Recent advances in electrical engineering have let the realization of small size electrical systems for in-body applications. Today’s hybrid implantable systems combine radio frequency and biosensor technologies. The biosensors are intended for wireless medical monitoring of the physiological parameters such as glucose, pressure, temperature etc. Enabling wireless communication with these biosensors is vital to allow continuous monitoring of the patients over a distance via radio frequency (RF) technology. Because the implantable antennas provide communication between the implanted device and the external environment, their efficient design is vital for overall system reliability. However, antenna design for implantable RF systems is a quite challenging problem due to antenna miniaturization, biocompatibility with the body’s physiology, high losses in the tissue, impedance matching, and low-power requirements. This dissertation presents design and measurement techniques of implantable antennas for medical wireless telemetry. A robust stochastic evolutionary optimization method, particle swarm optimization (PSO), is combined with an in-house finite-element boundary-integral (FE-BI) electromagnetic simulation code to design optimum implantable antennas using topology optimization. The antenna geometric parameters are optimized by PSO, and a fitness function is computed by FE-BI simulations to evaluate the performance of each candidate solution. For validating the robustness of the algorithm, in-vitro and in-vivo measurement techniques are also introduced. To illustrate this design methodology, two implantable antennas for wireless telemetry applications are considered. First, a small-size dual medical implant communications service (MICS) (402 MHz – 405 MHz) and industrial, scientific, and medical (ISM) (2.4 GHz – 2.48 GHz) band implantable antenna for human body is designed, followed by a dual band implantable antenna operating also in MICS and ISM bands for animal studies. In order to test the designed antennas in-vitro, materials mimicking the electrical properties of human and rat skins are developed. The optimized antennas are fabricated and measured in the materials. Moreover, the second antenna is in-vivo tested to observe the effects of the live tissue on the antenna performance. Simulation and measurement results regarding antenna parameters of the designed antennas such as return loss and radiation pattern are given and discussed in detail. The development details of the tissue-mimicking materials are also presented.

Previous studies have shown an association between Pb exposure and intelligence quotient (IQ). Up until now, there is a lack of technology and methodology to assess the effects of long-term Pb exposure (such as de-myelination) in brain in-vivo. So we are developing a mouse model that will allow us to assess in vivo Pb in bone and brain structure and myelination using magnetic resonance imaging (MRI). In this project, we will discuss the feasibility of an in vivo x-ray fluorescence (XRF) system for the Pb measurement in the skeleton of whole mice. A review of literature is conducted in chapter 1. Health impacts of lead, measurement of lead, pre-existing bone Pb phantoms and mouse model selection are explained thoroughly. In chapter 2, calibration and minimum detection limits (MDLs) for the XRF measurements are documented. Calibration was performed using Plaster of Paris phantoms mimicking human bone doped with Pb concentrations ranging from 0 to 100 ppm. Detection limits for the pre-existing bone Pb phantoms were found to be 1.52 μg Pb/g plaster for 1-hour measurement. For 2 strains of Pb free mice (CD-1 and C57BL/6J), which had skull and hind facing detectors respectively, MDLs of 5.66 – 7.78 μg Pb/g and 6.69 – 8.50 μg Pb/g were determined for 3-hour measurement. This detectability of MDLs by the XRF system encourages us to proceed to measure mouse-mimicking phantoms. In order to evaluate the feasibility of a 109Cd XRF system for the Pb measurement in the skeleton of whole mice, mouse-mimicking phantoms were made and measured. The effect of variations in Pb distribution across the mouse and the applicability of the normalization in mice are discussed in chapter 3. To sum up, our system can measure Pb in whole mice in vivo at the levels of Pb in bone that are anticipated in brain de-myelination studies. Our results indicate that if multiple orientations (rotated) are measured in mice, the mean bone Pb level in whole mice will be determined accurately. / Thesis / Master of Science (MSc)

The effects of light, light "mimicking" chemicals, and protein synthesis inhibitors on the photo-induced carotenogenesis of Corynebacterium 7EIC were studied. Changes in the dosage of fluorescent light applied to dark grown cells showed a dose related carotenogenic response. Maintaining the same dosage but varying the wavelength of monochromatic light revealed that light with a wavelength of 280 to 450nm was responsible for photo-induction. It further showed a peak of photo-induction between the wavelengths of 370 and 430nm. The light "mimicking" chemicals antimycin A and p-Chloromercurybenzoate were shown to have no light "mimicking" effects. The transcriptional inhibitor of protein synthesis actinomycin D partially inhibited, and chloramphenicol a translational inhibitor, completely inhibited photo-induced carotenogenesis.

Dans le cadre d’une approche comportementale et compte tenu de la complexité des marchés financiers, cette thèse examine dans quelle mesure les réseaux orientés régissant l’interaction entre les investisseurs ainsi que leur comportement mimétique influencent leurs anticipations et la dynamique des prix. Nous proposons un marché artificiel d’actifs dans lequel des chartistes et des fondamentalistes opèrent et passent d’une stratégie d’investissement à une autre en fonction de leurs performances. Tout d’abord, nous étudions un réseau complet où l’interaction se fait de manière globale. Nous constatons que notre modèle révèle l’émergence de la volatilité excessive des prix lorsque les chartistes dominent le marché. Ensuite, nous portons notre attention sur des réseaux locaux où les agents se trouvent liés qu’à une partie des individus opérant dans le marché. Nous distinguons trois types de réseaux : le réseau régulier, le réseau petit monde et le réseau aléatoire. Puis, nous introduisons un nouveau modèle qui permet de contrôler (1) la direction du processus de « rewiring » des liens; (2) le caractère aléatoire du réseau et (3) l'asymétrie dans sa distribution des degrés en distinguant les stars des non-stars. Nous montrons que contrairement au degré du caractère aléatoire du réseau, l’asymétrie dans la distribution des degrés produit des effets opposés selon qu’il s’agit de « in-degree » ou de « out-degree ». Enfin, nous montrons comment ces analyses peuvent être utilisées pour produire des dynamiques de marché réalistes. Nous constatons que la présence d’un seuil d’imitation avec un coefficient de réaction élevé permet à notre modèle de reproduire les faits stylisés les plus importants / Within a behavioral approach and given the complexity of financial markets, the aim of this thesis is to examine the extent to which directed networks that governs the interaction among investors as well as their mimicking behavior influence their anticipations and the price dynamics. We propose an artificial asset market populated by chartists and fundamentalists who are allowed to switch from one trading strategy to the other according to their relative performances. Firstly, we study a fully connected network to test for a global interaction. We find that our benchmark model accounts for the emergence of excess volatility of asset prices when chartists dominate the market. Secondly, we restrict our focus to local interactions between investors. We generate a family of network structures that spans regular network, small world network and random network. Thirdly, we introduce a new model that allows us to control (1) the direction of the rewiring process of the links; (2) the randomness of the network; and (3) the asymmetry in its degree distribution by assuming that there are two classes of agents: stars and non-stars. We show that unlike the degree of the randomness of the network, the asymmetry in the degree distribution produces opposite effects depending on whether the network is outward or inward rewired. Finally, we address the question as to how this analysis can be used to produce realistic market dynamics. We find that the presence of a mimicking threshold with a high reaction coefficient provides a better approximation to the characteristics of the distribution of real returns and reproduces the most important stylized facts observed in financial time series

Many applications of ultrasound test phantoms require that the acoustical properties of the phantom should closely match those of soft tissue. Numerous commercial test phantoms of this type are available for use with clinical ultrasound scanners, which use frequencies up to 20 MHz. However, scanners designed for imaging small animals in preclinical studies, typically operate at much higher frequencies. No commercially available test phantoms exist for use at frequencies above 20 MHz. The aim of this work was to develop a tissue-mimicking-material (TMM) that closely matches the acoustic properties of small animal tissues at high frequencies (HF). Such a material would, therefore, be suitable for ultrasound test phantoms for application with HF ultrasound scanners (20 MHz to 50 MHz). A three-step approach was adopted to address this lack of a suitable HF-TMM. Firstly, verify the acoustic characteristics of the existing IEC agar-based TMM. Secondly, establish the acoustic properties (speed of sound and attenuation coefficient) of small animal tissue at high frequencies. Thirdly, develop a TMM which exhibits, as closely as possible, these small animal tissue acoustic characteristics. A pulse-echo substitution method was used throughout to characterise the materials and the tissue samples. The speed of sound and attenuation coefficient of an IEC agar-based TMM were measured using two different techniques. Initially, a widely used method was tried, where samples are wrapped in film and placed in degassed, deionised water for assessment. The second technique was developed and validated for use in this work. In this method, TMM samples were uncovered (without film) and were both stored and assessed in a TMM preserving fluid. The second method provided up to four times more consistent results. The acoustical properties of the individual components of the IEC agar-based TMM were then measured in order to determine whether the overall attenuation coefficient of the agar TMM was a linear sum of the attenuation coefficients of its component parts. Within experimental uncertainties, this was found to be the case. This is a key observation from which the formulation of an agar TMM, matching the acoustic properties of small animal tissue, can be facilitated. The acoustical properties (speed of sound and attenuation coefficient) of mouse brain, liver, and kidney were measured using a preclinical ultrasound scanner.

This work describes the development of an optical probe for measuring movement of tissue particles deep inside which are loaded by an ultrasound remote palpation device. The principle of the method is that ultrasound force which can be applied inside the tissue makes the tissue particles vibrate and this vibration phase-modulates the light intercepting the insoniified region which results in a modulated speckle intensity on detection outside the object. This speckle intensity modulation detected through the measured intensity autocorrelation is a measure of the vibration amplitude. Since the vibration amplitude is related to the local elastic properties of the medium, the measured modulation depth in intensity autocorrelation can be used to map the elastic property in the insonified region. In this work, first the ultrasound induced force is calculated for both plane and focused ultrasound beams, and converted to amplitude of vibration and refractive index modulation, solving the forward elastography equation. Light propagation inside an insonified object is modelled using Monte Carlo simulation and the amplitude and intensity correlations are computed. The modulation depth on the autocorrelation is estimated and shown that it is inversely correlated to the local elastic modulus and optical absorption coefficient. It is further shown that whereas the variation in modulation depth is linear with respect to absorption coefficient, the same variation with elastic property is nonlinear. These results are verified experimentally in a tissue mimicking phantom. The phantom was constructed out of poly vinyl alcohol(PVA) whose optical, mechanical and acoustic properties are independently controlled. It is also shown that for loading with focused ultrasound beam the displacement is almost along the ultrasound transducer axis and therefore the contribution from refractive index modulation alone can be ascertained by probing the insonified perpendicular to the transducer axis. This helps one to find the contribution to the modulation depth from the ultrasound-induced vibration, which can be used to compute a quantitative estimate of the elastic modulus from the modulation depth.

De nos jours, un des objectifs importants de la recherche bioinorganique moderne est le développement d'enzymes artificielles. L'étude séquentielle des acides aminés présents dans le centre actif des métalloenzymes peut présenter une voie possible de la stratégie de modélisation enzymatique. Cependant, les peptides linéaires ont leurs limites lors de la reconstitution des centres actifs des métalloenzymes : ils ne possèdent pas la structure tridimensionnelle bien définie, par conséquent leur structure est vulnérable vis-à-vis de la coordination ou de l’hydrolyse des azotes amidiques. La capacité de coordination des métaux par des peptides linéaires peut être améliorée, par exemple, en les attachant à une plateforme tripodale. Les composés tripodaux peuvent assurer une organisation structurale rigide ou moins flexible pour des chaînes latérales des acides aminés, créant ainsi des sites de coordination pré-organisés pour les métaux. Dans cette thèse, la synthèse et la caractérisation des ligands peptidiques tripodaux contenant de l'histidine et la formation des complexes en présence de cuivre(II) et de zinc(II) sont présentées. Les propriétés acido-basiques ont été étudiées par potentiométrie et différentes techniques spectroscopiques ont été utilisées pour la caractérisation structurale (UV-Vis, CD, ESR, RMN et MS). Outre que la caractérisation thermodynamique et structurale, des propriétés catalytiques des complexes en réaction enzymatiques (oxydation du catéchol, dismutation du superoxyde) ont également été étudiées. Nos résultats ont démontré que les ligands peptidiques tripodaux sont capables d'améliorer la stabilité des complexes métalliques et qu'ils peuvent fournir des structures adéquates pour mimer efficacement les fonctions catalytiques des enzymes. Grâce aux études approfondies et systématiques des propriétés acido-basiques et spectroscopiques, nous avons mis en évidence les forces motrices de la coordination des métaux et établi l'impact de la structure tripodale sur la stabilité, la structure et les propriétés catalytiques des complexes formés. Nos résultats confirment l'effet bénéfique des plateformes tripodales durant la complexation des métaux, et soulignent les possibilités qui s’offrent aux peptides tripodaux dans le domaine de la biomimétisme / One of the most important directions of modern bioinorganic research is the development of artificial enzymes. One pathway of enzyme modeling strategy is the study of amino acid sequences present in the active centers of metalloenzymes. Linear peptides, however, have their limitations in reconstituting the active centers of metalloenzymes, since they do not possess the well-defined three dimensional structure, therefore their structure is vulnerable towards amide nitrogen coordination/hydrolysis. Improvement of metal binding capabilities of linear peptides can be obtained by e.g. their functionalization with tripodal ligands. Tripodal compounds may provide a rigid, less flexible platform for the coordinating amino acid side chains, creating pre-organized metal binding sites. In my thesis, I present synthesis and characterization of histidine containing tripodal peptide ligands and their complex formation in presence of copper(II) and zinc(II). Solution equilibrium was studied with pH potentiometric measurements, and several spectroscopic methods were used for structural characterization (UV-Vis, CD, ESR, NMR and MS methods). Beside thermodynamic and structural characterization, enzyme mimicking catalytical properties of the complexes have also been investigated (catechol oxidation, superoxide dismutation). Our results demonstrated that tripodal peptide ligands are capable of enhancing the stability of metal-peptide complexes, and they may provide convenient structures to efficiently mimic the catalytic functions of enzymes. With thorough and systematical solution equilibrium and spectroscopic studies, we uncovered the driving forces of metal coordination, and established the impact of the tripodal structure in stability, structure and catalytic properties of the forming complexes. Our findings confirm the beneficial effect of tripodal scaffolds in peptide-type ligand-metal complexes, and emphasize the possibilities lying within tripodal peptides in the field of enzyme mimicking

The thesis "The use of maps to depict real estate tax coefficient" deals with maps as an alternative instrument of depicting data and information. Its objective is to demonstrate maps as a possible and appropriate tool to present information on management of municipalities. At first, the thesis is focused on creation of maps and their advantages of the depiction of information. The second part of the thesis deals with the importance of decentralization of government and the sense of municipalities. The thesis also debates income of municipalities, especially the real estate tax and its local coefficient, which is an important component of financial independence of municipalities. The thesis also examines the influence of depicting information in maps on the transparency of public finance. Finally, the use of maps is presented on two examples -- depiction of municipalities applying local real estate tax coefficient and testing the theory of yard stick competition by depicting information of neighbouring municipalities applying local real estate tax coefficient.

HIV-1 is a dangerous retrovirus which represents one of the world's leading health problems. HIV-1 infection is incurable and without proper treatment by antiretroviral therapy it leads to death within several years. Despite intensive research, no HIV vaccine is currently available. This thesis presents a new and unique approach which has not been used for vaccine development yet. The promising strategy is based on small binding proteins that can elicit broadly neutralizing HIV-1 antibodies by mimicking their epitopes. The aim of this project was to select and characterize small binding proteins that can successfully mimic the surface of viral envelope glycoproteins that is recognized by the broadly neutralizing HIV-1 antibodies PGT121 and PGT126. Proteins were selected from a highly complex combinatorial protein library derived from a new type of scaffold called Myomedin. Firstly, the extent of the protein library was narrowed down using the ribosome display. Then the direct sandwich ELISA screening was applied to select scaffold variants that interact with the target antibodies. In total over 200 variants were tested and several promising candidates were found. These Myomedin variants were purified, biochemically and biophysically characterised and the best ones were used to immunize mice....

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