La spasticité et la douleur neuropathique sont deux symptômes apparaissant fréquemment après une lésion médullaire. La spasticité est définie comme une augmentation du tonus musculaire qui provoque des contractures, tandis que la douleur neuropathique se caractérise par des sensations douloureuses survenant suite à une lésion du système nerveux.Ces deux symptômes résultent en partie d’une désinhibition des réseaux neuronaux sous-lésionnels lié à une diminution de l’expression du cotransporteur potassium-chlorure type 2 (KCC2). Pour être efficace,l’inhibition nécessite l’action de cette protéine qui extrait les ions chlorure des neurones.L’objectif de la présente thèse est donc d’identifier des médicaments capables d’activer KCC2 afin de restaurer l’inhibition dans le but de traiter la spasticité et la douleur neuropathique.Dans un premier temps, nos résultats ont montré que l’activation de récepteurs sérotoninergiques 5-HT2A avec le TCB-2 rétablit l’expression de KCC2 dans la corne dorsale après une lésion médullaire ou névrectomie. Or le TCB-2 réduit seulement la douleur neuropathique après la lésion spinale.Par la suite, nous avons identifié la prochlorperazine comme une molécule augmentant l’activité de KCC2. Si la prochlorperazine est efficace contre la spasticité, elle a néanmoins un effet plus modeste envers l’allodynie mécanique suite à une lésion médullaire.Enfin, nous avons démontré que la diminution de KCC2,ainsi que l’hyperexcitabilité des motoneurones suite à la lésion, dépendent de l’activation des calpaïnes.Cette thèse valide KCC2 comme une cible thérapeutique dans le traitement de la spasticité et la douleur neuropathique suite à une lésion médullaire. / Spasticity and neuropathic pain are two symptoms that arise frequently after a spinal cord injury. Spasticity is defined as an increase of the muscle tone contributing to cramps, whereas neuropathic pain consists of painful responses caused by a damaged nervous system. Both symptoms arise, in part, due to a loss of inhibition in the sublesional neural networks, linked to a downregulation of the expression of potassium-chloride cotransporter type 2 (KCC2). For inhibition to be efficient, the action of this protein, which extrudes chloride ions from neurons, is needed.The objective of this thesis is, therefore, to identify drugs capable of activating KCC2 to recover inhibition with the objective of treating spasticity and neuropathic pain.First, our results have proven that the activation of serotonin receptors 5-HT2A with TCB-2 restores KCC2 expression in the dorsal horn after a spinal cord or peripheral nerve injury. However, TCB-2 reduces neuropathic pain after a spinal cord injury exclusively.In the next stage of the work, we have identified prochlorperazine as an enhancer of KCC2 activity. Prochlorperazine is efficient against spasticity, although it only showed a modest reduction of mechanical hyperalgesia in animals with a spinal cord injury.Lastly, we have proven that KCC2 downregulation and motoneuron hyperexcitability after a spinal cord injury depend on the overactivation of calpains.This thesis validates KCC2 as a druggable target to treat spasticity and neuropathic pain after spinal cord injury.

In this paper SAM (self-assembled monolayers) is used to passivate cobalt microbumps for 3D-stacking of Si chips. The SAM deposition process is optimized, using input from characterization techniques such as water contact angle measurement, ATR, AFM and XPS analysis in order to form a monolayer of Thiols-SAM on cobalt microbumps. A 3D stacked Si chips test vehicle was used to demonstrate the effectiveness of the SAM coating on cobalt bumps by measuring the electrical continuity of daisy chains.

The OS (operating system) is the primary target of todays attacks. A single exploitable defect can be sufficient to break the security of the system and give fully control over all the software on the machine. Because current operating systems are too large to be defect free, the best approach to improve the system security is to reduce their code to more manageable levels. This work shows how the security-critical part of the OS, the so called TCB (Trusted Computing Base), can be reduced from millions to less than hundred thousand lines of code to achieve these security goals. Shrinking the software stack by more than an order of magnitude is an open challenge since no single technique can currently achieve this. We therefore followed a holistic approach and improved the design as well as implementation of several system layers starting with a new OS called NOVA. NOVA provides a small TCB for both newly written applications but also for legacy code running inside virtual machines. Virtualization is thereby the key technique to ensure that compatibility requirements will not increase the minimal TCB of our system. The main contribution of this work is to show how the virtual machine monitor for NOVA was implemented with significantly less lines of code without affecting the performance of its guest OS. To reduce the overall TCB of our system, other parts had to be improved as well. Additional contributions are the simplification of the OS debugging interface, the reduction of the boot stack and a new programming language called B1 that can be more easily compiled.

Trust is a concept of increasing importance in today’s information systems where information storage and generation to a higher extent is distributed among several entities throughout local or global networks. This trend in information science requires new ways to sustain the information security in the systems. This document defines trust in the context of a terminal-based system and analyzes the architecture of a distributed terminal-based system using threat modeling tools to elicit the prerequisites for trust in such a system. The result of the analysis is then converted into measures and activities that can be performed to fulfill these prerequisites. The proposed measures include hardware identification and both hardware and software attestation supported by the Trusted Computing Group standards and Trusted Platform Modules that are included in a connection handshake protocol. The proposed handshake protocol is evaluated against a practical case of a terminal-based casino system where the weaknesses of the protocol, mainly the requirement to build a system-wide Trusted Computing Base, are made evident. Proposed solutions to this problem such as minimization of the Trusted Computing Base are discussed along with the fundamental reason of the problem and the future solutions using the next generation of CPUs and Operating System kernels.

The project is aimed at testing the kernels of real-time OS within the HC08 platform. The RM, EDF and polled loop mechanisms are being compared as well as freely available FreeRSTOS and QP systems. The project also incorporates descriptions of techniques used in the development, obtaining and the implementation of test environments. The evaluation is based on the tests made within the HC08 platform and the knowledge gained from the programming for every individual type of real-time OS.

The OS (operating system) is the primary target of todays attacks. A single exploitable defect can be sufficient to break the security of the system and give fully control over all the software on the machine. Because current operating systems are too large to be defect free, the best approach to improve the system security is to reduce their code to more manageable levels. This work shows how the security-critical part of the OS, the so called TCB (Trusted Computing Base), can be reduced from millions to less than hundred thousand lines of code to achieve these security goals. Shrinking the software stack by more than an order of magnitude is an open challenge since no single technique can currently achieve this. We therefore followed a holistic approach and improved the design as well as implementation of several system layers starting with a new OS called NOVA. NOVA provides a small TCB for both newly written applications but also for legacy code running inside virtual machines. Virtualization is thereby the key technique to ensure that compatibility requirements will not increase the minimal TCB of our system. The main contribution of this work is to show how the virtual machine monitor for NOVA was implemented with significantly less lines of code without affecting the performance of its guest OS. To reduce the overall TCB of our system, other parts had to be improved as well. Additional contributions are the simplification of the OS debugging interface, the reduction of the boot stack and a new programming language called B1 that can be more easily compiled.

In this paper SAM (self-assembled monolayers) is used to passivate cobalt microbumps for 3D-stacking of Si chips. The SAM deposition process is optimized, using input from characterization techniques such as water contact angle measurement, ATR, AFM and XPS analysis in order to form a monolayer of Thiols-SAM on cobalt microbumps. A 3D stacked Si chips test vehicle was used to demonstrate the effectiveness of the SAM coating on cobalt bumps by measuring the electrical continuity of daisy chains.

The integrity of information systems is predicated on the integrity of processes that manipulate data. Processes are conventionally executed using the conventional von Neumann (VN) architecture. The VN computation model is plagued by a large trusted computing base (TCB), due to the need to include memory and input/output devices inside the TCB. This situation is becoming increasingly unjustifiable due to the steady addition of complex features such as platform virtualization, hyper-threading, etc. In this research work, we propose a new model of computation - TCB minimizing model of computation (TMMC) - which explicitly seeks to minimize the TCB, viz., hardware and software that need to be trusted to guarantee the integrity of execution of a process. More specifically, in one realization of the model, the TCB can be shrunk to include only a low complexity module; in a second realization, the TCB can be shrunk to include nothing, by executing processes in a blockchain network. The practical utilization of TMMC using a low complexity trusted module, as well as a blockchain network, is detailed in this research work. The utility of the TMMC model in guaranteeing the integrity of execution of a wide range of useful algorithms (graph algorithms, computational geometric algorithms, NP algorithms, etc.), and complex large-scale processes composed of such algorithms, are investigated.

Trust in information systems stem from two key properties of responses to queries regarding the state of the system, viz., i) authoritativeness, and ii) unbiasedness. That the response is authoritative implies that i) the provider (source) of the response, and ii) the chain of delegations through which the provider obtained the authority to respond, can be verified. The property of unbiasedness implies that no system data relevant to the query is deliberately or accidentally suppressed. The need for guaranteeing these two important properties stem from the impracticality for the verifier to exhaustively verify the correctness of every system process, and the integrity of the platform on which system processes are executed. For instance, the integrity of a process may be jeopardized by i) bugs (attacks) in computing hardware like Random Access Memory (RAM), input/output channels (I/O), and Central Processing Unit( CPU), ii) exploitable defects in an operating system, iii) logical bugs in program implementation, and iv) a wide range of other embedded malfunctions, among others. A first step in ensuing AU properties of geographic queries is the need to ensure AU responses to a specific type of geographic query, viz., point-location. The focus of this dissertation is on strategies to leverage assured point-location, for i) ensuring authoritativeness and unbiasedness (AU) of responses to a wide range of geographic queries; and ii) useful applications like Secure Queryable Dynamic Maps (SQDM) and trustworthy redistricting protocol. The specific strategies used for guaranteeing AU properties of geographic services include i) use of novel Merkle-hash tree- based data structures, and ii) blockchain networks to guarantee the integrity of the processes.