We develop and adapt absolute stability results for nonnegative Lur'e systems, that is, systems made up of linear part and a nonlinear feedback in which the state remains nonnegative for all time. This is done in both continuous and discrete time with an aim of applying these results to population modeling. Further to this, we consider forced nonnegative Lur'e systems, that is, Lur'e systems with an additional disturbance, and provide results on input-to-state stability (ISS), again in both continuous and discrete time. We provide necessary and sufficient conditions for a forced Lur'e system to have the converging-input converging-state (CICS) property in a general setting before specializing these results to nonnegative, single-input, single-output systems. Finally we apply integral control to nonnegative systems in order to control the output of the system with the key focus being on applications to population management.

O presente trabalho teve como objetivo o estudo do estado sólido do ganciclovir (GCV) e suas diferentes formas polimórficas. O GCV é um fármaco antiviral útil no tratamento de infecções por citomegalovírus (CMV). Embora seja um fármaco amplamente usado, poucos estudos têm sido realizados sobre seu estado sólido. Atualmente, o GCV é conhecido por apresentar quatro formas cristalinas, duas anidras (Forma I e II) e duas hidratas (III e IV). Neste trabalho, nós reportamos a solução da estrutura cristalográfica da Forma I do GCV, que foi encontrado durante o screening de cristalização do fármaco, em que nove ensaios de cristalização (GCV-1, GCV-A, GCV-B, GCV-C, GCV-D, GCV-E, GCV-F, GCV-G e GCV-H) foram realizados e os materiais resultantes foram caracterizados por Difratometria de raios X (DRX), análise térmica (DTA/TG) e Hot Stage Microscopy. De todas as cristalizações realizadas foram obtidas quatro formas sólidas, denominadas como Forma I (GCV-1, GCV-B e GCV-H), Forma III (GCV-C, GCV-D, GCV-F e GCV-G), Forma IV (GCV-A) e Forma V (GCV-E). Esta última está sendo descrita pela primeira vez na literatura e indica a presença de outra forma hidratada de GCV. As Formas I, III e IV corresponderam a forma anidra e as duas formas hidratadas do fármaco, respectivamente. Além disso, foi evidenciado por experimentos de conversão de slurry e análise térmica que o cristalizado de GCV-1 (Forma I) foi o mais estável entre os materiais obtidos, e este deu origem ao monocristal da Forma I de GCV, estrutura cristalina anidra do fármaco. Neste trabalho, pela primeira vez, a estrutura cristalina deste composto foi definida por cristalografia de raios X de monocristal. A análise estrutural mostrou que a Forma I do fármaco cristaliza no grupo espacial monoclínico P21/c e está composta por quatro moléculas de GCV na sua unidade assimétrica. Cada molécula está unida intermolecularmente por ligações de hidrogênio, que dão lugar à formação de cadeias infinitas e estas por sua vez se arranjam de maneira a formar uma estrutura tridimensional. / This presented work aims to study the solid state of ganciclovir (GCV) and its different polymorphic forms. GCV is an antiviral drug useful in the treatment of cytomegalovirus (CMV) infections. Although it is a widely-used drug, few studies have been conducted on its solid state. Currently, GCV is known to have four crystalline forms, two anhydrous (Form I and II) and two hydrates (III and IV). In this investigation, we report a successful preparation of GCV Form I and its crystallographic structure, which was found during the crystallization of the drug, in which nine crystallization tests (GCV-1, GCV-A, GCV-B, GCV- D, GCV-E, GCV-F, GCV-G and GCV-H) were performed and the resulting materials were characterized by X-ray diffractometry (XRD), thermal analysis (DTA/TG) and Hot Stage Microscopy. Of all the crystallizations performed, four solid forms were obtained, denoted as Form I (GCV-1, GCV-B and GCV- H), Form III (GCV-C, GCV-D, GCV-F and GCV-G), Form IV (GCV-A) and Form V (GCV-E). The latter is being described for the first time in the literature and indicates the presence of another hydrated form of GCV. Forms I, III and IV corresponded to the anhydrous form and the two hydrated forms of the drug, respectively. In addition, it was evident by both the slurry conversion and the thermal analysis methods that the GCV-1 crystallized (Form I) was indeed the most stable amongst the materials obtained. This gave rise to GCV Form I monocrystal, anhydrous crystalline structure of the drug. The compound was characterized by monocrystal X-ray crystallography. The structural analysis showed that Form I of the drug crystallized in the monoclinic system space group P21/c is composed of four molecules of GCV in its asymmetric unit. Each molecule is linked intermolecularly by hydrogen bonds, which give rise to the formation of infinite chains arranged in a way that form a three-dimensional structure.

O presente trabalho teve como objetivo o estudo do estado sólido do ganciclovir (GCV) e suas diferentes formas polimórficas. O GCV é um fármaco antiviral útil no tratamento de infecções por citomegalovírus (CMV). Embora seja um fármaco amplamente usado, poucos estudos têm sido realizados sobre seu estado sólido. Atualmente, o GCV é conhecido por apresentar quatro formas cristalinas, duas anidras (Forma I e II) e duas hidratas (III e IV). Neste trabalho, nós reportamos a solução da estrutura cristalográfica da Forma I do GCV, que foi encontrado durante o screening de cristalização do fármaco, em que nove ensaios de cristalização (GCV-1, GCV-A, GCV-B, GCV-C, GCV-D, GCV-E, GCV-F, GCV-G e GCV-H) foram realizados e os materiais resultantes foram caracterizados por Difratometria de raios X (DRX), análise térmica (DTA/TG) e Hot Stage Microscopy. De todas as cristalizações realizadas foram obtidas quatro formas sólidas, denominadas como Forma I (GCV-1, GCV-B e GCV-H), Forma III (GCV-C, GCV-D, GCV-F e GCV-G), Forma IV (GCV-A) e Forma V (GCV-E). Esta última está sendo descrita pela primeira vez na literatura e indica a presença de outra forma hidratada de GCV. As Formas I, III e IV corresponderam a forma anidra e as duas formas hidratadas do fármaco, respectivamente. Além disso, foi evidenciado por experimentos de conversão de slurry e análise térmica que o cristalizado de GCV-1 (Forma I) foi o mais estável entre os materiais obtidos, e este deu origem ao monocristal da Forma I de GCV, estrutura cristalina anidra do fármaco. Neste trabalho, pela primeira vez, a estrutura cristalina deste composto foi definida por cristalografia de raios X de monocristal. A análise estrutural mostrou que a Forma I do fármaco cristaliza no grupo espacial monoclínico P21/c e está composta por quatro moléculas de GCV na sua unidade assimétrica. Cada molécula está unida intermolecularmente por ligações de hidrogênio, que dão lugar à formação de cadeias infinitas e estas por sua vez se arranjam de maneira a formar uma estrutura tridimensional. / This presented work aims to study the solid state of ganciclovir (GCV) and its different polymorphic forms. GCV is an antiviral drug useful in the treatment of cytomegalovirus (CMV) infections. Although it is a widely-used drug, few studies have been conducted on its solid state. Currently, GCV is known to have four crystalline forms, two anhydrous (Form I and II) and two hydrates (III and IV). In this investigation, we report a successful preparation of GCV Form I and its crystallographic structure, which was found during the crystallization of the drug, in which nine crystallization tests (GCV-1, GCV-A, GCV-B, GCV- D, GCV-E, GCV-F, GCV-G and GCV-H) were performed and the resulting materials were characterized by X-ray diffractometry (XRD), thermal analysis (DTA/TG) and Hot Stage Microscopy. Of all the crystallizations performed, four solid forms were obtained, denoted as Form I (GCV-1, GCV-B and GCV- H), Form III (GCV-C, GCV-D, GCV-F and GCV-G), Form IV (GCV-A) and Form V (GCV-E). The latter is being described for the first time in the literature and indicates the presence of another hydrated form of GCV. Forms I, III and IV corresponded to the anhydrous form and the two hydrated forms of the drug, respectively. In addition, it was evident by both the slurry conversion and the thermal analysis methods that the GCV-1 crystallized (Form I) was indeed the most stable amongst the materials obtained. This gave rise to GCV Form I monocrystal, anhydrous crystalline structure of the drug. The compound was characterized by monocrystal X-ray crystallography. The structural analysis showed that Form I of the drug crystallized in the monoclinic system space group P21/c is composed of four molecules of GCV in its asymmetric unit. Each molecule is linked intermolecularly by hydrogen bonds, which give rise to the formation of infinite chains arranged in a way that form a three-dimensional structure.

No description available.

Asymptotic stability is a key notion of system stability for controlled dynamical systems as it guarantees that the system trajectories are bounded in a neighborhood of a given isolated equilibrium point and converge to this equilibrium over the infinite horizon. In some applications, however, asymptotic stability is not the appropriate notion of stability. For example, for systems with a continuum of equilibria, every neighborhood of an equilibrium contains another equilibrium and a nonisolated equilibrium cannot be asymptotically stable. Alternatively, in stabilization of spacecraft dynamics via gimballed gyroscopes, it is desirable to find state- and output-feedback control laws that guarantee partial-state stability of the closed-loop system, that is, stability with respect to part of the system state. Furthermore, we may additionally require finite-time stability of the closed-loop system, that is, convergence of the system's trajectories to a Lyapunov stable equilibrium in finite time. The Hamilton-Jacobi-Bellman optimal control framework provides necessary and sufficient conditions for the existence of state-feedback controllers that minimize a given performance measure and guarantee asymptotic stability of the closed-loop system. In this research, we provide extensions of the Hamilton-Jacobi-Bellman optimal control theory to develop state-feedback control laws that minimize nonlinear-nonquadratic performance criteria and guarantee semistability, partial-state stability, finite-time stability, and finite-time partial state stability of the closed-loop system.

Lebanon has historically been at the center of Middle Eastern conflict. Religious diversity and weak institutions have resulted in the country’s continual exploitation by powerful foreign states. At first, a historical overview of Lebanon demonstrates how certain events over the past 200 years have shaped the country. Based on recurring political and economic misfortunes, sectarian tensions within Lebanon have flared since the dissolution of the Ottoman Empire. This thesis argues that in order to stabilize the country and prevent the meddling of foreign powers, a focus must be placed on establishing a national identity, strengthening the country’s political institutions, and creating an accountable economic system.

<p>Antibody-drug conjugates (ADCs) combine the cytotoxicity of traditional chemotherapy with the site-specificity of antibodies by conjugating payloads to antibodies with immunoaffinity. However, the conjugation alters the physicochemical properties of antibodies, increasing the risks of various types of degradation. The effects of common risk factors such as pH, temperature, and light on the stability of ADCs differ from their effects on monoclonal antibodies (mAb) due to these altered physicochemical properties. </p> <p>To date, ADC researchers have developed linkers with improved <i>in vivo</i> stability, and begun to understand the deconjugation mechanisms <i>in vivo</i>. In contrast, the <i>in vitro</i> stability of ADCs has not gained comparable attention. All nine of the U.S. FDA approved ADCs are lyophilized to minimize the potential for degradation. However, there are few studies on the solid-state stability of ADCs. To evaluate lyophilized solids, pharmaceutical development relies heavily on accelerated stability studies, which take months to determine the best formulation. Characterization methods that are often used orthogonally with accelerated studies include Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, near-infrared spectroscopy (NIR), differential scanning calorimetry (DSC), and x-ray powder diffraction (XRPD). Results from these methods are often poorly correlated with stability, however. Thus, stability evaluation of solid-state ADC products, and other recombinant protein drugs, is often a bottleneck in their development.</p> <p>To provide knowledge on how to improve the <i>in vitro</i> stability of lyophilized ADC formulations, the solid-state stability of ADC formulations with varying risk factors was studied in this dissertation project. The first study investigated interactions between an ADC and excipients in terms of solid-state stability enhancement. The second study investigated the process-driven instability of ADCs during lyophilization using various concentrations of ADCs. The first two studies incorporate a new method called solid-state hydrogen/deuterium exchange coupled with mass spectrometry (ssHDX-MS) as an analytical predictor of solid-state stability. The last study investigated the effects of pH on the stability of labile hydrazones, as a model for common linker chemistry used in ADCs. </p>

Cette thèse porte sur l’amélioration du laminage à chaud, un procédé de fabrication sidérurgique permettant de transformer une brame de métal (10m de long, 1.5m de large et 250mm d’épaisseur) en une bande de tôle bobinée (1000m de long, 1m de large et 2mm d’épaisseur). Afin d’obtenir certaines propriétés mécaniques et de faciliter la phase de laminage, la brame est réchauffée à 1300°C et dégrossi avant d’être envoyé vers le train finisseur où elle est laminée en passant successivement dans plusieurs cages (ensemble de cylindres qui écrasent le métal) et qui permettent de réduire l’épaisseur à la valeur finale souhaitée. Le produit est finalement refroidi puis bobiné avant d’être envoyé au client. La thèse se focalise sur l’amélioration du train finisseur en proposant un contrôle du frottement entre la bande et les cylindres de travail à l’aide d’une lubrification. La lubrification consiste à déposer de l’huile sur le cylindre en vaporisant une émulsion d’eau et d’huile. L’huile déposée modifie l’interface entre la bande et le cylindre et diminue le coefficient de frottement. Cette diminution du coefficient de frottement a plusieurs avantages : elle permet de réduire l’usure des cylindres, d’améliorer l’état de surface de la bande, de réduire l’effort nécessaire de laminage donc la consommation d’énergie et d’augmenter la capacité du train. A l’inverse, un frottement trop bas dû à une lubrification trop importante peut causer un patinage de la bande entrainant l’arrêt du train. Il est donc important de contrôler le niveau de frottement de manière sécurisée. La conception du contrôle s’est faite à travers deux principales étapes : La modélisation et l’identification de l’effet de la lubrification sur le coefficient de frottement, la conception du contrôle du frottement / This thesis is about the improvement of the hot rolling process. This steelmaking process turns a slab (10m long, 1.5m wide, 250mm thick) into a coiled strip (1000m long, 1m wide, 2mm thick). To obtain some metallurgical properties and to make the rolling easier, the slab is heated up to 1300 ° C and roughly rolled before going to the finishing mill. In the finishing mill the strip is rolled through successive stands (set of rolls) to reduce the thickness to its final desired value. The product is finally cooled down and coiled before shipping it to the customers. The thesis focuses on the enhancement of the finishing mill through a friction control between the strip and the work rolls using lubrication. The lubrication consists in building up oil on the rolls by spraying an emulsion of water and oil. The deposited oil changes the contact interface between the strip and the roll and decreases the friction coefficient. The reduction of the friction presents the advantages of: reduce the roll wear, enhance the strip surface quality, decrease the rolling force (reduce then the energy consumption) and increase the mill capability. In the other hand, an insufficient amount of friction due to an overabundance of lubrication can induce a slippage of the strip leading to a stop of the mill. It is important to control the amount of friction in a secure way. The design of the controller was done through two main steps: Modeling and identification of the effect of lubrication on the friction coefficient, designing the friction control

A hybrid system is a dynamical system that exhibits both continuous and discrete dynamic behavior. Hybrid systems arise in a wide variety of important applications in diverse areas, ranging from biology to computer science to air traffic dynamics. The interaction of continuous- and discrete-time dynamics in a hybrid system often leads to very rich dynamical behavior and phenomena that are not encountered in purely continuous- or discrete-time systems. Investigating the dynamical behavior of hybrid systems is of great theoretical and practical importance. The objectives of this thesis are to develop the qualitative theory of nonlinear hybrid systems with impulses, time-delay, switching modes, and stochastic disturbances, to develop algorithms and perform analysis for hybrid systems with an emphasis on stability and control, and to apply the theory and methods to real-world application problems. Switched nonlinear systems are formulated as a family of nonlinear differential equations, called subsystems, together with a switching signal that selects the continuous dynamics among the subsystems. Uniform stability is studied emphasizing the situation where both stable and unstable subsystems are present. Uniformity of stability refers to both the initial time and a family of switching signals. Stabilization of nonlinear systems via state-dependent switching signal is investigated. Based on assumptions on a convex linear combination of the nonlinear vector fields, a generalized minimal rule is proposed to generate stabilizing switching signals that are well-defined and do not exhibit chattering or Zeno behavior. Impulsive switched systems are hybrid systems exhibiting both impulse and switching effects, and are mathematically formulated as a switched nonlinear system coupled with a sequence of nonlinear difference equations that act on the switched system at discrete times. Impulsive switching signals integrate both impulsive and switching laws that specify when and how impulses and switching occur. Invariance principles can be used to investigate asymptotic stability in the absence of a strict Lyapunov function. An invariance principle is established for impulsive switched systems under weak dwell-time signals. Applications of this invariance principle provide several asymptotic stability criteria. Input-to-state stability notions are formulated in terms of two different measures, which not only unify various stability notions under the stability theory in two measures, but also bridge this theory with the existent input/output theories for nonlinear systems. Input-to-state stability results are obtained for impulsive switched systems under generalized dwell-time signals. Hybrid time-delay systems are hybrid systems with dependence on the past states of the systems. Switched delay systems and impulsive switched systems are special classes of hybrid time-delay systems. Both invariance property and input-to-state stability are extended to cover hybrid time-delay systems. Stochastic hybrid systems are hybrid systems subject to random disturbances, and are formulated using stochastic differential equations. Focused on stochastic hybrid systems with time-delay, a fundamental theory regarding existence and uniqueness of solutions is established. Stabilization schemes for stochastic delay systems using state-dependent switching and stabilizing impulses are proposed, both emphasizing the situation where all the subsystems are unstable. Concerning general stochastic hybrid systems with time-delay, the Razumikhin technique and multiple Lyapunov functions are combined to obtain several Razumikhin-type theorems on both moment and almost sure stability of stochastic hybrid systems with time-delay. Consensus problems in networked multi-agent systems and global convergence of artificial neural networks are related to qualitative studies of hybrid systems in the sense that dynamic switching, impulsive effects, communication time-delays, and random disturbances are ubiquitous in networked systems. Consensus protocols are proposed for reaching consensus among networked agents despite switching network topologies, communication time-delays, and measurement noises. Focused on neural networks with discontinuous neuron activation functions and mixed time-delays, sufficient conditions for existence and uniqueness of equilibrium and global convergence and stability are derived using both linear matrix inequalities and M-matrix type conditions. Numerical examples and simulations are presented throughout this thesis to illustrate the theoretical results.

A hybrid system is a dynamical system that exhibits both continuous and discrete dynamic behavior. Hybrid systems arise in a wide variety of important applications in diverse areas, ranging from biology to computer science to air traffic dynamics. The interaction of continuous- and discrete-time dynamics in a hybrid system often leads to very rich dynamical behavior and phenomena that are not encountered in purely continuous- or discrete-time systems. Investigating the dynamical behavior of hybrid systems is of great theoretical and practical importance. The objectives of this thesis are to develop the qualitative theory of nonlinear hybrid systems with impulses, time-delay, switching modes, and stochastic disturbances, to develop algorithms and perform analysis for hybrid systems with an emphasis on stability and control, and to apply the theory and methods to real-world application problems. Switched nonlinear systems are formulated as a family of nonlinear differential equations, called subsystems, together with a switching signal that selects the continuous dynamics among the subsystems. Uniform stability is studied emphasizing the situation where both stable and unstable subsystems are present. Uniformity of stability refers to both the initial time and a family of switching signals. Stabilization of nonlinear systems via state-dependent switching signal is investigated. Based on assumptions on a convex linear combination of the nonlinear vector fields, a generalized minimal rule is proposed to generate stabilizing switching signals that are well-defined and do not exhibit chattering or Zeno behavior. Impulsive switched systems are hybrid systems exhibiting both impulse and switching effects, and are mathematically formulated as a switched nonlinear system coupled with a sequence of nonlinear difference equations that act on the switched system at discrete times. Impulsive switching signals integrate both impulsive and switching laws that specify when and how impulses and switching occur. Invariance principles can be used to investigate asymptotic stability in the absence of a strict Lyapunov function. An invariance principle is established for impulsive switched systems under weak dwell-time signals. Applications of this invariance principle provide several asymptotic stability criteria. Input-to-state stability notions are formulated in terms of two different measures, which not only unify various stability notions under the stability theory in two measures, but also bridge this theory with the existent input/output theories for nonlinear systems. Input-to-state stability results are obtained for impulsive switched systems under generalized dwell-time signals. Hybrid time-delay systems are hybrid systems with dependence on the past states of the systems. Switched delay systems and impulsive switched systems are special classes of hybrid time-delay systems. Both invariance property and input-to-state stability are extended to cover hybrid time-delay systems. Stochastic hybrid systems are hybrid systems subject to random disturbances, and are formulated using stochastic differential equations. Focused on stochastic hybrid systems with time-delay, a fundamental theory regarding existence and uniqueness of solutions is established. Stabilization schemes for stochastic delay systems using state-dependent switching and stabilizing impulses are proposed, both emphasizing the situation where all the subsystems are unstable. Concerning general stochastic hybrid systems with time-delay, the Razumikhin technique and multiple Lyapunov functions are combined to obtain several Razumikhin-type theorems on both moment and almost sure stability of stochastic hybrid systems with time-delay. Consensus problems in networked multi-agent systems and global convergence of artificial neural networks are related to qualitative studies of hybrid systems in the sense that dynamic switching, impulsive effects, communication time-delays, and random disturbances are ubiquitous in networked systems. Consensus protocols are proposed for reaching consensus among networked agents despite switching network topologies, communication time-delays, and measurement noises. Focused on neural networks with discontinuous neuron activation functions and mixed time-delays, sufficient conditions for existence and uniqueness of equilibrium and global convergence and stability are derived using both linear matrix inequalities and M-matrix type conditions. Numerical examples and simulations are presented throughout this thesis to illustrate the theoretical results.