No description available.

Fabry Disease is an X-­‐linked lysosomal storage disorder characterized by a variety of symptoms including hypohydrosis, seizures, cardiac abnormalities, skin lesions, and chronic pain. These symptoms stem from a lack of functional endogenous α-­‐ Galactosidase A (α-­GAL), which leads to an accrual of its natural substrate. The severity of the disease symptoms can be directly correlated with the amount of residual enzyme activity. It has been shown that an imino sugar, 1-deoxygalactonojirimycin (DGJ), can increase enzymatic activity and clear excess substrate. This pH-­‐dependent chaperoning phenomenon is believed to arise from the presence of aspartic acid 170 in the active site. This key residue may become protonated at lower pH, preventing a buried salt bridge from being formed. We mutated this residue to an alanine, abolishing activity, and making traditional assays impractical. We have measured the KD of chaperone for this modified active site through crystallography. Previous crystallographic studies on this enzyme have also shown a preliminary second binding site on the surface of α-­Galactosidase that prefers the β-­Galactose anomer. When β-­Galactose binds it buries a greater surface area than when α‐Galactose binds to the active site. Binding of this site by a small molecule should stabilize the native state of the enzyme, but would be sterically occluded from inhibiting active site. We have probed this second site by soaking crystals of α‐Galactosidase with a small library of compounds.

No description available.

<p>The fiber-to-the-x (FTTX) has been widely investigated as a leading access technology to meet the ever growing demand for bandwidth in the last mile. The passive optical network (PON) provides a cost-effective and durable solution. In this thesis, we investigate different aspects of the PON, in the search for cost-effective and high-performance designs of link system and devices.</p> <p>In Chapter 2, we propose a novel upstream link scheme for optical orthogonal frequency division multiplexing (OOFDM)-PON. The colorless laser diodes are used at the optical network units (ONUs), and the overlapped channel spectrum of orthogonal subcarrier multiplexing provides high spectral efficiency. At the optical line terminal (OLT), optical switch and all optical fast Fourier transform (OFFT) are adopted for high speed demultiplexing. The deterioration caused by the laser perturbation is also investigated.</p> <p>In Chapter 3, we design a novel polarization beam splitter (PBS), which is one of the most important components in polarization-controlled optical systems, e.g. the next-generation PON utilizing polarization multiplexing. Our PBS is built on a slab waveguide platform where the light is vertically confined. Planar lenses are formed to collimate and refocus light beam by converting the phase front of the beam. A planar subwavelength grating of a wedge shape induces the form birefringence, where the transverse electric (TE) and transverse magnetic (TM) waves have different effective refractive indices, and are steered to distinct directions. This design provides low insertion loss (< 0.9 dB) and low crosstalk (< -30 dB) for a bandwidth of 100 nm in a compact size, and can be realized by different material systems for easy fabrication and/or monolithic integration with other optical components.</p> <p>In Chapter 4, we study the mode partition noise (MPN) characteristics of the Fabry-Perot (FP) laser diode using the time-domain simulation of noise-driven multi-mode laser rate equation. FP laser is cheaper than the widely used distributed feedback (DFB) laser diode in PON, but its MPN is the major limiting factor in an optical transmission system. We calculate the probability density functions for each longitudinal mode. We also investigate the k-factor, which is a simple yet important measure of MPN. The sources of the k-factor are studied with simulation, including the intrinsic source of the laser Langevin noise, and the extrinsic source of the bit pattern.</p> / Doctor of Philosophy (PhD)

Ultra-thin solar cells that incorporate earth-abundant and non-toxic materials are promising candidates in the endeavor toward sustainable energy harvesting. Methods to counteract the inevitable low absorption of thinner semiconductor layers are of high interest and have raised considerable attention in the research society. In an attempt to increase the absorption of these types of assemblies, optical coupling effects between the localized surface plasmon resonances (LSPR) of disordered Au nanostructures and a Fabry-Pérot cavity were studied using a previously established absorber/spacer/reflector stack. The disordered Au array was fabricated by evaporating a thin Au film on a substrate with a 55 nm SiO2 dielectric spacer and a 100 nm Al reflecting film, followed by thermal annealing. Nominal Au film thicknesses in the range of 5-25 Å and annealing temperatures of 200-500 oC were investigated. In situ spectroscopic ellipsometry measurements during the subsequent atomic layer deposition (ALD) of tin monosulfide (SnS) allowed analysis of how the optical properties of the SnS/Au absorber layer changed as a function of the growing SnS layer thickness. By employing the Transfer Matrix Method with the estimated optical properties from the in situ analysis, the absorptance of the absorber/spacer/reflector stacks was simulated as a function of the spacer thickness, revealing any signs of the characteristic anti-crossing behavior. It was discovered that a nominal Au film thickness of 25 Å, annealed at 450 oC, and coated with a SnS film of ∼13 nm primed toward the π-phase, resulted in strong optical coupling between the cavity mode and the LSPR. The energy difference at the avoided crossing in the specular reflectance measurement gave an estimated Rabi-splitting energy of 537 meV. This corresponded to about 40% of the original LSPR energy, placing itself within the ultra-strong coupling regime. To evaluate the relevance of the thin-layered structure in photovoltaic applications, more advanced computational methods are required to estimate the useful absorption that occurs in the SnS layer. Nevertheless, these results elucidate the realization of strong optical coupling effects between disordered Au nanostructures and a Fabry-Pérot cavity, and further the possibility of using scalable fabrication methods for this type of ultra-thin absorber/spacer/reflector stack.

Cette thèse s'inscrit dans le contexte de la forte évolution du réseau d'abonnées sur fibre optique (FTTH). Elle a l'objectif d'étudier les solutions d'émetteurs dits "achromatiques" à base de nouveaux composants optoélectroniques pour les réseaux d'accès optiques multiplexés en longueurs d'onde (WDM-PON). Ces émetteurs doivent être peu chers et identiques chez tout abonné quelque soit la longueur d'onde de fonctionnement. Deux types d'émetteurs achromatiques à base de modulateur réflectif sont étudiés dans cette thèse : le laser Fabry-Perot verrouillé par injection optique (IL-FP) et le modulateur électro-absorbant amplifié en réflexion (R-EAM-SOA). Les caractéristiques de l'IL-FP en régime de verrouillage sont évaluées en termes de bruit d'intensité, de modulation, de facteur de couplage phase-amplitude,... La caractérisation tant statique que dynamique est aussi effectuée pour le second composant R-EAM-SOA. D'autres fonctionnalités de ce composant comme la détection directe et la régénération promettent son grand potentiel pour la réalisation d'un dispositif multifonctionnel pour le réseau d'accès. Il est également proposé d'utiliser pour la première fois, le laser à bâtonnets quantiques à blocage de modes (QD-MLL) comme source d'injection multi-longueurs d'onde cohérentes pour l'accès optique WDM. Il est montré qu'il est possible de supprimer le bruit de partition de modes associé à ces structures à blocage de modes. Finalement l'intégration de ces trois composants dans des architectures WDM-PON est réalisée. La faisabilité des systèmes WDM-PON à 2,5 Gb/s à base des IL-FP injectés par une source QD-MLL est évaluée pour différentes configurations et architectures réseau. La montée en débit à 10 Gb/s est prouvée en utilisant le R-EAM-SOA. Un système WDM-PON bidirectionnel avec une capacité de 240 (24 x 10) Gb/s en voie descendante et 60 (24 x 2,5) Gb/s en voie montante a été démontré en utilisant ces solutions d'émetteurs achromatiques proposées. Une des principales sources de dégradation du système WDM-PON bidirectionnel est la rétrodiffusion de Rayleigh pour laquelle le bruit interférométrique produit est étudié. L'impact de ce bruit sur les performances en transmission du système WDM-PON est aussi analysé.

Made available in DSpace on 2016-12-12T20:27:37Z (GMT). No. of bitstreams: 1 Yujuan Wang.pdf: 1608760 bytes, checksum: 9cb82304a2c95c2b0e357dc7f8449815 (MD5) Previous issue date: 2012-12-17 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This work presents the development of an FPGA-based optical interrogation system of multiplexed FBG sensors. The Fabry-Perot filter is used to implement the tunable filter method, as a demodulator for FBG sensors. The tuning signal generation for Fabry-Perot filter and the data aquisition are implemented and syncronized em FPGA. Peak-detection algorithms, based on centroid and FIR filter, are implemented em FPGA. The peak displacement detected of FBG reflected spectrum is used to refer sensed elements, such as variation of temperature and refractive index. Besides, other auxiliary digital circuits are implemented for the system configuration, visulization of the detected peak information and the serial communication to monitor entire spectra in computer. All these digital circuits are working on their own duty at the same time, synchronised by the crystal clock of FPGA. The system was used to monitor the fabrication process of an refractive index sensor. The fabricated sensor was tested by measuring the refractive index of water and sucrose. In another experiment, the system was tested by measuring the temperature of a water sample. In addition, a method to calibrate the tuning signal generator is proposed, which can also be employed in other applications that uses DA converters. Finally, the developed system was packaged to facilitate its transportation. / Este trabalho descreve a implementação de um sistema de interrogação óptico para FBGs multiplexadas, com o controle dos processos implementado em FPGA. A interrogação das FBGs é realizada por meio do método de filtro sintonizável, com o uso de filtro Fabry-Perot. Um FPGA é utilizado para gerar sinal de sintonia para o filtro Fabry-Perot e realizar a leitura do sinal espectral refletido pelas FBGs. Algoritmos de detecção de pico (centroide e filtro FIR) foram implementados no FPGA para processar os sinais refletidos por cada FBG, com o objetivo de inferir as propriedades sensoreadas, como variação de temperatura ou índice de refração. Além destes circuitos digitais, são implementados outros circuitos digitais para a configuração do sistema, para a visualização do pico detectado do sinal espectral e para o monitoramento do espectro inteiro via comunicação serial. Todos circuitos cumprem a própria função paralelamente em virtude do paralelismo do FPGA, sincronizado pelo clock do oscilador cristal do FPGA. O sistema desenvolvido foi utilizado no monitoramento do processo de fabricação de sensor de índice de refração e então na leitura do índice de refração de amostras de sacarose e água. O sistema também foi utilizado para a leitura da temperatura de amostras de água, onde foi estimada a sensibilidade e a resolução do sistema. Também foi proposto um método para a calibração do sistema, que pode ser utilizado também em outros trabalhos. O sistema final foi colocado em uma maleta para facilitar o seu transporte para o local de uso.

This thesis presents the work done on electronic transport in various interacting and non-interacting systems in one and two dimensions. The systems under study are: an interacting quantum dot [1], a non-interacting quantum wire and a ring in which time-dependent potentials are applied [2], an interacting quantum wire and networks of multiple quantum wires with resistive regions [3, 4], one-dimensional edge stages of a two-dimensional topological insulator [5], and a hybrid system of two-dimensional surface states of a three-dimensional topological insulator and a superconductor [6]. In the first chapter, we introduce a number of concepts which are used in the rest of the thesis, such as scattering theory, Landauer conductance formula, quantum wires, bosonization, topological insulators and superconductor. In the second chapter, we study transport through a quantum dot with interacting electrons which is connected to two reservoirs. The quantum dot is modeled by two sites within a tight-binding model with spinless electrons. Using the Lippman-Schwinger method, we write down an exact two-particle wave function for the dot-reservoir system with the interaction localized in the region of the dot. We discuss the phenomena of two-particle resonance and rectification. In the third chapter, we study pumping in two kinds of one-dimensional systems: (i) an infinite line connected to reservoirs at the two ends, and (ii) an isolated ring. The infinite line is modeled by the Dirac equation with two time-independent point-like backscatterers that create a resonant barrier. We demonstrate that even if the reservoirs are at the same chemical potential, a net current can be driven through the channel by the application of one or more time-dependent point-like potentials. When the left-right symmetry is broken, a net current can be pumped from one reservoir to the other by applying a time-varying potential at only one site. For a finite ring, we model the system by a tight-binding model. The ring is isolated in the sense that it is not connected to any reservoir or environment. The system is driven by one or more time-varying on-site potentials. We develop an exact method to calculate the current averaged over an infinite amount of time by converting it to the calculation of the current carried by certain states averaged over just one time period. Using this method, we demonstrate that an oscillating potential at only one site cannot pump charge, and oscillating potentials at two or more sites are necessary to pump charge. Further we study the dependence of the pumped current on the phases and the amplitudes of the oscillating potentials at two sites. In the fourth chapter, we study the effect of resistances present in an extended region in a one-dimensional quantum wire described by a Tomonaga-Luttinger liquid model. We combine the concept of a Rayleigh dissipation function with the technique of bosonization to model the dissipative region. In the DC limit, we find that the resistance of the dissipative patch adds in series to the contact resistance. Using a current splitting matrix M to describe junctions, we study in detail the conductances of: a three-wire junction with resistances and a parallel combination of resistances. The conductance and power dissipated in these networks depend in general on the resistances and the current splitting matrices that make up the network. We also show that the idea of a Rayleigh dissipation function can be extended to couple two wires; this gives rise to a finite transconductance analogous to the Coulomb drag. In the fifth chapter, we study the effect of a Zeeman field coupled to the edge states of a two-dimensional topological insulator. These edge states form two one-dimensional channels with spin-momentum locking which are protected by time-reversal symmetry. We study what happens when time-reversal symmetry is broken by a magnetic field which is Zeeman-coupled to the edge states. We show that a magnetic field over a finite region leads to Fabry-P´erot type resonances and the conductance can be controlled by changing the direction of the magnetic field. We also study the effect of a static impurity in the patch that can backscatter electrons in the presence of a magnetic field. In the sixth chapter, we use the Blonder-Tinkham-Klapwijk formalism to study trans-port across a line junction lying between two orthogonal topological insulator surfaces and a superconductor (which can have either s-wave or p-wave pairing). The charge and spin conductances across such a junction and their behaviors as a function of the bias voltage applied across the junction and various junction parameters are studied. Our study reveals that in addition to the zero conductance bias peak, there is a non-zero spin conductance for some particular spin states of the triplet Cooper pairs. We also find an unusual satellite peak (in addition to the usual zero bias peak) in the spin conductance for a p-wave symmetry of the superconductor order parameter.

La focalisation du champ électromagnétique dans les zones de champ proche et lointain est un sujet de forte actualité pour l'imagerie médicale et la radiométrie des microondes jusqu'aux ondes millimétriques. Dans ce cadre, la théorie des ondes de fuite est un formalisme élégant qui permet de décrire d'une même façon les problèmes radiatifs en champ proche et en champ lointain des microondes aux fréquences optiques. Dans cette thèse, on utilise la polyvalence de la théorie des ondes de fuite pour développer des systèmes rayonnants complexes afin de contrôler les caractéristiques radiatives en champ lointain aux fréquences submillimétriques et pour focaliser la radiation électromagnétique en champ proche aux fréquences millimétriques. Ainsi, l'utilisation de matériaux uniques comme le graphène et les cristaux liquides ont été considérés pour la conception des antennes à ondes de fuite, en obtenant des résultats très intéressants en termes de reconfigurabilité, d'efficience et de directivité. Dans ce contexte, une analyse théorique originale a fourni de nouvelles formules pour l'évaluation des caractéristiques radiatives (c.à.d. la largeur de faisceau, le niveau des lobes secondaires, etc.) des antennes à ondes de fuite. En effet, la largeur du faisceau de ces antennes est, jusqu'à présent, estimée au moyen des formules proposées pour la première fois dans les années '60 par Prof. Arthur A. OLINER. Ces formules ne tiennent en compte ni de la longueur de l'antenne (sauf pour des cas très particuliers), ni du rayonnement longitudinal, elles ne permettent donc pas une évaluation rigoureuse.En complément à la reconfigurabilité en champ lointain, les ondes de fuite offrent aussi la possibilité de focaliser la radiation en champ proche. Dans ce cas, on voit que les ondes de fuite peuvent être utilisées d'une façon efficace pour générer des faisceaux non diffractifs de Bessel à travers des systèmes rayonnants à bande étroite aux ondes millimétriques. De plus, le caractère non diffractif des faisceaux de Bessel peut aussi être utilisé pour générer des impulsions très localisées (comme les solitons en optiques) à travers la superposition continue des faisceaux de Bessel sur une large bande de fréquence. Dans ce cadre, une nouvelle formulation a été développée afin de comprendre les limitations physiques et technologiques concernant la génération des impulsions non diffractives et non dispersives, c.à.d. les X-waves. Les résultats ont montré qu'un type de systèmes rayonnants à large bande, notamment les antennes RLSA (en anglais « Radial Line Slot Array »), semblent très favorables pour la génération des X-waves. / In recent years, microwave, millimeter-wave, and THz applications such as medical and security imaging, wireless power transfer, and near-field focusing, just to mention but a few, have gained much attention in the area of ICT due to their potentially high social impact. On one hand, the need of highly-directive THz sensors with tunable radiating features in the far-field region has recently boosted the research activity in the design of flexible, low-cost and low-profile devices. On the other hand, it is of paramount importance to focus energy in the near-field region, and thus the generation of limited-diffraction waves in the microwave and millimeter-wave regime is a topic of recent increasing interest. In this context, leaky-wave theory is an elegant and extremely useful formalism which allows for describing in a common fashion guiding and radiating phenomena in both the near field and the far field, spanning frequencies from microwaves to optics passing through THz. In this PhD thesis we aim to exploit the intrinsic versatility of the leakywave approach to design advanced radiating systems for controlling the far-field radiating features at THz frequencies and for focusing electromagnetic radiation in the near field at millimeter waves. Specifically, the use of relatively new materials such as graphene and liquid crystals has been considered for the design of leaky-wave based radiators, achieving very promising results in terms of reconfigurability, efficiency, and radiating capabilities. In this context, an original theoretical analysis has provided new general formulas for the evaluation of the radiating features (e.g., half-power beamwidth, sidelobe level, etc.) of leaky-wave antennas. Indeed, the current formulations are based on several simplifying hypotheses which do not allow for an accurate evaluation of the beamwidth in different situations. In addition to the intriguing reconfigurable capabilities offered by leaky waves in far-field applications, interesting focusing capabilities can be obtained in the near field. In particular, it is shown that leaky waves can profitably be used to generate limited-diffraction Bessel beams by means of narrow-band radiators in the microwave range. Also, the use of higherorder leaky-wave modes allows for achieving almost the same performance in the millimeter-wave range, where previous designs were subjected to severe fabrication issues. Even more interestingly, the limited-diffractive character of Bessel beams can also be used to generate limited-diffraction pulses as superpositions of monochromatic Bessel beams over a considerable fractional bandwidth. In this context, a novel theoretical framework has been developed to understand the practical limitations to efficiently generate limited-diffraction, limited-dispersion pulses, such as X-waves, in the microwave/millimeter-wave range. As a result of this investigation, a class of wideband radiators has been thoroughly analyzed, showing promising capabilities for the generation of both zeroth-order and higher-order Xwaves. The latter may pave the way for the first localized transmission of orbital angular momentum in the microwave range.

Glycosphingolipid (GSL) metabolism is a complex process involving proteins and enzymes at distinct locations within the cell. Mammalian GSLs are typically based on glucose or galactose, forming glucosylceramide (GlcCer) and galactosylceramide (GalCer). Most GSLs are derived from GlcCer, which is synthesized on the cytosolic leaflet of the Golgi, while all subsequent GSLs are synthesized on the lumenal side. We have utilized both pharamacological and genetic manipulation approaches to selectively regulate GSL metabolism and better understand its mechanistic details. We have developed analogues of GlcCer and GalCer by substituting the fatty acid moiety with an adamanatane frame. The resulting adamantylGSLs are more water-soluble than their natural counterparts. These analogues selectively interfere with GSL metabolism at particular points within the metabolic pathway. At 40 µM, adaGlcCer prevents synthesis of all GSLs downstream of GlcCer, while also elevating GlcCer levels, by inhibiting lactosylceramide (LacCer) synthase and glucocerebrosidase, respectively. AdaGalCer specifically reduces synthesis of globotriaosylceramide (Gb3) and downstream globo-series GSLs. AdaGalCer also increases Gaucher disease N370S glucocerebrosidase expression, lysosomal localization and activity. AdaGSLs, therefore, have potential as novel therapeutic agents in diseases characterized by GSL anomalies and as tools to study the effects of GSL modulation. Two predominant theories have been developed to explain how GlcCer accesses the Golgi lumen: one involving direct translocation from the cytosolic-to-lumenal leaflet of the Golgi by the ABC transporter P-glycoprotein (P-gp, ABCB1, MDR1), and the other involving retrograde transport of GlcCer by FAPP2 to the ER, followed by entry into the vesicular transport system for Golgi lumenal access. To examine the in vivo involvement of P-gp in GSL metabolism, we generated a knockout model by crossbreeding the Fabry disease mouse with the P-gp knockout mouse. HPLC analyses of tissue Gb3 levels revealed a tissue-specific reduction in MDR1/Fabry mice. TLC analyses, however, did not show such reduction. In addition, we performed a gene knockdown study using siRNA against P-gp and FAPP2. Results show these siRNA to have distinct effects on GSL levels that are cell-type specific. These results give rise to the prospect of unique therapeutic approaches by targeting P-gp or FAPP2 for synthesis inhibition of particular GSL pathways.