Cyber-physical systems (CPSs) tightly integrate physical processes with computing and communication to autonomously interact with the surrounding environment.This enables emerging applications such as autonomous driving, coordinated flightof swarms of drones, or smart factories. However, current technology does notprovide the reliability and flexibility to realize those applications. Challenges arisefrom wireless communication between the agents and from the complexity of thesystem dynamics. In this thesis, we take on these challenges and present three maincontributions.We first consider imperfections inherent in wireless networks, such as communication delays and message losses, through a tight co-design. We tame the imperfectionsto the extent possible and address the remaining uncertainties with a suitable controldesign. That way, we can guarantee stability of the overall system and demonstratefeedback control over a wireless multi-hop network at update rates of 20-50 ms.If multiple agents use the same wireless network in a wireless CPS, limitedbandwidth is a particular challenge. In our second contribution, we present aframework that allows agents to predict their future communication needs. Thisallows the network to schedule resources to agents that are in need of communication.In this way, the limited resource communication can be used in an efficient manner.As a third contribution, to increase the flexibility of designs, we introduce machinelearning techniques. We present two different approaches. In the first approach,we enable systems to automatically learn their system dynamics in case the truedynamics diverge from the available model. Thus, we get rid of the assumption ofhaving an accurate system model available for all agents. In the second approach, wepropose a framework to directly learn actuation strategies that respect bandwidthconstraints. Such approaches are completely independent of a system model andstraightforwardly extend to nonlinear settings. Therefore, they are also suitable forapplications with complex system dynamics. / <p>QC 20190118</p>

Greenhouse environments often promote bacterial and fungal infections in important crop plants. Exogenous application of chemical inducers could help reduce the severity of infection, or even prevent infection. Small molecules such as glycerol, azelaic acid and pipecolic acid have been implicated as being important signaling molecules during Systemic Acquired Resistance (SAR). To examine if these small molecules could be used to induce resistance in crop plants, exogenous treatment assays were developed in cucumber. Glycerol spray and azelaic acid infiltration induced modest resistance at locally treated leaves. Pipecolic acid soil treatment induced modest resistance in aerial tissue of cucumber plants, and strong resistance when plants were treated weekly. This knowledge may be useful in promoting the commercialization of SAR-associated compounds to protect important crop plants against disease. Plants possess multiple defense pathways that include an SA signaling component to initiate resistance to microbial pathogens. However, during Age-Related Resistance (ARR) in Arabidopsis, a number of studies support that SA acts as an anti-microbial and anti-biofilm agent against Pseudomonas syringae pv. tomato (Pst) in the plant intercellular space. Little is known about the role of Pst biofilm formation during infection of young plants or if other defense responses act to suppress bacterial biofilm formation. Therefore Pst biofilm formation and the effect of PAMP Triggered Immunity (PTI) on bacterial biofilm formation was examined. PTI was induced with flg22 in wild-type Col-0, fls2, bak1-3 (PTI mutants) and sid2-2 (SA biosynthesis mutant). In vivo bacterial biofilm-like aggregate formation was monitored using Pst DC3000 PDSK-GFPuv and epifluorescence microscopy. Pst aggregate occurrence and size were positively correlated with bacterial success in susceptible plants (wild-type Col-0, fls2, bak1-3, sid2-2), while fewer and smaller bacterial aggregates were observed in Col-0 undergoing PTI. To determine if the extracellular polysaccharide, alginate was a major contributor to biofilm formation, in vivo bacterial aggregate formation was monitored using alginate deficient Pst-GFP. Alginate deficient Pst-GFP and wild-type Pst grew to similar levels in wild-type plants suggesting that the ability to produce alginate was not necessary for Pst pathogenicity and success in planta. Fewer alginate-deficient Pst aggregates were observed compared to wild-type Pst in inoculated plants, suggesting that the ability to produce alginate was modestly important for aggregate formation. These data provide novel insights into how biofilms form in planta, the association between pathogen virulence and biofilm formation, and how plant defense responses such as PTI not only reduce bacterial growth, but also target biofilms. / Thesis / Master of Science (MSc)

In this dissertation, we study multi-robot coordination in the context of multi-target tracking. Specifically, we are interested in the coordination achieved by means of submodular function optimization. Submodularity encodes the diminishing returns property that arises in multi-robot coordination. For example, the marginal gain of assigning an additional robot to track the same target diminishes as the number of robots assigned increases. The advantage of formulating coordination problems as submodular optimization is that a simple, greedy algorithm is guaranteed to give a good performance. However, often this comes at the expense of unrealistic models and assumptions. For example, the standard formulation does not take into account the fact that robots may fail, either randomly or due to adversarial attacks. When operating in uncertain conditions, we typically seek to optimize the expected performance. However, this does not give any flexibility for a user to seek conservative or aggressive behaviors from the team of robots. Furthermore, most coordination algorithms force robots to communicate at each time step, even though they may not need to. Our goal in this dissertation is to overcome these limitations by devising coordination algorithms that are parsimonious in communication, allow a user to manage the risk of the robot performance, and are resilient to worst-case robot failures and attacks. In the first part of this dissertation, we focus on designing parsimonious communication strategies for target tracking. Specifically, we investigate the problem of determining when to communicate and who to communicate with. When the robots use range sensors, the tracking performance is a function of the relative positions of the robots and the targets. We propose a self-triggered communication strategy in which a robot communicates its own position with its neighbors only when a certain set of conditions are violated. We prove that this strategy converges to the optimal robot positions for tracking a single target and in practice, reduces the number of communication messages by 30%. When tracking multiple targets, we can reduce the communication by forming subsets of robots and assigning one subset to track a target. We investigate a number of measures for tracking quality based on the observability matrix and show which ones are submodular and which ones are not. For non-submodular measures, we show a greedy algorithm gives a 1/(n+1) approximation, if we restrict the subset to n robots. In optimizing submodular functions, a common assumption is that the function value is deterministic, which may not hold in practice. For example, the sensor performance may depend on environmental conditions which are not known exactly. In the second part of the dissertation, we design an algorithm for stochastic submodular optimization. The standard formulation for stochastic optimization optimizes the expected performance. However, the expectation is a risk-neutral measure. Instead, we optimize the Conditional Value-at-Risk (CVaR), which allows the user the flexibility of choosing a risk level. We present an algorithm, based on the greedy algorithm, and prove that its performance has bounded suboptimality and improves with running time. We also present an online version of the algorithm to adapt to real-time scenarios. In the third part of this dissertation, we focus on scenarios where a set of robots may fail naturally or due to adversarial attacks. Our objective is to track as many targets as possible, a submodular measure, assuming worst-case robot failures. We present both centralized and distributed resilient tracking algorithms to cope with centralized and distributed communication settings. We prove these algorithms give a constant-factor approximation of the optimal in polynomial running time. / Doctor of Philosophy / Today, robotics and autonomous systems have been increasingly used in various areas such as manufacturing, military, agriculture, medical sciences, and environmental monitoring. However, most of these systems are fragile and vulnerable to adversarial attacks and uncertain environmental conditions. In most cases, even if a part of the system fails, the entire system performance can be significantly undermined. As robots start to coexist with humans, we need algorithms that can be trusted under real-world, not just ideal conditions. Thus, this dissertation focuses on enabling security, trustworthiness, and long-term autonomy in robotics and autonomous systems. In particular, we devise coordination algorithms that are resilient to attacks, trustworthy in the face of the uncertain conditions, and allow the long-term operation of multi-robot systems. We evaluate our algorithms through extensive simulations and proof-of-concept experiments. Generally speaking, multi-robot systems form the "physical" layer of Cyber-Physical Sytems (CPS), the Internet of Things (IoT), and Smart City. Thus, our research can find applications in the areas of connected and autonomous vehicles, intelligent transportation, communications and sensor networks, and environmental monitoring in smart cities.

Dans le domaine des systèmes temps-réel embarqués critiques, les méthodes de conception et de spécification et leurs outils associés doivent permettre le développement de systèmes au comportement temporel déterministe et, par conséquent, reproductible afin de garantir leur sûreté de fonctionnement. Pour atteindre cet objectif, on s’intéresse aux méthodologies de développement basées sur le paradigme Time-Triggered (TT). Dans ce contexte, nombre de propriétés et, en particulier, les contraintes temps-réel de-bout-en-bout, se voient satisfaites par construction. Toutefois, garantir la sûreté de fonctionnement de tels systèmes reste un défi. En général, les outils de développement existants n’assurent pas par construction le respect de l’intégralité des spécifications, celles-ci doivent, en général, être vérifiées à posteriori. Avec la complexité croissante des applications embarquées, celle de leur validation à posteriori devient, au mieux, un facteur majeur dans les coûts de développement et, au pire, tout simplement impossible. Il faut, donc, définir une méthode qui, tout en permettant le développement des systèmes corrects par constructions, structure et simplifie le processus de spécification. Les méthodologies de conception de haut niveau à base de composants, qui permettent la conception et la vérification des systèmes temps-réels critiques, présentent une solution ultime pour la structuration et la simplification du processus de spécification de tels systèmes.L’objectif de cette thèse est d'associer la méthodologie BIP (Behaviour-Interaction-Priority) qui est une approche de conception basée sur composants avec la plateforme d'exécution PharOS, qui est un système d'exploitation temps-réel déterministe orienté sûreté de fonctionnement. Le flot de conception proposé dans cette thèse est une approche transformationnelle qui permet de conserver les propriétés fonctionnelles des modèles originaux de BIP. Il est composé essentiellement de deux étapes. La première étape, paramétrée par un mapping de tâche défini par l'utilisateur, permet de transformer un modèle BIP en un modèle plus restreint qui représente une description haut niveau des implémentations basées sur des primitives de communication TT. La deuxième étape permet la génération du code pour la plateforme PharOS à partir de ce modèle restreint.Un ensemble d'outils a été développé dans cette thèse afin d'automatiser la plupart des étapes du flot de conception proposé. Ceci a permis de tester cette approche sur deux cas d'étude industriels ; un simulateur de vol et un relais de protection moyenne tension. Dans les deux applications, on vise à comparer les fonctionnalités du modèle BIP avec celles du modèle intermédiaire et du code généré. On fait varier les stratégies de mapping de tâche dans la première application, afin de tester leur impact sur le code généré. Dans la deuxième application, on étudie l'impact de la transformation sur le code généré en comparant quelques aspects de performance du code générer avec ceux d'une version de l'application qui a été développée manuellement. / In hard real-time embedded systems, design and specification methods and their associated tools must allow development of temporally deterministic systems to ensure their safety. To achieve this goal, we are specifically interested in methodologies based on the Time-Triggered (TT) paradigm. This paradigm allows preserving by construction number of properties, in particular, end-to-end real-time constraints. However, ensuring correctness and safety of such systems remains a challenging task. Existing development tools do not guarantee by construction specification respect. Thus, a-posteriori verification of the application is generally a must. With the increasing complexity of embedded applications, their a-posteriori validation becomes, at best, a major factor in the development costs and, at worst, simply impossible. It is necessary, therefore, to define a method that allows the development of correct-by-construction systems while simplifying the specification process.High-level component-based design frameworks that allow design and verification of hard real-time systems are very good candidates for structuring the specification process as well as verifying the high-level model.The goal of this thesis is to couple a high-level component-based design approach based on the BIP (Behaviour-Interaction-Priority) framework with a safety-oriented real-time execution platform implementing the TT approach (the PharOS Real-Time Operating System). To this end, we propose an automatic transformation process from BIPmodels into applications for the target platform (i.e. PharOS).The process consists in a two-step semantics-preserving transformation. The first step transforms a BIP model coupled to a user-defined task mapping into a restricted one, which lends itself well to an implementation based on TT communication primitives. The second step transforms the resulting model into the TT implementation provided by the PharOS RTOS.We provide a tool-flow that automates most of the steps of the proposed approach and illustrate its use on an industrial case study for a flight Simulator application and a medium voltage protection relay application. In both applications, we compare functionalities of both original, intermediate and final model in order to confirm the correctness of the transformation. For the first application, we study the impact of the task mapping on the generated implementation. And for the second application, we study the impact of the transformation on some performance aspects compared to a manually written version.

Today, many embedded or cyber-physical systems, e.g., in the automotive domain, comprise several control applications, sharing the same platform. It is well known that such resource sharing leads to complex temporal behaviors that degrades the quality of control, and more importantly, may even jeopardize stability in the worst case, if not properly taken into account. In this thesis, we consider embedded control or cyber-physical systems, where several control applications share the same processing unit. The focus is on the control-scheduling co-design problem, where the controller and scheduling parameters are jointly optimized. The fundamental difference between control applications and traditional embedded applications motivates the need for novel methodologies for the design and optimization of embedded control systems. This thesis is one more step towards correct design and optimization of embedded control systems. Offline and online methodologies for embedded control systems are covered in this thesis. The importance of considering both the expected control performance and stability is discussed and a control-scheduling co-design methodology is proposed to optimize control performance while guaranteeing stability. Orthogonal to this, bandwidth-efficient stabilizing control servers are proposed, which support compositionality, isolation, and resource-efficiency in design and co-design. Finally, we extend the scope of the proposed approach to non-periodic control schemes and address the challenges in sharing the platform with self-triggered controllers. In addition to offline methodologies, a novel online scheduling policy to stabilize control applications is proposed.

De nos jours, pour accroître le potentiel applicatif des machines de hautes puissances pulsées, il est nécessaire de développer des modulateurs compacts capables de délivrer des impulsions de l’ordre de plusieurs Mégawatts de durée pouvant atteindre plusieurs centaines de microsecondes. Cette amélioration requiert le développement de structures innovantes dont le but est de produire aussi bien des puissances moyennes que des puissances crêtes importantes. Les modulateurs étudiés dans ce mémoire sont basés sur l’utilisation de divers transformateurs pour la génération d’impulsions de très forte puissance. Le projet AGIR (acronyme de « Architecture pour la Génération d’Impulsions Rectangulaires de forte de puissance ») est réalisé dans le cadre d’un RAPID (Régime d’Appui Pour l’Innovation Duale) financé par la Direction Générale de l’Armement (DGA). Le projet est une collaboration avec EFFITECH, une entreprise spécialisée dans les puissances pulsées. L’objectif est de développer deux générateurs pour deux gammes de puissance crête (jusqu’à 10MW pour l’un et 1GW pour l’autre). Le premier modulateur « AGIR1 » repose sur l’association d’un convertisseur AC-DC et de 12 convertisseurs résonants DC-DC qui permettent la génération de plusieurs types d’impulsions (fort courant ou forte tension) en fonction de la configuration choisie. Le second modulateur repose sur le développement d’un transformateur impulsionnel à quatre primaires synchronisés. Chaque primaire est relié à un système de mise en forme de type Blumlein dont le déclenchement est assuré par un éclateur pressurisé à trois électrodes. La synchronisation des quatre éclateurs est assurée par un générateur impulsionnel innovant à faible gigue. La principale difficulté du travail effectué au laboratoire réside dans l’étude des différents transformateurs haute-tension utilisés (résonant ou impulsionnel) et du système de synchronisation des éclateurs. Chaque élément constituant le système est étudié et simulé de manière électrostatique, électromagnétique ou électrique avant d’être réalisé et assemblé. Des essais ponctue l’étude afin de valider le fonctionnement en récurrent avec un système de dissipation thermique adapté. / Nowadays, to increase the application potential of high power pulsed machines, it is necessary to develop compact modulators able to deliver pulses in the range of several megawatts with duration of up to several hundred microseconds. This improvement requires the development of innovative structures whose purpose is to produce both average power and large peak power. Modulators studied in this thesis are based on the use of various transformers for the generation of very high power pulses. The AGIR project (French acronym for "Architecture for Rectangular High Pulse power generation") is achieved within the framework of a RAPID (Dual Innovation Support Regime) funded by the French Defense (DGA). The project is carried on by a collaboration with EFFITECH, a company specialized in pulsed powers. The goal is to develop two generators for two peak power ranges (up to 10MW for one and 1GW for the other). The first modulator "AGIR1" is based on the association of an AC-DC converter and 12 DC-DC resonant converters allowing the generation of several types of pulses (high current or high voltage) depending on the chosen configuration. The second modulator is based on the development of a four synchronized primary pulse transformer. Each primary is connected to a Blumlein pulse forming line triggered by a three-electrode pressurized spark gap. The synchronization of the four spark gaps is ensured by an innovative pulse generator with low jitter. The main difficulty of the work which was completed in the laboratory relies in the study of the different high-voltage transformers used (resonant or pulse) and the spark gap synchronization system. Each element constituting the system is studied and simulated electrostatically, electromagnetically or electrically before being realized and assembled. Trials punctuate the study to validate the recurrent operation with a suitable heat dissipation system.

<p>Embedded computer systems are used as control systems in many products, such as VCRs, digital cameras, washing machines, automobiles, airplanes, etc. As the complexity of embedded applications grows and time-to-market of the products they are used in reduces, designing reliable systems satisfying multiple require-ments is a great challenge. Successful design, nowadays, cannot be performed without good design tools based on powerful design methodologies. These tools should explore different design alternatives to find the best one and do that at high abstraction levels to manage the complexity and reduce the design time.</p><p>A design is specified using models. Different models are used at different de-sign stages and abstraction levels. For example, the functionality of an application can be specified using hierarchical functional blocks. However, for such design tasks as mapping and scheduling, a lower-level flat model of interacting processes is needed. Deriving this model from a higher-level model of functional blocks is the main focus of this thesis. Our objective is to develop efficient strategies for such derivations, aiming at producing a process graph specification, which helps the synthesis tasks to find schedulable implementations. We proposed several strategies and evaluated them experimentally.</p>

<p>This thesis describes results from fundamental studies of liposomes intended for drug delivery and pH or temperature triggered release. In addition, the effect of lipid composition on bilayer disc formation and a potential application of the bilayer discs were investigated.</p><p>The lower pH encountered by endocytosed liposomes can be utilized to trigger drug release. The mechanisms behind cytosolic drug delivery were investigated using two different kinds of pH-sensitive liposomes. The results indicate that incorporation of non-lamellar forming lipids into the endosome membrane may allow for drug escape into the cytosol.</p><p>Temperature-sensitive liposomes containing lysolipid (LTSL) release their content almost instantly when heated to temperatures close to the gel to liquid crystalline phase transition temperature (T<i>C</i>). Morphological changes of the liposomes in response to temperature cycling were studied. Temperature cycling induced liposome openings and disintegration of the liposomes into bilayer discs. Incubation of LTSL in the presence of multilamellar liposomes (MLVs) resulted in relocalisation of lysolipid into the MLVs, which affected the rapid release from LTSL. We propose that the presence of micelle-forming components, such as lysolipids and PEG-lipids, facilitates the formation of defects and membrane openings during the initial phase of membrane melting, resulting in the observed rapid release. Similar to added lysolipids, also hydrolysis generated lysolipids induce disc-formation upon heating through T<i>C</i> of the lipid mixture.</p><p>Two fundamentally different micelles may form in PEG-lipid/lipid mixtures. We found that discoidal structures are preferred over cylindrical micelles when the mixture contains components that reduce the spontaneous curvature, increase the monolayer bending modulus, or reduce PEG-lipid/lipid miscibility. The large discoidal micelles found at low PEG-lipid content are better described as bilayer discs. We evaluated such discs as model membranes in drug partitioning studies, and suggest that they, in some cases, produce more accurate data than liposomes.</p>

Plasmon-resonant nanoparticle complexes show promising potential for light-triggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) ‒ using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein ‒ is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules non-covalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6-diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell’s endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer coated onto the AuNS surface (AuNS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotide, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and GFP gene silencing mediated by AuNS-PLL delivery vector. The light-triggered release of oligonucleotides could have broad applications in the study of cellular processes and in the development of intracellular targeted therapies.

Ethernet Switches are widely used in real-time distributed systems as a solution to guarantee the real-time behavior in communication. In this solution there are still some limitations which are the important obstacles obtaining timeliness in the network. These limitations are the limited number of priority levels as well as the possibility of memory overruns with consequent messages. The mentioned limitations can be eliminated using a master/slave technique along with FTT paradigm. The FTT-SE protocol which is a technique based on the master/slave and FTT methods was proposed to overcome the mentioned limitations. However, the FTT-SE protocol has been investigated for a small network architecture with a single switch and master node. Extension of this solution to larger networks is still an open issue. Three different architectures were suggested to scale the FTT-SE to large scale network. In this thesis we propose a solution that extends the FTT-SEprotocol while keeping the real-time behavior of the network. In this solution, we divided the network into a set of sub-networks, each contains one switch, set of slave nodes and one master node that connected to the associated switch in the network. Moreover, the switches are connected together directly without gateways and form a tree topology network. The solution includes both synchronous and asynchronous traffic in the network. We also show that the timeliness of the traffic can still be enforced. Moreover, to validate the solution we have designed and implemented a simulator based on the Matlab/Simulink which is a tool to evaluate different network architecture using Simulink blocks. All transmission can be visualized by the ordinary Scope block in the Simulink. Moreover, the end-to-end delay for all messages is calculated after the simulation running to show the response time of the network. Furthermore, the response time analysis is done for both synchronous and asynchronous messages in this thesis according to the proposed solution. The results from simulation and the analysis are compared together to validate the investigations.