietegnieke het oor die afgelope twee dekades ontwikkel in kragtige wiskundige gereedskap, byvoorbeeld in seinanalise en geometriesemodellering. Beide golfie en subdivisie analise is gebaseer op die konsep van ’n matriks-verfynbare funksie; oftewel ’n eindig-ondersteunde matriksfunksie F wat selfreproduserend is in die sin dat dit uitgedruk kan word as ’n lineêre kombinasie van die heelgetalskuiwe van F se eie dilasie met faktor 2: F = Σ F(2 · −α)A(α), met A(α), α ∈ Z, wat aandui die sogenaamde matriks-masker ry. Golfies kan dan gekonstrueer word as ’n spesifieke lineêre kombinasie van die funksie ry {F(2 · −α) : α ∈ Z} (sien [2; 9]), terwyl die konvergensie van die ooreenstemmende matriks-subdivisie skema cº = c, cr+1 =(Σ β∈Z A(α − 2β) cr(β) : α ∈ Z ! , r ∈ Z+, onderhewig aan die nodige voorwaarde dat rank := dim   \ ǫ∈{0,1} n y ∈ Rd : Qǫy = y o   > 0, Qǫ := å α∈Z A(ǫ + 2α), ǫ ∈ {0, 1}, (sien [27]) die bestaan impliseer van ’n eindig-ondersteunde matriksfunksie F wat verfynbaar ismet betrekking tot diemaskerko¨effisi¨entewat die subdivisieskema definieer, en in terme waarvan die limietfunksie F van die subdivisieskema uitgedruk kan word as F = å α∈Z F(· − α)c(α). Ons hoofdoel hier is om , in die tydgebied, en vir ’n gegewematriks-masker ry, die verwante kwessies van die bestaan van ’nmatriks-verfynbare funksie en die konvergensie van die ooreenstemmende matriks-kaskade algoritme, en matriks-subdivisieskema, te ondersoek, en om uiteindelik sommige van ons resultate toe te pas op die spesifieke kwessie van die konvergensie van Hermite interpolerende subdivisieskemas. Summary v Eerstens, in Hoofstuk 1, ondersoek ons die verwantskap tussen matriks-kaskade algoritmes en matriks-subdivisie skemas, met verwysing na ’n goedgedefinieerde klas van begin-iterate. Vervolgens beskou ons die volle rang geval Qǫ = I, ǫ ∈ {0, 1}, om, in Hoofstuk 2, nuttige gereedskap te ontwikkel, en wat daarby ’n konvergensie resultaat met ’n sterk konneksie ten opsigte van die skalaar-geval oplewer. Met die doelstelling om ons klas van konvergente matriks-maskers te verbreed, vervang ons, in Hoofstuk 3, die volle rang voorwaarde met die rang een voorwaarde Qǫu = u, ǫ ∈ {0, 1}, u := (1, . . . , 1)T, en verkry ons dan ’n verbetering op ’n konvergensieresultaat in die artikel [14] deur Dubuc en Merrien, deur gebruik te maak van die teorie van rang subdivisieskemas van Micchelli en Sauer [26; 27], waarna ons die resultaat [14, Stelling 13, page 8] na die konteks van rang subdivisieskemas veralgemeen. InHoofstuk 4 herlei ons die konkrete konvergensie kriteria van Stelling 3.2, soos gebaseer op die r-normerende faktor gedefinieer in [14, Definisie 6, page 6] , na die konteks van rang, faktorisering en spektraalradius (sien [27]), en gee ons ’n streng analise van die verwantskap tussen die twee konsepte. Verder stel ons dan bekend ’n nuwe klassifikasie van matriks-kaskade algoritmes ten opsigte van rang, en verskaf ons ’n volledige karakterisering van elke klasmet behulp van ’nmeer algemene r-normerende faktor, nl. die τ(r)-normerende faktor. Daarby gee ons doeltreffende numeriesemetodes vir die implementering van ons teoretiese resultate. Ons verkry ook eksplisiet die geometriese konstante wat voorkom in die afskatting van die geometriese konvergensie van die matriks-kaskade algoritme iterate na die matriks-verfynbare funksie. Ten slotte, in Hoofstuk 5, pas ons die teorie en algoritmes ontwikkel in Hoofstuk 4 toe om die konvergensie van Hermite-interpolerende subdivisieskemas te analiseer. Spesifiek lei ons ’n nuwe konvergensie kriterium af, wat ons dan toepas om nuwe konvergensie gebiede vir die parameter waardes te verkry vir die beroemde Hermite interpolerende subdivisieskema met twee parameters, soos toegeskryf aan Merrien [24].

Unmanned ground mobile robots are land-based robots which do not have a human passenger on board. They can be either autonomous, or controlled via telecommunication. For navigational purposes, GPS is often used. However, the GPS signal can be distorted in obstructive environments such as tunnels, urban canyons, and dense forests. IMUs can be used to provide an internal navigational solution, free from external input. However, low cost IMUs are prone to various intrinsic sources of error, which leads to large errors in the long run. Using the short term accuracy of the IMU, and the long term accuracy of the GPS, these two technologies are often integrated to combine the aforementioned aspects of the two systems. For integration of the two, various methods are implemented. Such integration methods include Particle Filters, and Kalman Filters. Kalman Filters are commonly used due to their simplicity in calculations. However, the Kalman Filter linearizes the nonlinear error estimates which are inherent with low cost IMUs. The Kalman Filter also does not account for IMU measurement drift, which is present when the measurement unit is used for a long period of time. In this thesis, a Parallel Cascade Identification (PCI) algorithm is augmented with the Kalman Filter (KF) to model the nonlinear errors which are intrinsic to the low cost IMU. The method of integration used was 2D GPS/RISS loosely coupled integration using a Kalman Filter. The PCI algorithm modelled the nonlinear error for the z-axis gyroscope while the GPS signal was available. During a GPS outage, the PCI nonlinear error model was combined with the KF estimated error and the mechanization error, to provide a corrected azimuth. The KFPCI algorithm showed an improvement over the KF algorithm in RMS position error, maximum position error, RMS azimuth error, and maximum azimuth error by an average of 30.76%, 34.71%, 66.76%, and 53.58% in each of the respective areas. / Thesis (Master, Electrical & Computer Engineering) -- Queen's University, 2013-06-11 18:13:12.625

Pyrrolidine and pyrrolidinone rings are common motifs found in many biologically active natural products and drugs. Accordingly, our work focuses on the development of new methodologies for their one-pot synthesis. An efficient diastereoselective nitro-Mannich / lactamisation reaction cascade of methyl 3-nitropropanoate with cyclic and acyclic imines for the direct preparation of trans-monocyclic and fused tricyclic pyrrolidinone derivatives was developed. The reaction is easy to perform, broad in scope and tolerates a wide variety of functional groups. For the monocyclic methodology, 28 examples with a very good average yield of 72% and excellent diastereocontrol (typical dr >98:2) were obtained using optimized conditions and varying the amine and the aldehyde reagents. The methodology has been extended to the synthesis of 1,3,5-trisubstituted 4-nitropyrrolidinone derivatives using α-substituted 3-nitropropanoate. Using a one-pot protocol, 22 derivatives were synthesised in good yields (65% average) and diastereomeric ratios ranging from 3:1 to 30:1 in favor of the trans/trans diastereoisomer. In addition, the nitro-Mannich / lactamisation cascade of methyl 3-nitropropanoate was developed further to allow the rapid synthesis of 5-isopropyl-4-nitropyrrolidin-2-one from reaction with ammonium acetate and 1-butyl-4-nitropyrrolidin-2-one from reaction with formaldehyde. Also, the synthetic utility of the nitro-pyrrolidinones formed was exemplified through various functional group modifications: the selective reduction of the lactam carbonyl, the reduction of the nitro group in the presence or absence of a carbonyl group and the reductive removal of the nitro group. The development of an enantioselective version of the cascade under chiral Brönsted acid catalysis provided promising results (up to 90% ee). Moreover, various studies were undertaken to understand the mechanism of the reaction and the nitro-Mannich / latamisation cascade is now well understood. Furthermore, a formal synthesis of rac-Slaframine in 8 steps and 15% overall yield was achieved and it inspired additional work towards a nitro-Mannich / epoxide ring opening cascade.

The objective of a coating operation is to transfer a defect free liquid film onto a continuous substrate in order to meet the requirements of the final products. Mainly two concerns govern the process. The first concern is the economics of the process and the second concern is the quality of the coated film. The economics of the process are dictated by the speed of coating and the film thickness. Clearly, higher speeds mean better productivity hence less cost of operation and thinner films are desirable because less material is being used. Quality is governed by film uniformity and integrity, indicating that the film will perform as designed. Film defects such as streaks or tiny air bubbles are indication that the film properties are not uniform rendering it unacceptable to customers. One of the most versatile coating systems to achieve thin films at high speeds is reverse roll coating which has been used for a long time all over the world. At low speed, typically 1m/s, this coating operation is inherently stable and with small gaps of order 100 microns can ii lead to film thickness of order 30-50 microns. Much research, theoretical and experimental, has been devoted to this coating flow but only at low speeds and for large gaps (>100 microns). There are no comprehensive data how very thin films, 20 microns and less (particularly lower limits in the region of 5 microns) can be achieved at high speeds, of 2 or more metres per second. This study is concerned precisely with this aim, that of investigating the effect of large speeds and small roller gaps (rollers nearly touching or in elastohydrodynamic contact) to achieve the very thin films desired by modern applications (electronics, medical and others). In order to achieve this aim, a rig was designed and built to enable to understand the effect of various coating conditions and liquid properties on the metered film thickness and coating instability. To achieve thin films at high speeds, small roll gap and low viscosity are needed, however flow instabilities will develop under these conditions. To achieve stable coating window at high speeds high surface tension is needed. It was found that the roll gap and the viscosity have complicated effect on the coating window. In the case of low viscosity liquid (7mPa.s), small roll gaps are needed, whereas in the case of high viscosity liquid (more than 30mPa.s), large gaps are needed. It was found that Weber number is better describer for ribbing instability in rigid reverse roll coating unlike in rigid forward roll coating in which capillary number is the one. In addition the potential of reverse deformable roll coating (rolls in elastohydrodynamic contact) was investigated in order to achieve much thinner films at higher speeds. As a result of the investigation of reverse deformable roll coating, it was found that there is a possibility to get much thinner stable films at much higher speeds compared to reverse rigid roll coating. The liquid transfer from an applicator roller to a PET film was investigated in this study. It was found that air stagnation at downstream meniscus and air entrainment at upstream meniscus depend on the liquid properties such as viscosity and surface tension and coating conditions such as web tension and wrap angle of web. As a result, wet film instability also depends on liquid properties and coating conditions. It was found that air stagnation causes streaks on the wet film and air entrainment caused bubbles on the wet film. To get a stable wet film, it was found that suitable viscosity and high surface tension were needed.

Cascade impactors, routinely used for in vitro particle size characterization of pharmaceutical aerosols, are calibrated using dilute, charge-neutralized, monodisperse aerosols. But pharmaceutical aerosols are known to generate concentrated, inherently charged, polydisperse aerosol clouds. A computational model of the Andersen Cascade Impactor (ACI) suggested that the presence of charge on aerosol particles may influence their deposition within the ACI, but experimental validation of the model is warranted. This dissertation investigates the influence of electrostatic charge upon the deposition behavior of aerosols within cascade impactors, to address the impact of charge on particle size characterization. The influence of applied charge upon the deposition pattern and aerodynamic particle size distribution (APSD) of commercially available pressurized metered dose inhalers (pMDIs) within the Electrical Low Pressure Impactor (ELPI) was examined. Electrostatic properties were modified using an external voltage source in conjunction with the ELPI corona charger and observed to be dependent on the formulation and device packaging. Induced artificial charge on the aerosol particles influenced the deposition pattern within the impactor, but did not result in a significant change in the apparent APSD. An experimental apparatus capable of producing charge neutralized and charged aerosol, with targeted deposition on the CFD predicted ‘charge sensitive’ ACI stages, was developed. In vitro results were observed to be in partial agreement with the CFD predictions. While charge influenced the deposition pattern in the ACI with increased deposition observed in the charger and on the upper stages of the ACI, it did not influence the apparent APSD of the aerosol. Electrostatic charge effects on deposition behavior within cascade impactors were delineated with respect to space charge and image charge effects by investigating the influence of impactor grounding, particle size, stage coating and loading. While the deposition pattern within the ACI was influenced by charge, only stage coating and stage loading resulted in a small, significant difference in the apparent APSD, which may not be practically relevant due to the variability associated with in vitro aerosol testing. Similar trends were observed in the deposition behavior of charge neutralized and charged aerosol within an abbreviated ACI system compared to the full resolution ACI.

A computer model for a general clarifier-thickener has been made and used for comparing different strategies for control of such dewatering units through simulations. The model builds on widely acknowledged theory for modelling clarifier-thickeners - discretizing the settling PDE into a set of ODEs so that concentrations of solids at discrete depths inside the unit become the states of the numerical model - and it was written in the Modelica language using the modelling and simulation environment Dymola. The work of estimating model parameters for themodel and comparing different control strategies was made looking at one particular clarifier-thickener at the company Boliden's mineral processing plant in Garpenberg. Among the control strategies that were compared in simulations were simple PID control and cascade control as well as more advanced control schemes. The simulations showed that the optimal control strategy to use is cascade control using rake torque as a secondary variable, which makes sense in particular for large thickeners such as the one mainly considered in this work.

The research in this thesis describes an asymmetric pericyclic cascade approach to the synthesis of a range of enantioenriched oxindoles using enantiopure oxazolidine derived nitrones and disubstituted ketenes. Chapter 1 aims to place this work in the context of the literature, describing other commonly employed or state-of-the-art asymmetric approaches to oxindoles and related compounds. Examples of where these approaches have been used successfully in the total synthesis of related indole alkaloids are also presented. The conception of this project within the group is also described alongside initial attempts to develop the first enantioselective variant of the same reaction using nitrone chiral auxiliaries. Chapter 2 details the optimisation of this asymmetric oxindole forming reaction by structural variation of the nitrone component, culminating in the preparation of an N-TIPBS nitrone based on an oxazolidine framework, which proved to be optimal for this process. Also detailed are attempts to gain insight towards the mechanism of this transformation and to understand the mode of chirality transfer. Chapter 3 details the use of the N-TIPBS nitrone scaffold as a transmitter of chiral information in the synthesis of 3-alkyl-3-aryloxindoles and spirocyclic oxindoles. Chapter 4 delineates the mechanism of this transformation as a pericyclic cascade process. The key stereo-determining features are discussed including the conformational preferences of such chiral oxazolidine derived nitrones and the influence of the N-protecting group on the stereochemical outcome. Synthetic endeavours to provide evidence as to the validity of this computational mechanistic rationale are also presented. Chapter 5 describes regioselectivity studies, and tolerance of both the racemic and asymmetric reactions to varying substitution on the nitrone N-aryl ring. Initial studies were undertaken using achiral nitrones before the interplay between regio- and stereoselectivity was explored, initially with enantiopure N-Boc Garner's aldehyde derived nitrones, and further with N-TIPBS nitrones. Chapter 6 initially describes attempts to transform this chiral auxiliary methodology into a catalytic asymmetric protocol, by investigating in situ ketene formation via various strategies including activation of carboxylic acids. Also described are investigations into related nitrone-ketenimine cycloadditions, and related [3+2] nitrone cycloadditions. Chapter 7 describes the application of this methodology toward the synthesis of compounds with biological relevance. The concise asymmetric synthesis of a Roche anti-cancer agent is outlined, as is the extension of this methodology to the synthesis of indole alkaloid-like species. Finally, the attempted application of this methodology toward the asymmetric synthesis of (+)-gliocladin C is outlined.

Leptospiras são bactérias espiroquetas altamente móveis dotadas de estratégias que possibilitam grande eficiência nos processos de invasão e disseminação no hospedeiro. Nosso grupo demonstrou previamente que leptospiras patogênicas secretam proteases capazes de clivar e inativar moléculas-chave do sistema complemento humano, o que confere a essas bactérias a capacidade de driblar os mecanismos de defesa do sistema imune inato. Dada a rápida disseminação das leptospiras durante o processo de infecção, aventou-se a hipótese de que essas proteases secretadas pudessem alvejar uma gama maior de moléculas do hospedeiro. No presente estudo, a atividade proteolítica de proteínas secretadas por leptospiras sobre um painel de moléculas da matriz extracelular e do plasma foi avaliada. O sobrenadante de cultura da estirpe virulenta L. interrogans sorovar Kennewicki Fromm degradou fibrinogênio humano, fibronectina plasmática, colágeno Tipo I, e as proteoglicanas decorina, biglicam e lumicam. A atividade proteolítica foi inibida por 1,10-fenantrolina, sugerindo o envolvimento de metaloproteases. Laminina, matrigel, plasminogênio e trombina não foram clivados por proteases presentes nos sobrenadantes. Ainda, os dados indicam que a produção de proteases deve ser um determinante de virulência importante, uma vez que os sobrenadantes de estirpes saprófitas ou patogênicas atenuadas em cultura não apresentaram atividade proteolítica sobre componentes da matriz ou do plasma. A análise dos genomas de leptospiras disponíveis nos levou à identificação de quatro termolisinas, metaloproteases presentes apenas nas espécies patogênicas. Uma delas, codificada pele LIC13322, foi produzida na forma recombinante e apresentou atividade proteolítica sobre fibrinogênio, biglicam e decorina. Em paralelo, foram também realizadas análises comparativas dos exoproteomas das estirpes Fromm e Patoc I. Algumas metaloproteases que podem estar envolvidas na degradação de moléculas do hospedeiro foram identificadas. A capacidade de clivar moléculas do tecido conjuntivo e proteínas da cascata de coagulação pode certamente contribuir para a invasão e a destruição tecidual observadas durante a infecção por Leptospira. / Leptospires are highly motile spirochetes equipped with strategies for efficient invasion and dissemination within the host. Our group previously demonstrated that pathogenic leptospires secrete proteases capable of cleaving and inactivating key molecules of the human complement system, allowing these bacteria to circumvent host´s innate immune defense mechanisms. Given the successful dissemination of leptospires during infection, we wondered if such proteases would target a broader range of host molecules. In the present study, the proteolytic activity of secreted leptospiral proteases against a panel of extracellular matrix and plasma proteins was assessed. The culture supernatant of the virulent L. interrogans serovar Kennewicki strain Fromm degraded human fibrinogen, plasma fibronectin, collagen Type 1, and the proteoglycans decorin, biglycan, and lumican. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. Laminin, matrigel, plasminogen and thrombin were not cleaved by proteases present in the supernatants. Moreover, production of proteases might be an important virulence determinant since culture-attenuated or saprophytic Leptospira did not display proteolytic acticity against ECM or plasma components. A search against Leptospira genomes allowed identification of four thermolysins, which are metalloproteases found exclusively in pathogenic species. One of them, encoded by LIC13322, was produced in the recombinant form and displayed proteolytic activity against fibrinogen, biglycan and decorin. Comparative exoproteomic analyses using Fromm and Patoc I strains were also performed and allowed identification of a few metalloproteases that could be involved in the degradation of host components. The ability to cleave connective tissue molecules and coagulation cascade proteins may certainly contribute to invasion and tissue destruction observed upon infection with Leptospira.