"This dissertation describes the development of a methodology for implementing robotic systems for interventional procedures under intraoperative Magnetic Resonance Imaging (MRI) guidance. MRI is an ideal imaging modality for surgical guidance of diagnostic and therapeutic procedures, thanks to its ability to perform high resolution, real-time, and high soft tissue contrast imaging without ionizing radiation. However, the strong magnetic field and sensitivity to radio frequency signals, as well as tightly confined scanner bore render great challenges to developing robotic systems within MRI environment. Discussed are potential solutions to address engineering topics related to development of MRI-compatible electro-mechanical systems and modeling of steerable needle interventions. A robotic framework is developed based on a modular design approach, supporting varying MRI-guided interventional procedures, with stereotactic neurosurgery and prostate cancer therapy as two driving exemplary applications. A piezoelectrically actuated electro-mechanical system is designed to provide precise needle placement in the bore of the scanner under interactive MRI-guidance, while overcoming the challenges inherent to MRI-guided procedures. This work presents the development of the robotic system in the aspects of requirements definition, clinical work flow development, mechanism optimization, control system design and experimental evaluation. A steerable needle is beneficial for interventional procedures with its capability to produce curved path, avoiding anatomical obstacles or compensating for needle placement errors. Two kinds of steerable needles are discussed, i.e. asymmetric-tip needle and concentric-tube cannula. A novel Gaussian-based ContinUous Rotation and Variable-curvature (CURV) model is proposed to steer asymmetric-tip needle, which enables variable curvature of the needle trajectory with independent control of needle rotation and insertion. While concentric-tube cannula is suitable for clinical applications where a curved trajectory is needed without relying on tissue interaction force. This dissertation addresses fundamental challenges in developing and deploying MRI-compatible robotic systems, and enables the technologies for MRI-guided needle-based interventions. This study applied and evaluated these techniques to a system for prostate biopsy that is currently in clinical trials, developed a neurosurgery robot prototype for interstitial thermal therapy of brain cancer under MRI guidance, and demonstrated needle steering using both asymmetric tip and pre-bent concentric-tube cannula approaches on a testbed."

The concept of introducing engineering principles of abstraction and standardization into synthetic biology has received increasing attention in the past several years and continues to be in the forefront of synthetic biology. One direction being pursued by synthetic biologists is creation of modular biological parts (BioBrickTM) that can be readily synthesized and mixed together in different combinations. However, most standard BioBrickTM parts in the Registry were designed for E. coli, although synthesis of specific BioBrickTM parts for other bacteria, such as for yeast and cyanobacteria, have begun. Besides, at the present time, there are only three chassis, which include E. coli, Bacillus subtilis, and a cell-free chassis, available in the Registry. Thus, the choices of BioBrickTM chassis are very limited. In addition, most BioBrickTM parts in the Registry have not been characterized. In the present study, the BioBrickTM concept was extended to the photosynthetic bacteria, Rhodobacter sphaeroides. In order to do that, a BioBrickTM compatible gene expression system was designed to convert R. sphaeroides to potential solar powered bio-factories or bio-refineries. This gene expression system was composed of BioBrickTM promoters, Ribosome Binding Sites (RBSs), and terminators in a BioBrickTM compatible cloning vector and its function has been validated through the expression of fluorescent proteins. In addition, a bioluminescence-based BioBrickTM characterization method was developed in this study. This method was based on a cloning vector that includes two adjacent operons, with each expressing a different luciferase reporter gene. The measured optical signals from the two expressed bioluminescent reporters were then used to predict the performance of promoters, RBSs, and terminators. Based on this bioluminescence-based BioBrickTM characterization method, two BioBrickTM characterizations kits, one for E. coli and one for R. sphaeroides, were developed. BioBrickTM parts that include seven promoters, six RBSs, and six terminators were characterized using the E. coli characterization kit. R. sphaeroides BioBrickTM parts were characterized when R. sphaeroides containing the BioBrickTM measurement constructs were cultured by both anaerobic photosynthesis and by aerobic respiration respectively. The experimental results showed that the activities of these R. sphaeroides BioBrickTM parts were very similar for the cells growing under two different conditions.

A prop profile of a differential geometric structure is a minimal resolution of an algebraic prop such that representations of this resolution are in one-to-one correspondence with structures of the given type. We begin this thesis with a detailed account of the algebraic tools necessary to construct prop profiles; we treat operads and props, and resolutions of these through Koszul duality. Our main results can be summarized as follows. Firstly, we contribute to the work of S.A. Merkulov on the prop profiles of Poisson and Nijenhuis structures. We prove that the operad of the latter prop profile is Koszul by showing that it has a PBW-basis, and we provide a geometrical interpretation of the former in terms of an L-infinity structure on the structure sheaf of a manifold. Secondly, we construct prop profiles of compatible Poisson and Nijenhuis structures. Representations of minimal resolutions of props correspond to Maurer-Cartan elements of certain Lie algebras associated to the resolved props. Also the differential geometric structures are defined as solutions of Maurer-Cartan equations. We show the correspondence between props and differential geometry by providing explicit isomorphisms between these Lie algebras. Thirdly, in order to construct the prop profiles of compatible Poisson and Nijenhuis structures we study operads of compatible algebraic structures. By studying Cohen-Macaulay properties of posets associated to such operads we prove the Koszulness of a large class of operads of compatible structures.

L'utilisation de l'amidon comme agent de remplissage, agent liant ou agent désagrégeant est très répandue dans l'industrie pharmaceutique. Des modifications chimiques effectuées sur ce polymère auront une influence sur ses propriétés rhéologiques. La carboxyméthylation de l'amidon génère un excipient dont les propriétés de gastro-protection ainsi que de libération contrôlée pour plusieurs catégories de principes bioactifs ont été démontrées lors de différentes études (Calinescu et al., 2005; 2007; Massicotte et al., 2008). Le concept d'immunisation mucosale lors de la vaccination est basé sur le fait que plusieurs pathogènes ont comme porte d'entrée dans l'organisme les muqueuses (par exemple celles du tractus respiratoire ou gastro-intestinal). Dans cette optique, pour contrer ou prévenir une infection, il faut cibler l'induction de l'immunité mucosale au site d'entrée du pathogène afin d'obtenir une protection optimale. Les protéines végétales incluant des fragments immunogènes spécifiques d'agents infectieux peuvent être utilisées à des fins d'immunisation orale pour une stimulation de l'appareil lymphoïde de la muqueuse intestinale. Une limite à cette approche est la barrière stomacale par rapport au pH gastrique et à l'activité protéolytique pouvant dégrader le matériel immunogène d'intérêt. Il était important de protéger les protéines immunogènes en incorporant les extraits végétaux dans une matrice polymérique utilisée à des fins de transport jusqu'à la muqueuse intestinale. Pour ce faire, les extraits végétaux lyophilisés ont été formulées avec le carboxyméthyl amidon (CMA) offrant une protection gastrique et une libération ciblée de l'actif au niveau intestinal. Lors de la libération des extraits végétaux dans la solution simulant les conditions intestinales (SIF), une destruction des protéines à été observée. L'utilisation d'inhibiteurs de protéases a été testée d'une part dans le milieu de libération et d'autre part dans la formulation elle-même. La libération des agents bioactifs non dégradés a été observée avec l'utilisation du Pefabloc SC à une concentration de 1,6 % (w/w) dans la formulation. A cette concentration, une stabilisation des protéines dans le SIF est observée pendant 6 h. L'utilisation de la lipase comme marqueur enzymatique à permis de donner une information sur la conservation de la structure protéique des éléments bioactifs lors de leur libération. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Vaccination, Plantes transgéniques, Polymères biocompatibles, Amidon, Voie orale, Gastro protection, Libération contrôlée, Inhibiteur de protéases.

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A novel hierarchical flexing and stretching strategy for rigid semiconducting substrates was devised. Architectures for comprehensively compliant semiconductors were created as a result. Si and GaN-on-Si have been segmented into both highly flexible and rigid segments. An advanced controlled cleavage technique has been integrated into the manufacturing process. The bending radius of the substrate has been decoupled from the substrate thickness thus allowing for higher mechanical stability, while achieving bending radii below 250 .m. Novel fabrication workflows have been created, one of which is completely compatible with CMOS fabrication techniques, while still being cost effective. Each of the rigid segments have been designed to carry in excess of its own weight. The reliability of the interconnecting springs was examined by rugged cyclic bending and twisting tests. Finite element simulations in COMSOL exhibited no stress for the rigid segments. For the first time a flexible and/or stretchable Si substrate has been integrated with pick and place tool technology. Additionally the platform serves as a More-than-Moore technology, by folding the monocrystalline substrate on top of itself, while routing power through the flexible segments. This More-than-Moore (MtM) technology has the advantages of System-in-Package (SiP) but does not have the additional costs. From this compliant approach a qubic 4D electronic platform was created. An aerially deployable electronic system was achieved by incorporating thermal paste into the qubic platform. Energy storage, sensing, and actuating were successfully tested on the system. Buried cavities for microfluidics were developed for on-chip chemical and biological processes. A platform was developed for µTF-SOFCs deposition. Cavities were interconnected subterraneously and columnar anodes were developed to enhance the fuel flow in the fuel cell electrode. The triple phase boundary (TPB) was enhanced by over an order of magnitude in comparison to standard processing techniques. A subsequent, microfluidic platform was developed for biological applications. The wettability of the platform gave good results for water, as well as for neurobasal media buffer. Tests indicate that neurons can grow directly on the platform.

This study focuses on creating a spectral matching algorithm that modifies the real strong ground motions in the time domain by adding wavelets adjustment to the acceleration time series. The spectral matching procedure is at its core a nonlinear problem, thus a nonlinear solving method was employed in the proposed algorithm. The Broyden updating method was selected as the nonlinear solving method because it does not require a differentiation analysis. The Broyden updating also makes use the information of spectral misfit and wavelet magnitudes vector to approximate the Jacobian matrix which expected to give an efficient calculation. A parametric study was numerically conducted to obtain a set of gain factors that reduce the computational time and minimize the spectra misfit. The study was conducted using ten different ground motions, taken from FEMA P-695 (FEMA, 2009), which represent far field, near field-pulse and near field-no pulse earthquake ground motions. A study of compatible wavelet functions was carried out to determine the appropriate wavelet function for the proposed method. The study include the baseline drift, the frequency and time resolution, and the cross correlation between wavelet adjustments during the spectra matching procedure. Based on this study, the corrected tapered cosine wavelet was selected to be used in the proposed algorithm. The proposed algorithm has been tested and compared with other methods that are commonly used in spectral matching; the RSPMatch method and the frequency domain method. The comparing parameters were the computational time, the average misfit, the maximum misfit and error, the PGA, PGV, PGD, the Arias Intensity and the frequency content for both acceleration and displacement time histories. The result showed that the proposed method is able to match the target while preserving the energy development and the frequency content of the original time histories. / Master of Science

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