Explorations of identity in Philip K. Dick's Do androids dream of electric sheep?

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Use of cellular impedance to characterize ligand functional selectivity at G protein-coupled receptors

Les récepteurs couplés aux protéines G (RCPGs) représentent la plus grande famille de cibles thérapeutiques pour le traitement d’une panoplie de pathologies humaines. Bien que plusieurs décennies de recherche aient permis de façonner nos connaissances sur ces protéines membranaires, notre compréhension des déterminants moléculaires de leur activité signalétique reste encore limitée. De ces domaines de recherche, une avancée récente a mis à jour un nouveau phénomène, appelé sélectivité fonctionnelle des ligands, qui a bouleversé les paradigmes décrivant leu fonctionnement de ces récepteurs. Ce concept émane d’observations montrant que l’activité pharmacologique de certains ligands n’est pas nécessairement conservée sur tout le répertoire signalétiques connu du récepteur et peu se restreindre à l'activation sélective d’un sous-groupe de voies de signalisation.Ce nouveau modèle pharmacologique de l'activation des RCPG ouvre de nouvelles possibilités pour la découverte de médicaments plus efficace et sûr, ciblant les RCPGs. En effet, il permet la conception de molécules modulant spécifiquement les voies signalétiques d’intérêt thérapeutique, sans engager les autres voies qui pourraient mener à des effets secondaires indésirables ou de la tolérance. Cette thèse décrit l'utilisation d'une nouvelle approche sans marquage, basée sur la mesure du changement l'impédance cellulaire. Par la mesure des changements cellulaires, comme la morphologie, l’adhésion et/ou la redistribution des macromolécules, cette approche permet de mesurer de façon simultanée l'activité de plusieurs voies de signalisation impliqués dans ces réponses. Utilisant le récepteur β2-adrénergique (β2AR) comme modèle, nous avons démontré que les variations dans l’impédance cellulaire étaient directement liées à l’activation de multiples voies de signalisation suite à la stimulation du récepteur par son ligand. L’agoniste type du β2AR, l’isoprotérénol, s’est avéré induire une réponse d’impédance dose-dépendante constituée, dans le temps, de plusieurs caractéristiques distinctes pouvant être bloquées de façon compétitive par l’antagoniste ICI118,551 Par l’utilisation d’inhibiteurs sélectifs, nous avons été en mesure de déterminer la contribution de plusieurs voies signalétiques canoniques, comme les voies dépendantes de Gs et Gi, la production d’AMPc et l’activation de ERK1/2, sur ces changements. De plus, la dissection de la réponse d’impédance a permis d’identifier une nouvelle voie de mobilisation du Ca2+ contribuant à la réponse globale des changements initiés par la stimulation du β2AR. Dans une autre étude, nous avons rapporté que la réponse calcique induite par le β2AR serait attribuable à une transactivation Gs-dépendant du récepteur purinergique P2Y11, lui-même couplé à la protéine Gq. La mesure d’impédance permettant de distinguer et de décrire une pléiade d’activités signalétiques, nous avons émis l’hypothèse que des ligands arborant des profils signalétiques différents généreraient des réponses d’impédance distinctes. Le criblage d’une librairie de ligands spécifiques au β2AR a révélé une grande variété de signatures d’impédance. Grâce au développement d’une approche computationnelle innovatrice, nous avons été en mesure de regrouper ces signatures en cinq classes de composés, un regroupement qui s’est avéré hautement corrélé avec le profil signalétique des différents ligands. Nous avons ensuite combiné le criblage de composés par impédance avec l’utilisation d’inhibiteurs sélectifs de voies signalétiques afin d’augmenter la résolution du regroupement. En évaluant l’impact d’une voie signalétique donnée sur la signature d’impédance, nous avons été en mesure de révéler une plus grande variété de textures parmi les ligands. De plus, cette méthode s’est avérée efficace pour prédire le profil signalétique d’une librairie de composés non caractérisés, ciblant le β2AR. Ces travaux ont mené à l’élaboration d’une méthode permettant d’exprimer visuellement la sélectivité fonctionnelle de ligands et ont révélé de nouvelles classes de composés pour ce récepteur. Ces nouvelles classes de composés ont ensuite été testées sur des cardiomyocytes humains, confirmant que les composés regroupés dans différentes classes produisent des effets distincts sur la contractilité de ces cellules. Globalement, ces travaux démontrent la pertinence de l’utilisation de l’impédance cellulaire pour une évaluation précise des différences fonctionnelles parmi les composés ciblant les RCPGs. En fournissant une représentation pluridimensionnelle de la signalisation émanant des RCPGs à l’aide d’un seul essai ne requérant pas de marquage, les signatures d’impédance représentent une stratégie simple et innovante pour l’évaluation de la fonctionnalité sélective des ligands. Cette méthode pourrait être d’une grande utilité dans le processus de découverte de nouveaux médicaments.

Dielecting-resonator-loaded microstrip antenna for enhanced impedance bandwidth and efficiency

A new method for enhancing the 2.1 VSWR impedance bandwidth of microstrip antennas is presented. Bandwidth enhancement is achieved by loading the microstrip antenna by a ceramic microwave dielectric resonator (DR). The validity of this technique has been established using rectangular and circular radiating geometries. This method improves the bandwidth of a rectangular microstrip antenna to more than 10% (= 5 times that of a conventional rectangular microstrip antenna) with an enhanced gain of I dB

Multiple edges of a quantum Hall system in a strong electric

In this paper we show that if the electrons in a quantum Hall sample are subjected to a constant electric field in the plane of the material, comparable in magnitude to the background magnetic field on the system of electrons, a multiplicity of edge states localized at different regions of space is produced in the sample. The actions governing the dynamics of these edge states are obtained starting from the well-known Schrödinger field theory for a system of nonrelativistic electrons, where on top of the constant background electric and magnetic fields, the electrons are further subject to slowly varying weak electromagnetic fields. In the regions between the edges, dubbed as the "bulk," the fermions can be integrated out entirely and the dynamics expressed in terms of a local effective action involving the slowly varying electromagnetic potentials. It is further shown how the bulk action is gauge noninvariant in a particular way, and how the edge states conspire to restore the U(1) electromagnetic gauge invariance of the system. In the edge action we obtain a heretofore unnoticed gauge-invariant term that depends on the particular edge. We argue that this term may be detected experimentally as different edges respond differently to a monochromatic probe due to this term

Chaotic dynamics of electric-field domains in periodically driven superlattices

Self-sustained time-dependent current oscillations under dc voltage bias have been observed in recent experiments on n-doped semiconductor superlattices with sequential resonant tunneling. The current oscillations are caused by the motion and recycling of the domain wall separating low- and high-electric-field regions of the superlattice, as the analysis of a discrete drift model shows and experimental evidence supports. Numerical simulation shows that different nonlinear dynamical regimes of the domain wall appear when an external microwave signal is superimposed on the dc bias and its driving frequency and driving amplitude vary. On the frequency-amplitude parameter plane, there are regions of entrainment and quasiperiodicity forming Arnold tongues. Chaos is demonstrated to appear at the boundaries of the tongues and in the regions where they overlap. Coexistence of up to four electric-field domains randomly nucleated in space is detected under ac+dc driving.

High Selectivity Filter Employing Stepped Impedance Resonators, Series Capacitors and Defected Ground Structures for Ultra Wide Band Applications

The paper presents a compact planar Ultra Wide Band ¯lter employing folded stepped impedance resonators with series capacitors and dumb bell shaped defected ground structures. An interdigital quarter wavelength coupled line is used for achieving the band pass characteristics. The transmission zeros are produced by stepped impedance resonators. The ¯lter has steep roll o® rate and good attenuation in its lower and upper stop bands, contributed by the series capacitor and defected ground structures respectively.

Lead free heterogeneous multilayers with giant magneto electric coupling for microelectronics/microelectromechanical systems applications

Lead free magneto electrics with a strong sub resonant (broad frequency range) magneto electric coupling coefficient (MECC) is the goal of the day which can revolutionise the microelectronics and microelectromechanical systems (MEMS) industry. We report giant resonant MECC in lead free nanograined Barium Titanate–CoFe (Alloy)-Barium Titanate [BTO-CoFe-BTO] sandwiched thin films. The resonant MECC values obtained here are the highest values recorded in thin films/ multilayers. Sub-resonant MECC values are quite comparable to the highest MECC reported in 2-2 layered structures. MECC got enhanced by two orders at a low frequency resonance. The results show the potential of these thin films for transducer, magnetic field assisted energy harvesters, switching devices, and storage applications. Some possible device integration techniques are also discussed

Raman spectra of KTP crystal in an in situ electric field

Raman spectra of the KTP single crystal are recorded in electric fields (dc and ac) applied along the polar axis c. Spectra with the laser beam focused near the cathode end, anode end and the centre of the crystal are recorded. The cathode end of the crystal develops a spot ‘grey track’ where the laser beam is focused after a lapse of 5 h from the application of a dc electric field of 38 V/cm. The spectra recorded at the cathode end after the application of field show variations in intensity of bands. A new band appears at 177 cm21. Changes in band intensities are explained on the basis of changes in polarizability of the crystal due to the movement of K1 ions along the polar axis. K1 ions accumulate at the cathode end, where the ‘Grey track’ formation occurs. The intensity enhancement observed for almost all bands in the ac field is attributed to the improvement of crystalline quality.

A crack on the interface of piezo-electric bodies

Singularities of elastic and electric fields are investigated at the tip of a crack on the interface of two anisotropic piezo-electric media under various boundary conditions on the crack surfaces. The Griffith formulae are obtained for increments of energy functionals due to growth of the crack and the notion of the energy release matrix is introduced. Normalization conditions for bases of singular solution are proposed to adapt them to the energy, stress, and deformation fracture criteria. Connections between these bases are determined and additional properties of the deformation basis related to the notion of electric surface enthalpy are established.

On the correlation between electric polarizabilities and the ionization potential of atoms

It is found that the electric dipole polarizabilities of neutral atoms correlate very strongly with their first ionization potential within the groups of elements with the same angular momenta of the outermost electrons. As the latter values are known very accurately, this allows a very good (<30%) prediction of various atomic polarizabilities.

Investigation of Multiphase Power Converter using Integrated Coupled Inductor Regarding Electric Vehicle Application

The challenge of reducing carbon emission and achieving emission target until 2050, has become a key development strategy of energy distribution for each country. The automotive industries, as the important portion of implementing energy requirements, are making some related researches to meet energy requirements and customer requirements. For modern energy requirements, it should be clean, green and renewable. For customer requirements, it should be economic, reliable and long life time. Regarding increasing requirements on the market and enlarged customer quantity, EVs and PHEV are more and more important for automotive manufactures. Normally for EVs and PHEV there are two important key parts, which are battery package and power electronics composing of critical components. A rechargeable battery is a quite important element for achieving cost competitiveness, which is mainly used to story energy and provide continue energy to drive an electric motor. In order to recharge battery and drive the electric motor, power electronics group is an essential bridge to convert different energy types for both of them. In modern power electronics there are many different topologies such as non-isolated and isolated power converters which can be used to implement for charging battery. One of most used converter topology is multiphase interleaved power converter, pri- marily due to its prominent advantages, which is frequently employed to obtain optimal dynamic response, high effciency and compact converter size. Concerning its usage, many detailed investigations regarding topology, control strategy and devices have been done. In this thesis, the core research is to investigate some branched contents in term of issues analysis and optimization approaches of building magnetic component. This work starts with an introduction of reasons of developing EVs and PEHV and an overview of different possible topologies regarding specific application requirements. Because of less components, high reliability, high effciency and also no special safety requirement, non-isolated multiphase interleaved converter is selected as the basic research topology of founded W-charge project for investigating its advantages and potential branches on using optimized magnetic components. Following, all those proposed aspects and approaches are investigated and analyzed in details in order to verify constrains and advantages through using integrated coupled inductors. Furthermore, digital controller concept and a novel tapped-inductor topology is proposed for multiphase power converter and electric vehicle application.

Productivity growth in electric energy retail in Colombia. A bootstrapped malmquist indices approach

This paper offers a productivity growth estimate for electric energy commercialization firms in Colombia, using a non-parametric Malmquist bootstrap methodology. The estimation and methodology serve two main purposes. First, in Colombia Commercialization firms are subject to a price-cap regulation scheme, a non-common arrangement in the international experience for this part of the industry. Therefore the paper’s result suggest an estimate of the productivity factor to be used by the regulator, not only in Colombia but in other countries where commercialization is a growing part of the industry (renewable energy, for instance). Second, because of poor data collection from regulators and firms themselves, regulation based on a single estimation of productivity seems inappropriate and error-prone. The nonparametric Malmquist bootstrap estimation allows an assessment of the result in contrast to a single one estimation. This would open an opportunity for the regulator to adopt a narrower and more accurate productivity estimation or override an implausible result and impose a productivity factor in the price-cap to foster the development of the industry.