Dissertations / Theses on the topic 'Protons Lithium'

L'implantation de protons a des energies de l'ordre du mev, permet de realiser des guides optiques dans le niobate de lithium (linbo#3). Les effets d'endommagement nucleaire du reseau cristallin induits par l'implantation de protons dans linbo#3 ont ete etudies en fonction de plusieurs parametres d'implantation (energie, dose, et duree de recuit post-implantation) par la spectroscopie de retrodiffusion de rutherford en geometrie de canalisation (rbs-c). Une analyse de la section efficace de decanalisation en fonction de l'energie des ions he#+ d'analyse a permis de determiner la nature physique des defauts majoritairement presents dans le reseau. Dans le contexte du modele de quere, il a ete montre que les defauts induits sont de type ponctuel, ce qui a ete confirme par des observations de microscopie electronique. La caracterisation optique des defauts par spectroscopie d'absorption dans le visible, et par transformee de fourrier inverse dans l'infrarouge, a permis de discuter les effets chimiques de l'implantation, lies a la presence des ions h#+. Des guides optiques planaires ont ete realises et leurs proprietes optogeometriques (profil des indices de refraction, epaisseur du guide) caracterisees par spectroscopie de modes. Leur stabilite thermique a ete etudiee et le resultat tres satisfaisant obtenu reconforte l'interet technologique de la realisation de guides d'ondes optiques par implantation de protons. Les coefficients electrooptiques des guides implantes h#+ ont ete mesures, et aucune degradation significative en fonction de la dose implantee n'a ete observee

Ce travail est centre sur la protonation enantioselective d'un acide aryl propionique, le ketoprofene. L'originalite de notre approche reside dans l'utilisation de supports insolubles chiraux de type acrylamide dont la chiralite est portee par la maille meme du polymere. Dans ce cas, le ketoprofene lie au support par un bras achiral se trouve entoure de pendants chiraux qui exercent une induction asymetrique supramoleculaire. Ainsi, en utilisant le pendant chiral (r)-methyl benzylamine, nous avons obtenu dans des conditions de controle thermodynamique, le ketoprofene de configuration s avec 60% d'ee. En revanche, les essais de deracemisation du ketoprofene supporte soit en utilisant des bases chirales et des donneurs chiraux de proton soit par double induction, base chirale-pendant chiral, n'ont pas permis d'ameliorer les exces enantiomeriques

Ce travail est centre sur la synthese asymetrique par deracemisation d'un acide 2-arylpropionique: le ketoprofene. L'originalite de notre approche reside dans l'utilisation de nouveaux inducteurs chiraux, supportes ou non. La deracemisation en phase solide du ketoprofene ou de l'un de ses precurseurs (le ketonitrile) nous a permis d'obtenir ces molecules avec des exces enantiomeriques allant jusqu'a 42%. La deracemisation en phase homogene du ketoprofene a ete envisagee selon deux principes: la protonation diastereoselective d'enolates de lithium du ketoprofene derivatise par differents inducteurs chiraux lies soit par formation d'un ester soit par formation d'une oxime, a permis d'obtenir le s-(+)-ketoprofene avec 40% d'exces enantiomerique; la protonation enantioselective du cetene correspondant au ketoprofene a permis d'obtenir (en utilisant les deux enantiomeres de notre source chirale de protons) les deux enantiomeres du ketoprofene avec des exces enantiomeriques atteignant 97% et avec un rendement superieur a 80% a partir du ketoprofene racemique

Ce travail porte sur l'étude de la capacité des 3-aminopyrrolidines (3-AP) chirales et de leurs amidures à former des complexes non-covalents avec des énolates de lithium dérivés de cyclohexanones engagés dans la réaction de protonation énantiosélective. Après une introduction portant sur les diverses méthodes d'obtention de molécules optiquement actives, un petit historique puis une bibliographie de la réaction de protonation énantiosélective sont présentes. Puis nous présentons la bibliographie de la synthèse de ces 3-AP ainsi qu'une méthode précédemment développée au laboratoire à partir de la transhydroxy-(L)-proline naturelle, et les développements apportés à cette chimie dans la perspective d'une synthèse à plus grande échelle. Une deuxième méthode d'obtention des 3-AP est également présente à partir d'un intermédiaire clé dont la synthèse avait été précédemment décrite dans la littérature. Ces 3-AP secondaires ont ensuite été mis en présence d'énolates de lithium de cétones. Trois types de complexes (amine/énolate : 1/1 ; amidure : énolate : 1/1 ou amine/amidure : énolate 1/1/1) ont été retenus. Pour chacun de ces types nous nous sommes attachés à faire varier quelques-uns des paramètres susceptibles d'influencer l'asymétrie de la réaction de protonation énantiosélective. Dans tous les cas, l'utilisation des 3-AP secondaires en tant que ligand chiral des énolates de lithium dérivés de cyclohéxanones n'a pas permis de relever la moindre induction asymétrique. La protonation par l'acide acétique de l'énolate de lithium de la 2-méthyltétralone en présence d'une 3-AP primaire, la 1-benzyl-3-(S)-aminopyrrolidine, a permis d'obtenir un e. E de 15%. Les meilleurs excès (39%) ont été relevés avec ce même énolate lorsque ce dernier, complexé avec l'amidure de lithium de la 1-benzyle-3-(S)-aminopyrrolidine et deux équivalents de bromure de lithium est protoné par deux équivalents d'acide acétique. Cette réaction est à notre connaissance, la seule impliquant un amidure d'amine primaire et un énolate lors de la protonation énantiosélective. Au cours de ce travail, l'influence directe de la qualité du MeLi. LiBr utilisé pour engendrer l'énolate a également été démontrée. L'étude RMN 13C, 1H, 6Li du complexe MeLi. LiBr a permis de caractériser les différents agrégats formés par le méthyllithium et le bromure de lithium dans le toluène comme étant des tétramères de formule brute (MeLi)4-n(LiBr)n avec n compris entre zéro et quatre. Les populations de ces cinq types de complexes ont également été déterminées.

Des nanotubes de dioxyde de titane (TiO2nts) sont étudiés comme électrodes négatives potentielles pour des microbatteries Li-ion 3D. Ces TiO2nts lisses et hautement auto-organisés sont élaborés par anodisation du Ti dans des électrolytes organiques à base de glycérol ou d'éthylène glycol contenant des ions fluor et de l'eau en faible quantité. Les structures présentant un diamètre de 100 nm et une longueur variant de 1,5 à 14 µm sont particulièrement appropriés pour l'application visée. Les TiO2nts ont été tapissés de manière conforme par un électrolyte polymère (PMA-PEG) comportant un sel de lithium (LiTFSI) grâce à la technique d'électropolymérisation. Les études morphologiques menées par SEM et TEM ont montré que les nanotubes sont entièrement recouverts d'un film mince polymère de 10 nm d'épaisseur, ce qui permet de préserver la structure 3D de l'électrode. Les tests électrochimiques portant sur les nanotubes seuls ainsi que sur les TiO2nts tapissés d'électrolyte polymère ont été effectués en demi-cellule et en cellule complète en utilisant un électrolyte polymère à base de MA-PEG contenant du LiTFSI. En demi-cellule, les TiO2nts de 1,5 µm de long delivrent une capacité surfacique de 22 µAh cm-2 relativement stable sur 100 cycles. La performance de la demi-cellule est améliorée de 45% à une cinétique de 1C lorsque les TiO2nts sont tapissés de manière conforme par un electrolyte polymère (PMA-PEG). Cet effet résulte d'un meilleur transport de charges lié à l'augmentation de la surface de contact entre l'électrode et l'électrolyte
Titania nanotubes (TiO2nts) as potential negative electrode for 3D lithium-ion microbatteries have been reported. Smooth and highly-organized TiO2nts are fabricated by electrochemical anodization of Ti foil in glycerol or ethylene glycol electrolyte containing fluoride ions and small amount of water. As-formed TiO2nts shows the open tube diameter of 100 nm and the length from 1.5 to 14 µm which are suitable for the fabrication of the 3D microcbatteries. The deposition of PMA-PEG polymer electrolyte carrying LiTFSI salt into TiO2nts has been achieved by the electropolymerization reaction. The morphology studies by SEM and TEM reveal that the nanotubes are conformally coated with 10 nm of the polymer layer at the inner and outer walls from the bottom to the top without closing the tube opening. 1H NMR and SEC show that the electropolymerization leads to PMA-PEG that mainly consists of trimers. XPS confirms the presence of LiTFSI salt in the oligomers.The electrochemical studies of the as-formed TiO2nts and polymer-coated TiO2nts have been performed in the half-cells and full cells using MA-PEG gel electrolyte containing LiTFSI in Whatman paper as separator. The half-cell of TiO2nts (1.5 µm long) delivers a stable capacity of 22 µAh cm-2 over 100 cycles. The performance of the half-cell is improved by 45% at 1C when TiO2nts are conformally coated with the polymer electrolyte. The better performance results from the increased contact area between electrode and electrolyte, thereby improving the charge transport

Cette thèse s’inscrit dans un projet comprenant 3 volets. Le premier thème porte sur l’étude de la dualité base / nucléophile bien connue dans la chimie des organolithiens (RLi). Un organolithien standard mis en réaction avec un composé carbonylé énolisable peut en effet être assimilé à une base (et ainsi déprotoner en position α du CO) et/ou un nucléophile (et alors s’additionner sur celui-ci). Notre travail vise à déterminer les principaux paramètres susceptibles d’avoir une influence sur la compétition entre ces 2 réactions. Les facteurs considérés ont été : la méthode de calcul, le degré d’agrégation, l’état de solvatation des entités, la structure du composé carbonylé et l’organolithien. Une collaboration avec l’équipe du Pr. D. C. Harrowven à Southampton est à l’origine du second volet qui porte sur l’étude théorique du mécanisme réactionnel de l’addition d’organolithiens sur des 2-cyclobutène-1,2-diones. Il est, en effet, connu que les additions d’organolithiens sur ce type de composés sont favorisées sur le carbone C1. Par contre, en présence de triflate d’ytterbium, il est possible de changer la régiosélectivité de la réaction et ainsi obtenir le produit d’addition sur le carbone C2. L’étude effectuée au niveau DFT (PBE0/ 6-31+G(d,p)) nous a permis de déterminer les paramètres responsables de la sélectivité du mécanisme d’addition C-1 ou C-2. Enfin, la dernière problématique, en collaboration avec le Pr. S. Bew (UEA Norwich), porte sur la compréhension et l’étude du mécanisme de formation d’une aziridine à partir d’un diazoacétate et d’une imine, correspondant à deux produits cis/trans
This thesis encompasses three studies led in three different research groups. The first part focuses on the dual basic and/or nucleophilic character of organolithium compounds (R-Li). These entities can trigger either a deprotonation or an addition reaction when they are brought into contact with enolisable carbonyl derivatives. Because these two pathways are fundamental to organic synthesis, their mechanisms have been the object of a sustained interest and an important corpus of experimental and theoretical data has accumulated over time. Our aim is to determine the main parameters that influence the fate of the reaction for enolisable carbonyl compounds. The factors considered are the computational method, the aggregation, the solvation state, and the carbonyl compound structure. A long-standing collaboration with the Prof. D. C. Harrowven’s team (University of Southampton) is a the origin of the second part of this thesis. It is centred on a theoretical study of the addition of an organolithium onto 2-cyclobutene-1,2-dione. It is well known that the additions of organolithium entities of this type are favoured on the carbon C1. The Harrowven’s team showed that in the presence of ytterbium triflate, the regiochemistry was changed, the adduct on the C2 carbon being obtained preferentially. The study at the DFT level has allowed us to better understand the selectivity of the C-1 or C-2 addition mechanism. The third project, led in collaboration with Prof. S. Bew (University of East Anglia), is centred on the study of the mechanism and the understanding of the origin of the selectivity of a reaction transforming a diazoacetate into a cis/trans aziridine

Mesures dans des cibles epaisses de sulfates et d'oxydes, dans des cibles minces d'oxydes disposees sur des couches minces de carbone et dans des cibles epaisses de tetraborate de li dope par equiv. A 1% de ba, la ou ce sous forme de sulfate ou d'oxyde. Bon accord avec les previsions theoriques et avec les valeurs experimentales trouvees pour des elements voisins

La déracémisation par protonation énantiosélective a permis la synthèse d'α-aminoacides optiquement enrichis et notamment de la phénylglycine. Nous avons optimisé les paramètres physiques de cette réaction afin d'en améliorer la sélectivité. Nous avons pu ainsi faire progresser l'excès énantiomérique de 57% dans le cas du N-paraméthoxybenzylidène phénylglycinate de méthyle à 70% avec un bien meilleur rendement chimique (95%). Dans une deuxième partie, nous avons appliqué le principe de la déracémisation aux acides t-Bu et Me-4 cyclohexylidène acétiques porteurs d'une chiralité axiale. Une élimination énantiosélective d'un intermédiaire prochiral halogéné par des amidures de lithium chiraux nous a permis de réaliser cette nouvelle synthèse de molécules chirales avec des sélectivités supérieures à 80%. Nous avons mis en évidence certains des paramètres régissant l'énantiosélectivité de la déracémisation et proposé des modèles rationalisant nos résultats. Nous avons aussi montré la possibilité d'un transfert d'une chiralité axiale en une chiralité centrale. De cette façon, nous avons pu accéder à l'isomère endocyclique optiquement enrichi de l'acide t-Bu-4 cyclohexylidène acétique

Ferroelectrics are dielectric materials possessing a switchable spontaneous polarization, which have attracted a growing interest for a broad variety of applications such as ferroelectric lithography, artificial photosynthesis, random and dynamic access memories (FeRAMs and DRAM), but also for the fabrication of devices for nonlinear optics, etc. All the aforementioned applications rely on the control of the ferroelectric domains arrangement, or the charge distribution and transport. In this regard, the main prerequisite is the engineering of the spontaneous polarization, obtained by reversing its orientation or locally inhibiting it. In the latter case, the interface created by the spatial discontinuity of the spontaneous polarization generates local charge accumulation, which can be used to extend the capabilities of ferroelectric materials. This thesis shows how engineering the spontaneous polarization in lithium niobate (LN) by means of proton exchange (PE), a temperature-activated ion exchange process, can be used to develop novel approaches for ferroelectric domain structuring, as well as fabrication of self-assembled nanostructures and control of ionic/electronic transport in this crystal. In particular, it is shown how the electrostatic charge at PE:LN junctions lying below the crystal surface can effectively counteract lateral domain broadening, which in standard electric field poling hampers the fabrication of ferroelectric gratings for Quasi-Phase Matching with periods shorter than 10 μm. By using such an approach, ferroelectric gratings with periods as small as ~ 8 μm are fabricated and characterized for efficient nonlinear optical applications. The viability of the approach for the fabrication of denser gratings is also investigated.  The charge distribution at PE:LN junctions lying on the crystal surface is modelled and used to drive the deposition of self-assembled nanowires by means of silver photoreduction. Such a novel approach for PE lithography is characterized for different experimental conditions. The results highlight a marked influence of the orientation of the spontaneous polarization, the deposition times, as well as the reactants concentrations and the doping of the substrate with MgO. Based on the fact that proton exchange locally reduces the spontaneous polarization, a quick and non-destructive method for imaging PE regions in lithium niobate with nanoscale resolution is also developed by using Piezoresponse Force Microscopy. Moreover the relative reduction of the piezoelectric d33 coefficient associated to PE is estimated in lithium niobate substrates with and without MgO-doping. Finally, by using advanced Scanning Probe Microscopy techniques, the features of charge transport in PE regions are further investigated with nanoscale resolution. A strong unipolar response is found and interpreted in light of ionic-electronic motion coupling due to the interplay of interstitial protons in the PE regions, nanoscale electrochemical reactions at the tip-surface interface, and rectifying metal-PE junctions.

QC 20150325

The purpose of the present thesis is to study the influence of Proton Exchange on Electric Field assisted Poling of congruent Lithium Niobate and its applications on periodically pat-terned structures. Moreover, the possibility of using Proton Exchange to avoid neighbours domains merging is studied and successfully demonstrated for period shorter than 10μm. Before approaching the poling of periodically patterned LiNbO3 samples, the main charac-teristics of the evolution of the poling of uniform samples in different masking conditions are investigated. It is well known that the kinetics of domains switching is highly dependent on the poling setup and on the quality/type of electrode employed to contact the crystal to the high voltage. We used a thin layer of Titanium both as mask for proton diffusion and as metal electrode for poling experiments. Moreover different masking configurations are pre-sented and characterized. The second part of this work deals with the periodic poling of 0.5mm-thick congruent lith-ium niobate. 9x4 mm2 1-D Ti gratings with 8.66μm and 8.03μm period were first fabricated on the +z side of the crystal and a superficial chemical pattern was reproduced via acid bath. Three different types of samples were obtained and before the poling the metallic mask was removed whereas in one configuration it was left assuring better homogeneity of the in-verted areas. The results we obtained suggest it could be possible to achieve periodically poled congruent lithium niobate gratings with period shorter than 4μm in ~500μm thick samples and hence obtain aspect ratios of more than 250.

The object of this thesis is to form an understanding of the origin of the problems associated with proton-exchanged waveguides, and to investigate possible solutions. Chapter 1 gives a brief introduction to the properties of lithium niobate, and discusses the methods available for fabricating optical waveguides in the bulk material, with particular emphasis on waveguide fabrication by the proton-exchange process. Some of the devices which have been fabricated by proton-exchange are discussed. The problems associated with proton-exchanged waveguides are reviewed. Chapter 2 deals with the physical and chemical characterisation of proton-exchanged waveguides fabricated using neat benzoic acid melts. The extent of proton-exchange is determined as a function of fabrication time and temperature using optical waveguide prism-coupler measurements, infrared absorption spectroscopy, and atomic absorption spectroscopy. Chapter 3 is concerned with the problem of waveguide mode-index stability. Using a hydrogen isotopic-exchange reaction, the extent of which is obsrved via infrared absorption spectroscopy, information on the (room-temperature) mobility of protons within the guiding layer is obtained for waveguides fabricated using neat benzoic acid melts. The recently reported process of fabricating waveguides in lithium niobate by deuterium-exchange is investigated. The behaviour of proton-exchanged and deuterium-exchanged waveguides with respect to reaction with atmospheric water vapour is investigated, and the optical properties of deuterium-exchanged waveguides are studied. In Chapter 4, a study of annealed and dilute-melt proton-exchanged waveguides is presented. It is shown, using prism-coupler measurements and infrared absorption spectroscopy, that ennealed and dilute-melt waveguides can have very similar optical properties, depending on the amount of annealing and the lithium benzoate mole-fractions used. The extent of proton-exchange is determined with time (between 215oC and 235oC) for dilute-melt waveguides produced using lithium benzoate mole-fractions of up to 1.1%. Isotopic-exchange in annealed and dilute-melt waveguides is also investigated, both at room-temperature and at temperatures commonly used for annealing. A possible explanation for the poor optical properties of (neat-melt) proton-exchanged waveguides is given. Chapter 5 deals with a study of propagation losses (using the two-prism method) and the electro-optic effect in x- and z-cut proton-exchanged waveguides. Measurements of r33 (in proton-exchanged waveguides) and r22 (in titanium-indiffused waveguides) are carried out using an external interferometric method designed by the author. The results of Chapter 4 are used to establish a method by which losses below 0.5dB/cm and a substantially restored electro-optic effect can be achieved (using a combination of dilute-melt fabrication with post-exchange annealing). Prior to the waveguide measurements, the bulk electro-optic effect is investigated for congruent, incongruent, MgO-doped, and annealed (high-temperature) crystals. Finally, in Chapter 6, a summary of the thesis is presented, and suggestions for future work are given.

Two electrodeposited and two chemical manganese dioxides were heat-treated in an air or argon environment for 24 hours at temperatures from 120-450°C and the products were characterised by chemical analysis, XRD (X-Ray Diffraction) and FTIR (Fourier Transform Infra-Red) spectroscopy. It was found that the rate of water evolution was identical in air or argon but the weight loss was greater in argon. This was explained on the basis that the x value in MnOx increased in air but not in argon. Powder X-ray diffraction spectra of the heat-treated materials showed that there was little change in structure from 25-300°C and between 300-400°C the structure changed from a γ-phase to a β-like phase. Application of the latest structural model of γ-MnO2 in terms of de Wolff disorder and microtwinning was applied to the XRD patterns of Faradiser WSLi. It was found that there was decrease in microtwinning from 25-300°C but the amount of de Wolff disorder was essentially unchanged. Simulation of XRD patterns by taking appropriate amounts of two end-members and comparing them with one obtained experimentally showed that the transformation from γ to β like in the temperature range 300-400°C was heterogeneous. FTIR spectra of the same materials showed a progressive shift of the peaks associated with the MnO6 octahedral framework. Comparison of the peak positions with the published data of ramsdellite (γ-MnO2) and pyrolusite (β-MnO2) suggested a ramsdellite phase in the unheated material and a pyrolusite phase at 400°C. An electrodeposited MnO2 was heat-treated at 200, 300 and 400°C and then H was chemically inserted using propan-2-ol or hydrazine hydrate. XRD spectra showed that a homogeneous reduction occurred with the material that had been heat-treated at 200°C and reduced with propan-2-ol while a heterogeneous reduction occurred with the material heat treated at 400°C and reduced with hydrazine hydrate. Within these extremes of behaviour different regions of homogeneity/heterogeneity were observed. With hydrazine hydrate heterogeneity set in at a lower level of H insertion than with propan-2-ol reduction. This was because the rate of reduction was faster with hydrazine hydrate and the critical value of r = 0.8 in MnOOHr was reached earlier at the surface of the MnO2 particles. FTIR spectra of the chemically reduced materials were interpreted in terms of OH bond formation which was revealed by the appearance of peaks centred at 2050 and 2650 cm-1. With the homogeneous reduction there was no evidence of OH bond formation until MnOOH0.8, in the heterogeneous reduction OH bond formation was observed at low levels of H insertion. The onset of OH bond formation was thought to be due to the localisation of the inserted H+ and eO. H insertion into a range of chemical manganese dioxides heat-treated analogously to EMD was carried out. The non heat-treated CMD material exhibited the largest region of homogeneous H insertion while H insertion for the material heat-treated at 400°C was entirely heterogeneous. Between these extremes of behaviour intermediate levels of homogeneity/heterogeneity were observed. The crystal structure of the most reduced materials formed a similar range of intergrowth structures as was found for the EMD materials. This was δ-MnOOH for the material heat-treated at 200°C and manganite for that heat-treated at 400°C. The boundaries of the homogeneous/heterogeneous behaviour of EMD and CMD were compared and it was found that heterogeneity occurred at a higher level of H insertion for the CMD materials. A range of chemically Li-inserted MnOOLix (0<_x<_0.8) compounds were prepared from an EMD and CMD that had been heat-treated at 200, 300 and 400°C and then reduced in an argon-filled glove box using n-butyllithium. Powder X-ray diffraction revealed that the first stage of the reaction (0<_x<_0.3) was homogeneous and for x>0.3 (EMD) and x>0.35 (CMD) a new phase was formed via a heterogeneous reaction. The X-ray diffraction patterns of the new phase could be indexed to an orthorhombic unit cell and, in contrast to H insertion, the crystal structures of the most reduced Li-inserted materials seemed to be the same regardless of the initial heat-treatment temperature. A novel applied linear regression analysis was developed to determine possible peak movement in a spectral dataset. The analysis used the coefficient of determination R2 as a parameter for peak movement. In the second part of the analysis it was found that a low value of R2 indicated peak movement. In the XRD patterns of EMD heat-treated at 200°C and reduced with propan-2-ol the low values of R2 correlated with peak movement. Conversely with EMD heat-treated at 400°C and reduced with hydrazine hydrate there was little or no peak movement and the values of R2 were close to 1.

Planar z-cut LiTaO$ sb3$ waveguides were fabricated by proton-exchange in pyrophosphoric acid and post-exchange annealing. Their refractive index profiles were measured, and the index profile parameters were related to fabrication conditions. This data will be useful for the design and fabrication of single and multi-moded waveguides and devices.
A step function was found to accurately model the index profile after proton-exchange. Empirical equations relating the waveguide depth $d sb{pe}$ and the extraordinary index increase $ Delta n sb{e}$ to the exchange temperature and time were found. Propagation losses were measured, and index instabilities were detected.
The generalized Gaussian function can be used to accurately model the index profile throughout annealing. Empirical equations relating the depth d and the surface index increase $ Delta n sb{s}$ to the anneal time were found. Additional empirical relations, establishing the dependence of the parameters of the equations on the anneal temperature and proton-exchange conditions, were also found. A criterion for eliminating index instabilities in the waveguide was established, and propagation losses were measured. Mathematical modelling and numerical simulation of annealing was attempted in order to gain insight into the phenomenon of the surface index increase.
Proton-exchange with buffered melts offer the possibility of fabricating waveguides with index profiles that are not possible if using concentrated melts.

Thesis (M.Sc. (Chemistry)) --University of Limpopo, 2007
The biochemical mechanism of apoptosis induced by lithium remains unclear, although there is evidence suggesting the involvement of Bax and Bcl-2. Bcl-2 family of proteins play a critical role in the regulation of apoptosis in various tumour cell lines. This pathway may be altered in cancer cells. We have used calyculin-A (CL-A), an inhibitor of protein phosphatase 2A (PP2A), to investigate the mechanism by which lithium induces apoptosis in HL-60 cells. Previous studies in our laboratory established that lithium induces apoptosis of HL-60 cells at 10 mM and above; while CL-A induces apoptosis at 1 nM and above. The observed apoptotic effects were additive. These observations led to the hypothesis that lithium and CL-A exert their biological effects by acting on a similar target. It was, therefore, the aim of this study to establish whether lithium would also exert similar inhibitory effects on the apoptotic and cell cycle regulatory genes. We further aimed at delineating the effects of both lithium and CL-A on the expression profiles of apoptotic and cell cycle regulatory genes. In this study, HL-60 cells were treated with lithium, CL-A and the combination of both. This was followed by the assessment of cell proliferation and viability at specific time points, using Coulter Counter and trypan blue dye exclusion assay, respectively. Concentrations of lithium at 10 mM and 20 mM were found to inhibit cell proliferation and exerted modest effects on cell viability in a time- and dose-dependent manner. Likewise, CL-A inhibited cell proliferation and viability in a time- and dose-dependent fashion. The combination of lithium and CL-A showed additive inhibitory effects on the growth of HL-60 cells. Further, semi-quantitative RT-PCR analyses of apoptotic (bax and bcl-2) and cell cycle regulatory genes (cdc2 and cyclin-B1) were determined. Our data revealed an under-expression of bcl-2 mRNA and an up-regulation of bax mRNA in HL-60 cells treated with lithium, CL-A and the combination of both. In addition, the expression levels of cdc2 mRNA remained constant, while cyclin-B1 mRNA expression levels were up-regulated after 24 h in HL-60 cells that were treated with cytotoxic concentrations of lithium and CL-A alone. Furthermore, the combination of lithium and CL-A showed an up-regulation of cyclin-B1 mRNA while cdc2 mRNA levels remained constant in both treated and untreated HL-60 cells. To corroborate the RT-PCR data, we present evidence by Western blot analysis that Bcl-2 family of proteins and cell cycle regulatory genes indeed play a critical role in the regulation of apoptosis in HL-60 cells. Western blot analysis revealed a down-regulation of Bcl-2 under all treatment conditions. However, lithium and CL-A alone failed to show any detectable expression levels of both Bax and cyclin-B1 proteins. In contrast, the combination of both lithium and CL-A showed an up-regulation of Bax and Cdc2 proteins in HL-60 cells. These findings suggest that the molecular mechanism elicited by lithium, CL-A and the combination of both on the growth inhibition of HL-60 cells involves an aberrant expression of apoptotic and cell cycle regulatory genes. In addition, these observations may allude to a notion that both lithium and CL-A may be used and administered successfully as positive alternative anticancer drugs.
the National Research Foundation,and the University of Limpopo Research and Administration

ALe rôle du cation co-transporté dans le mécanisme de couplage énergétique de la mélibiose perméase d'E. Coli a été analysé en étudiant les propriétés du cycle de transport en présence et en absence d'énergie et lorsque la perméase fonctionne selon un mode de symport proton, sodium ou lithium/sucre. Il est démontré qu'en plus d'un rôle régulateur de l'affinité de la perméase pour le sucre co-transporté, le cation contrôle la stabilité du complexe ternaire cation/sucre/perméase et par voie de conséquence, régule la vitesse de dissociation des co-substrats vers le compartiment cytoplasmique. Le champ électrique transmembranaire active la réaction de transport en déstabilisant le complexe ternaire cation/sucre/perméase. Ces données sont utilisées pour proposer un mécanisme de couplage énergétique de type conformationnel. Au plan moléculaire, la protéine de transport a été identifiée par marquage radioactif à l'aide d'un système d'expression in vivo. De plus, l'importance fonctionnelle de chacun des 7 résidus histidines de la perméase a été analysée en utilisant une technique de mutagenèse dirigée. Le remplacement individuel de chacune des histidines par une arginine démontre que seule l'histidine 94 est importante pour la fonction de transport. De plus, les substitutions d'une asparagine ou glutamine à l'histidine 94 indiquent que les propriétés de protonation/deprotonation de ce résidu ne sont pas impliquées dans le mécanisme moléculaire de co-transport cation-sucre de la mélibiose perméase. Ces observations excluent toute participation de systèmes de relais de charge du type de celui proposé récemment pour la lactose perméase. D'autre part, différentes mutations effectuées sur l'acide glutamique 361, localisé dans une région du transporteur en contact avec le cytoplasme, entrainent une inactivation de l'étape de translocation des co-substrats sans modifier leur reconnaissance par le transporteur

L'objectif de ce travail consistait a etudier les reactions de deracemisation en utilisant pour l'etape de reprotonation des donneurs de proton chiraux supportes sur polymere en vue d'obtenir de bons exces enantiomeriques meme a temperature ambiante. Nous avons choisi comme modele la deracemisation des 2-hydroxyacides, ce qui nous a conduit dans un premier temps a mettre au point une methode simple et precise de determination par hplc de la purete optique de ces composes. Nous avons synthetise plusieurs donneurs de proton chiraux supportes sur polystyrene ou polyacrylamide et les avons testes dans la reprotonation a temperature ambiante de l'enolate d'une dioxolanone obtenue a partir de l'acide mandelique. Or, l'enolate est instable. Nous l'avons remplace par l'ether d'enol silyle correspondant nettement plus stable. Nous avons pu montrer l'apport du support dans ce type de reaction puisqu'un exces enantiomerique de 94% a ete obtenu a -40c alors qu'a cette meme temperature le meme donneur de proton non supporte ne donne aucun exces enantiomerique

Le présent travail visait à développer et à étudier une nouvelle méthode de fabrication des guides d'onde, « High Index Soft Proton Exchange » (HISoPE) , qui permet de réaliser des guides d'onde très confinés (dne = 0,1). Des caractérisations en génération d’harmonique localisée ont montré que les propriétés non linéaires de ces guides ne sont pas détruites mais les guides HISoPE réalisés sur coupe Z peuvent présenter des modes ayant des pertes élevées. Ces pertes peuvent être éliminés en utilisant des bains plus acides pour l’échange, mais cela implique des déformations plus importante dans les guides d'onde canal et la nature hybride des modes propageant. Dans le cadre du projet PhoXcry, nous avons essayé de réaliser un modulateur électro-optique très efficace en combinant des cristaux photoniques et des guides HISoPE sur coupe X. Dans les meilleurs guides d'onde fabriqués sur coupe X, les pertes à la propagation, expliquées par la nature hybride des modes sont de 1.75dB/cm, mais dans les guides d'ondes nanostructurés il n’a pas été possible d’identifier clairement une bande interdite photonique. HISoPE en combinaison avec l’échange inverse (Reverse Proton Exchange, RPE) a montré un grand potentiel pour la fabrication de guides d'onde enterrés. Dans une expérience de SHG et malgré des pertes élevées de 2dB/cm, nous avons pu estimer une efficacité de conversion de 160%/W*cm2. Un comportement du coupleur directionnel a été observé dans les guides d'onde enterrés fabriqué en raison d’une cinétique RPE différente dans les différentes parties du guide d'onde. Un développement ultérieur de la méthode HISoPE + RPE devrait permettre d'améliorer la qualité des guides enterrés
The present work aimed to develop and to study a new method of waveguide fabrication, High Index Soft Proton Exchange (HISoPE), which allows realizing highly confining waveguides in LiNbO3 (dne=0.1). Characterizations by localized SHG experiments, showed that the nonlinear properties of the HISoPE waveguides are not destroyed, but modes with high propagation loss were observed for planar HISoPE waveguides on Z-cut wafers. These losses can be eliminated by performing the exchange in more acidic bath, but this results in more important deformations in channel waveguides and in the hybrid nature of the propagating modes. In the frame of the project PhoXcry, we tried to realize a highly efficient electro-optical modulator by combining photonic crystals and HISoPE waveguides on X-cut wafers of LiNbO3. The losses of the waveguides fabricated on X-cut, attributed to the hybrid nature of the propagating modes, were estimated to be around 1.75dB/cm. The nanostructured waveguides exhibited high losses and it was not possible to identify clear optical band gap. HISoPE in combination with reverse proton exchange (RPE) showed a great potential for buried waveguide fabrication. We used them in a SHG experiment and despite elevated losses of 2dB/cm, the conversion efficiency was estimated as high as 160%/W*cm2. A directional coupler behavior was observed in the buried waveguides due to different RPE kinetics in different parts of the waveguide. A further development of the HISoPE+RPE process will improve the quality of the buried waveguides

Le travail decrit dans ce memoire porte sur l'etude experimentale de l'interaction de protons avec une surface de fluorure de lithium a incidence rasante et a une energie de collision du kev. Nous nous sommes interesses aux mecanismes de perte d'energie du projectile et d'emission d'electrons secondaires. Nous avons mis au point une technique de multi-coincidence originale basee sur l'utilisation d'un faisceau pulse et d'un ensemble de multi-detecteurs a galette de microcanaux. Parmi ceux-ci, seize detecteurs collectent les electrons secondaires, ils sont situes sur une hemisphere entourant la cible et forment un systeme de detection de grande acceptance angulaire. Un autre detecteur sensible en position, utilise avec un deflecteur electrostatique, sert a collecter les particules diffusees analysees en charge et en angle de diffusion. Pour chaque collision, nous mesurons l'energie de toutes les particules detectees, a partir de leur temps de vol repere par rapport au signal du hacheur. Nous pouvons alors, pour chaque etat de charge de la particule diffusee, determiner les correlations entre sa perte d'energie et le nombre et l'energie des electrons secondaires. Bien que la perte d'energie et l'emission electronique apparaissent etroitement liees au niveau de la trajectoire de la particule diffusee, les resultats montrent qu'il existe un canal de perte d'energie ne donnant pas lieu a l'emission secondaire. Ce canal a ete identifie comme etant du a l'excitation des electrons de valence vers des excitons de surface. A basse energie, ce mecanisme est responsable de la majeure partie de la perte d'energie des protons incidents. Finalement, les resultats montrent que la formation de l'ion negatif est le processus d'extraction des electrons de valence, l'emission secondaire resultant quant a elle du detachement dans le vide de l'ion negatif
The work described in this thesis deals with the experimental study of the interaction of protons with a surface of lithium fluoride at grazing incidence and at a collision energy of the KeV. We are interested in the mechanisms of the projectile's energy loss and the secondary electrons emission. We have developed an original multi-coincidence technique based on the use of a pulsed beam and a set of micro-channelled multi-detectors. Of these, sixteen detectors collecting the secondary electrons are located on a hemisphere surrounding the target and form a large acceptance angular detection system. Another position-sensitive detector, used with an electrostatic deflector, serves to collect the diffused particles analysed in charge and diffusion angle. For each collision, we measure the energy of all detected particles, from their time of flight with reference to the chopper signal. We can then, for each state of charge of the scattered particle determine the correlations between its energy loss and the number of emitted secondary electrons. Although the loss of energy and the electronic emission appear closely related to the trajectory of the scattered particle, results show that there is another energy loss channel, which does not give rise to secondary electron emission. This channel was identified as being due to excitation of valence electrons to surface excitons. At low energy, this mechanism is responsible for most of the energy loss of the incident protons. Finally, results show that the formation of the negative ion is the process of extracting the valence electrons from lithium fluoride, the secondary emission resulting in the detachment in vacuum of the negative ion

Ce travail est consacré à l'étude et la réalisation des guides optiques distribués par un échange protonique partiel (PPE, Partiel Proton Exchange) localisé dans un guide de titane (Ti) diffusé dans un substrat de niobate de lithium (PPE-Ti:LiNbO3), permettant ainsi l'inscription à travers un masque de structures périodiques et apériodiques, appelées souvent 'structures de Bragg'. Le niobate de lithium est choisi comme substrat de base en raison de ses multiples propriétés attractives pour la réalisation de filtres optiques accordables électro-optiquement et offrent ainsi l'opportunité de contribuer au déploiement d'architectures optiques dynamiques. La simplicité et la maitrise du processus d'échange protonique permet d'une part de reproduire n'importe quel motif à travers un masque et de contrôler les paramètres caractéristiques de la fonction de transmission, d'autre part. Nous proposons une approche analytique originale basée sur les méthodes des rayons et de l'indice effectif permettant de calculer les constantes de propagation du guide. Elle sera utilisée pour calculer l'indice effectif de n'importe quel profil d'indice de réfraction, en particulier, pour le cas du guide distribué PPE-Ti:LiNbO3. Deux méthodes de calcul numériques sont proposées. La première considère que l'indice effectif est constant suivant la direction de propagation dans chacune des zones de la micro-structuration, alors que la deuxième, plus conforme à la réalité, tient compte du fait que l'indice effectif varie également suivant cette direction. L'effet du recouvrement entre les zones voisines de la structure, ayant subi le processus d'échange protonique, est pris en considération pour le calcul sa fonction de transmission. Nous montrons que la technique d'échange protonique permet de contrôler, par exemple, la bande passante de la fonction de filtrage et ce par le biais des paramètres caractéristiques du processus d'échange. Dans le cadre des réalisations expérimentales, nous montrons qu'une correction du rapport cyclique de la micro-structure, définissant le masque photolithographique, est obligatoire pour ne pas perdre son effet le par recouvrement des zones échangées. Des simulations et des tests expérimentaux ont permis de montrer la faisabilité d'une telle implémentation pour des structures dédiées à un fonctionnement autour de ? = 1,55 µm. Les approches qui ont été développées ont permis notamment d'établir les limites de cette technologie

A major limitation of acousto-optic (AO) leaky-mode modulator based holographic displays is their inability to present full-parallax. We propose that full-parallax capabilities can be bestowed on these displays by integrating an electro-optic (EO) phased array into the architecture. We validated this concept by rendering computational models and by fabricating and testing a basic two-axis AO/EO deflector prototype in lithium niobate. This was, to our knowledge, the first instantiation of an integrated, hybrid AO/EO deflector. The prototype had a 6° deflection range along the AO-axis, and a 3° deflection range along the EO-axis. A series of models provide us with a clear path forward for optimizing this deflector. They suggest that an AO/EO modulator with an EO deflection range of 24.5° and that requires less than 7.5 V can be fabricated within the limitations of standard photolithography.

In this dissertation, I will present the various work I have accomplished in regards to the design, simulation, and fabrication of holovideo and holodeck display technology. This includes: 1) design and analysis of a wavelength division multiplexing LiNbO3 waveguide device, 2) loss characterization and reduction (by way of reverse proton exchange) 3) design of a curved, near-eye AR display, and 4) a basis for acoustic holodeck technology (meant to service a system built from our optical devices). All these accomplishments represent, in concert, a manifestation of LiNbO3's capacity to serve as the building material central to modern holovideo displays. It is my hope that many future technologies will be built using these waveguides as their base.

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Dissertação (Mestrado em Tecnologia Nuclear)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Exemple de l'application en biologie des détecteurs solides de traces: localisation quantitative de la réaction nucléaire 6 lithium (neutron, alpha) 3 hydrogène dans l'étude du transfert placentaire du lithium, au cours du développement embryonnaire de la souris. Recherche des conditions d'obtention de détecteurs à bas mouvement propre dans le but d'appliquer la technique à la détection d'autres éléments tels que l'azote et l'oxygène

This thesis examines the effects of nerve growth factor (NGF) and lithium on the regulation of neurotensin/neuromedin N (NT/N) gene expression in PC12 pheochromocytoma cells. In PC12 cells, the expression of the rat NT/N gene is strictly dependent on simultaneous exposure to combinations of NGF, glucocorticoids, activators of adenylate cyclase, and lithium. Transient transfection experiments indicated that a consensus AP-1 site located within the NT/N promoter is the principal target of NGF and lithium action. NGF rapidly, but transiently, induces the expression of several AP-1 genes in PC12 cells, suggesting that the effect of NGF on NT/N gene expression results from increased AP-1 activity. These results led to the prediction that the induction of NT/N gene expression should be rapid, transient and dependent on de novoprotein synthesis. These experiments also suggested that the NT/N gene is principally regulated through the initiation of transcription. However, post-transcriptional mechanisms may also be involved. Experiments in this thesis were designed to examine the regulatory mechanisms responsible for increased NT production in PC12 cells when treated with different inducer combinations and whether AP-1 factors could act as mediators in responses to NGF and lithium. Results described in this thesis indicate that the principal mechanism by which NGF and lithium regulate NT biosynthesis is by activating NT/N gene transcription. Comparison of NT/N mRNA, pro NT/N synthetic rates, proNT/N proteins and mature NT levels in induced PC12 cells, demonstrated that NGF and lithium had no effect on the translation of NT/N mRNA and had only a modest effect on post-translational processing. Nuclear run-on assays showed that NT/N transcription is transicntly activated in maximally induced cells. A rapid RNase protection assay was developed to examine both the kinetics of NT/N gene activation and whether activation requires newly synthesized proteins. Quantitation of nuclear NT/N precursor RNA. using a probe spanning the junction between exon onc and intron one, provides a sensitive measure of NT/N gene activity and by several criteria provides an accurate measure of NT/N transcription. When either NGF or lithium was combined with dexamethasone and forskolin, nuclear NT/N precursor RNA transiently accumulated, although each inducer displayed different kinetics, rapid and delayed, respectively. De novo protein synthesis was not required for activating NT/N transcription when NGF was used as the permissive agent, although newly synthesized proteins secm to be needed for subsequent down-regulation. The response to lithium displayed a marked requirement for new protein synthesis, consistent with the involvement of newly synthesized AP-1 factors. RNA blot analysis showed that lithium either alone or in combination with dexamethasone and forskolin induced c-jun and fra-1 gene expression with delayed kinetics, consistent with c-Jun/Fra-1 complexes mediating the effects of lithium on NT/N gene transcription. The pathway identified by lithium does not activate or require protein kinase C. This pathway is also active in neuronally-differentiated PC12 cells suggesting that it could be involved in the regulation of NT/N gcne exprcssion in the intact nervous system. These results and order of addition experiments demonstrate that NGF and lithium activate distinct pathways required for NT/N gene induction.

L'étude des différents paramètres affectant l'énantiosélectivité de la protonation a permis d'obtenir des enrichissements optiques élevés et de dégager l'influence préponderante de la structure de l'espèce amionique intermédiaire (solvant, cation associé, amine libre de l'amidure). Dans le cas de la benzoïne, la protonation conduit initialement à l'ènediol qui s'isomérise lentement en benzoïne optiquement active. Ce résultat constitue le premier exemple expérimental de tautomérisation énantiosélective d'une forme énolique en cétone

Introdução: A epilepsia do lobo temporal mesial (ELTM) é a forma mais comum de epilepsia na população adulta, tendo a esclerose hipocampal como principal substrato neuropatológico. Uma elevada proporção dos pacientes com ELTM apresentam história familiar positiva para a epilepsia, sugerindo a participação de fatores genéticos nesta síndrome. O citoesqueleto neuronal é essencial para os processos fisiológicos das células nervosas e crises epilépticas parecem afetar esta estrutura. O citoesqueleto neuronal possui importantes componentes regulatórios, dentre eles as proteínas associadas aos microtúbulos do tipo 2 (MAP2) e tau. Objetivos: Avaliar a densidade neuronal (células imunomarcadas com NeuN), neobrotamento das fibras musgosas (por histoquímica de neo-Timm) e a expressão imunohistoquímica das proteínas MAP2 e tau no hipocampo de casos cirúrgicos de ELTM (subtipos familiar e esporádico) e controles. As mesmas análises foram conduzidas no modelo animal de lítiopilocarpina. Métodos: Casos ELTM (n=38) foram divididos em ELTM familiar (n=20) e ETLM esporádica (n=18). Hipocampos controles (n=10) foram provenientes de necrópsias de sujeitos sem histórico de problemas neurológicos. No modelo animal de lítio-pilocarpina, animais submetidos ao status epilepticus (SE) foram sacrificados nos seguintes tempos pós-SE: 1, 7, 15 e 60 dias e classificados como grupos SE1, SE7, SE15 e SE60. Animais controle foram injetados com salina. Resultados: O grupo ELTM apresentou menor densidade neuronal que o controle nas regiões da camada granular, hilo, CA4, CA3, CA1 e prosubículo. O grupo ELTM mostrou maior valor de cinza da histoquímica de neo-Timm na camada granular, molecular interna e molecular externa e maior espessura do neobrotamento axonal na camada molecular interna em relação ao grupo controle. O grupo ELTM esporádica teve maior valor de cinza da histoquímica de neo-Timm e tendência à maior espessura do neobrotamento que o grupo ELTM familiar na camada molecular interna. O grupo ELTM apresentou menor expressão de MAP2 que o grupo controle no hilo, CA4, CA3, CA1 e prosubículo e maior expressão que o controle na camada granular, CA2 e parasubículo. O grupo ELTM esporádica teve maior expressão de MAP2 que o grupo ELTM familiar em CA1 e córtex entorrinal. O grupo ELTM apresentou maior expressão de tau que o grupo controle nas regiões da camada granular, hilo, CA3, CA2 e córtex entorrinal. O grupo ELTM esporádica demonstrou menor imunorreatividade para tau que o grupo ELTM familiar no córtex entorrinal. No modelo de lítio-pilocarpina, os grupos submetidos ao SE apresentaram menor densidade neuronal e maior neobrotamento que o grupo salina. Quanto à expressão de MAP2, os grupos SE60 e SE15 apresentaram maiores valores de expressão que os demais grupos em todas as regiões analisadas. A expressão de tau em CA3 não foi diferente entre os grupos animais analisados. Conclusão: Nossos resultados existem perda neuronal, reorganização sináptica das fibras musgosas e alterações na expressão de proteínas MAP2 e tau no hipocampo de pacientes com ELTM. Dentre os casos ELTM, encontramos diferenças no neobrotamento de fibras musgosas e na expressão de MAP2 e tau entre os grupos ELTM familiar e esporádica, indicando que estes grupos se apresentam de forma distinta em relação à epilepsia. Encontramos resultados II semelhantes em relação à densidade neuronal e o neobrotamento de fibras musgosas entre pacientes com ELTM e no modelo experimental. Porém, em relação à expressão das proteínas MAP2 e tau, encontramos algumas diferenças entre humanos e animais com ELTM. Nossos resultados sugerem que apesar do modelo de epilepsia induzida por lítio-pilocarpina ser relevante para o estudo da ELTM humana e mimetizar importantes aspectos neuropatológicos, a correspondência quanto à expressão de algumas proteínas estruturais não é completa. Estudos adicionais de expressão de proteínas do citoesqueleto em outros modelos animais de ELTM serão de grande importância para o melhor entendimento do processo epileptogênco.
Introduction: Mesial temporal lobe epilepsy (MTLE) is the most common form of epilepsy in adults and has hippocampal sclerosis as the main pathological substrate. A high proportion of patients with MTLE have positive familial history for epilepsy, suggesting the involvement of genetic factors in this syndrome. Seizures may affect the neuronal cytoskeleton, an structure that is essential in the physiological processes of nerve cells. Components of the neuronal cytoskeleton include microtubule-associated protein type 2 (MAP2) and tau. Objectives: Our aim was to evaluate neuronal density, mossy fiber sprouting and immunohistochemical expression of MAP2 and tau in the hippocampus of surgical cases of MTLE (familial and sporadic subtypes) and controls. The same analysis were conducted in the MTLE lithiumpilocarpine animal model.Methods: MTLE cases (n = 38) were divided into familial MTLE (n = 20) and sporadic MTLE (n = 18). Control hippocampi (n = 10) were obtained from autopsies of subjects without history of epilepsy. In the lithium-pilocarpine animal model, male Wistar rats were submitted to status epilepticus (SE) and were killed at the following post-SE days: 1, 7, 15 and 60, and were further classified SE1, SE7, SE15 and SE60. Control animals were injected with saline. Results: MTLE showed decreased neuronal density than controls in the granular layer, hilus, CA4, CA3, CA1 and prosubiculum. MTLE group showed increased neo-Timm gray value in the granular layer, inner and outer molecular layer, as well as increased mossy fiber length of mossy fiber in the inner molecular layer when compared to controls. Sporadic MTLE specimens exhibited increased inner molecular layer gray value than familial MTLE. MTLE hihppocampi showed decreased MAP2 expression in the hilus, CA4, CA3, CA1 and prosubiculum. In the granular layer, CA2 and parasubiculum, MAP2 expression was higher in MTLE specimens than in controls. CA1 and entorhinal cortex from sporadic MTLE hippocampi showed increased MAP2 expression than familial MTLE. Tau expression was increased in the granular layer, hilus, CA3, CA2 and entorhinal cortex of MTLE specimens. Sporadic MTLE exhibited lower tau immunoreactivity in the entorhinal cortex than familial MTLE. In the lithiumpilocarpine animal model, rats submitted to SE presented lower values of neuronal density and mossy fiber sprouting than controls. SE15 and SE60 showed increased MAP2 expression in all hippocampal subfields. Tau expression in CA3 was not different among the groups. Conclusion: Our results indicate that besides neuronal loss and axonal sprouting, MTLE specimens also exhibit dendritic abnormalities related to MAP2 expression. Increased tau immunoreactivity in epileptogenic hippocampi indicates possible abnormal expression related to mossy fiber sprouting in chronic MTLE. We found differential sprouting, MAP2 and tau expression between sporadic and familial MTLE. It is possible that different genetic background might result in somehow distinct neuropathological substrates between the two MTLE subtypes, although their clinical manifestation is quite similar. While neuronal loss and axonal sprouting profiles in human MTLE and chronic phase of the lithium-pilocarpine animal model are comparable, we could not find corresponding results regarding MAP2 and tau expression. IV Several studies have shown that chemo-convulsant as pilocarpine and kainic acid result in widespread brain epileptic discharges, which are different from the more focal hippocampal discharges seen in human MTLE. Despite its limitations, the lithium-pilocarpine model stands as an important and widely used animal model of epilepsy. Besides that, other animal models in which ictal discharges and lesions are more limited to the hippocampal formation might better mimic what we see in human MTLE.

A via canônica Wnt/beta-catenina regula várias funções em vertebrados, incluindo diferenciação de células T, bem como a proliferação, sobrevivência, morfogênese e migração de vários tipos celulares. As células T CD4+ é fundamental para a competência imunológica. Foi observado pelo nosso grupo que células T CD4+ humanas apresentam ativação da via Wnt/beta-catenina após tratamento com sais de lítio ou outros agonistas da via. A ativação desta via induziu a proliferação de células T CD4+ naive e de memória central. Em conjunto, estes dados sugerem um importante papel da via Wnt/beta-catenina na homeostase de células T CD4+ humanas. Seria importante avaliar o papel da via Wnt/beta-catenina nas células do sistema imune no modelo murino, já que pouco se sabe sobre seu efeito na homeostase de células T CD4+ murinas. A ativação da via Wnt/beta-catenina pode ser induzida com inibidores da proteína Glicogênio sintase quinase 3beta (GSK3beta), por exemplo, os sais de lítio (LiCl e Li2CO3) e inibidores específicos (SB, CHIR) em vários tipos celulares. Neste trabalho, avaliamos o efeito de inibidores de GSK3? na ativação da via Wnt/beta-catenina canônica em esplenócitos e células T CD4+, através da realização de experimentos in vivo e in vitro, avaliando a expressão de seus genes alvo HIG2, Bcl-xL, Ciclina D1 e c-myc. Verificou-se que o tratamento in vivo agudo (2-12 h após a administração) ou crônico (administração diária por 30 dias) de camundongos não é capaz de ativar a via Wnt/beta-catenina in vivo em células esplênicas e células T CD4+, embora o mesmo tratamento induza a expressão dos genes alvo da via no tecido cerebral (córtex e hipocampo). Além disso, também não foi possível verificar ativação da via em esplenócitos e células T CD4+ após tratamento in vitro das mesmas com LiCl ou os inibidores específicos de GSK3beta testados(CHIR99021, SB-216763), embora essa ativação tenha sido observada na linhagem celular HEK293. Nossos resultados sugerem que a via Wnt/beta-catenina (canônica) não é induzível em células T CD4+ murinas maduras, com os agonistas testados. Isso pode ter implicações fisiológicas, por exemplo sobre a homeostase de células T CD4+, já que a proliferação homeostática de células T, influenciada em humanos pela via Wnt/beta-catenina, é menos importante em camundongos
The Wnt/beta-catenin pathway regulates many functions in vertebrates, including T cell differentiation, as well as proliferation, morphogenesis and migration in different cell types. CD4+ T cells play is fundamental for immunological competence. Our group has observed that human CD4+ T cells present activation of the Wnt/beta-catenin pathway after treatment with lithium salts or other pathway agonists. The activation of this pathway induced proliferation in naive and central memory CD4+ T cells. Together, these results suggest an important role for the Wnt/beta-catenin pathway in the homeostasis of human CD4+ T cells. It would be very important to evaluate the role of the Wnt/beta-catenin pathway in T cells in the mouse model, since little is known about its effect in mice CD4+ T cell homeostasis. The activation of the Wnt/beta-catenin pathway may be induced with Glycogen Synthase Kinase 3B (GSK3beta) inhibitors, i.e., lithium salts as mentioned above, and specific GSK3beta inhibitors (SB, CHIR) in different cell types. In this work, we evaluated the effect of GSK3beta inhibitors in the activation of the canonical Wnt/beta-catenin in splenocytes and CD4+ T cells, by conducting experiments in vivo and in vitro, evaluating the expression of its target genes HIG2, Bcl-xL, Cyclin D1 and c-myc. We verified that acute (2-12 hours after administration) or chronic (daily administration for 30 days) treatment of mice with lithium salts is not able to activate the Wnt/beta-catenin pathway in splenocytes and CD4+ T cells, although we could observe activation in brain tissues (cortex and hypothalamus). Besides, no activation of the Wnt/beta-catenin pathway was observed in these cell types after in vitro treatment with LiCl or the specific inhibitors of GSK3beta (CHIR99021, SB-216763), while the pathway was activated by the same treatments in HEK293 cells. Our results suggest that the Wnt/beta-catenin pathway is not inducible in murine mature CD4+ T cells with the tested agonists. This may have physiological implications, for instance on the homeostasis of CD4+ T cells, where homeostatic proliferation - influenced the Wnt/beta-catenin pathway in human T cells - is less important in the maintenance of the murine peripheral T cell pool

O lítio é freqüentemente utilizado no tratamento do Transtorno Bipolar, doença associada a um risco aumentado para demência. Evidências experimentais sugerem efeitos neuroproterores do lítio. O lítio inibe a amiloidogênese e a fosforilação da proteína tau tanto in vitro como in vivo. Estes são processos importantes na patogênese da doença de Alzheimer. O objetivo este estudo foi a investigação do efeito do lítio na prevalência de Transtorno Cognitivo Leve e doença de Alzheimer em 114 bipolares idosos eutímicos. Todos os sujeitos completaram uma avaliação catamnéstica, psicopatológica e cognitiva que incluía o mini-exame do estado mental (Mini-mental), o teste cognitivo de Cambridge (CAMCOG) e o questionário do informante sobre o declínio cognitivo do idoso (IQCODE). Foi feita uma comparação da prevalência de Transtorno Cognitivo Leve e doença de Alzheimer entre pacientes em uso de lítio e pacientes em uso de outros estabilizadores de humor. Os sujeitos que entraram na pesquisa tinham em média 68,2 ± 5,0 anos e preenchiam os critérios da Décima Revisão da Classificação Internacional de Doenças e Problemas de Saúde Relacionados (CID-10) para o transtorno bipolar. Durante a avaliação os bipolares estavam eutímicos. Eutimia foi definida como uma pontuação máxima de 7 pontos na escala de Hamilton de 21 pontos para Depressão e 4 na escala de Young para mania. 66 pacientes em uso contínuo do lítio por 6 anos em média foram comparados com 48 pacientes em tratamento com outros estabilizadores de humor. O diagnóstico de Transtorno Cognitivo Leve foi feito de acordo com os critérios de Petersen(1999) e de doença de Alzheimer de acordo com o critério do “National Institute for Communicative Disorders and Stroke - Alzheimer’s Disease and Related Disorders Association” (NINCDS/ADRDA). A prevalência de demência nesta amostra (19,4%) foi mais elevada do que o esperado para uma população comparável (7,1%). A prevalência de doença de Alzheimer entre aqueles com lítio foi 4,5% quando comparada com 33,3% entre aqueles sem lítio. Controlando idade e outras variáveis relacionadas ao curso da doença, o efeito do lítio na prevalência de doença de Alzheimer permaneceu significativo (OR = 0,079; p < 0,001). Nenhuma associação foi encontrada com Transtorno Cognitivo Leve. A alta da prevalência de doença de Alzheimer neste estudo está de acordo com as evidências de risco aumentado para demência em pacientes bipolares. Nesta amostra o tratamento com lítio reduziu a prevalência de Alzheimer aos níveis da população idosa em geral. Estes achados estão de acordo com os efeitos neuroprotetores do lítio em eventos cruciais para a patologia da doença de Alzheimer. Estudos prospectivos são necessários para avaliar se o lítio também pode ser efetivo na prevenção de doença de Alzheimer em outras populações.
Lithium is widely used in the treatment of bipolar disorder, a condition associated with an increased risk for dementia. Experimental evidence suggests that lithium has a neuroprotective effect. Both in vitro and in vivo, lithium inhibits amyloidogenesis and phosphorilation of tau protein, which are two crucial processes in the pathogenesis of Alzheimer’s disease. The objective of this study was to investigate the effect of lithium on the prevalence of Mild Cognitive Impairment and Alzheimer’s disease in 114 elderly euthymic bipolar patients. Subjects completed a thorough catamnestic, psychopathological and cognitive tests evaluation including the Mini-mental state evaluation, Cambridge cognitive test (CAMCOG) and the informant questionnaire on cognitive decline in the elderly (IQCODE). The prevalence of Mild Cognitive Impairment and Alzheimer’s disease between patients on lithium therapy and patients on treatment with other mood-stabilizing drugs was compared. Patients were 68.2 ± 5.0 years old and fulfilled of the International Classification of Diseases - 10th Revision (ICD-10) diagnosis for bipolar disorder. At the time of the evaluation patients were euthymic, as defined by a maximum score of 7 in the 21-item Hamilton Rating Scale for Depression, and 4 in the Young Mania Rating Scale. Sixty-six patients were continuously being treated with lithium for six years, on average, and 48 patients were receiving other mood-stabilizing drugs. Diagnosis of Mild Cognitive Impairment was made according to Petersen (1999) and of Alzheimer’s disease was made according to the National Institute for Communicative Disorders and Stroke - Alzheimer’s Disease and Related Disorders Association (NINCDS/ADRDA) criteria. The overall prevalence of dementia in our sample (19.4%) was higher than the prevalence expected in the age-comparable general population (7.1%). The prevalence of Alzheimer’s disease among lithium users was 4.5% as compared to 33.3% among non-users. After controlling for age and other variables related to the clinical course of the bipolar disorder, the effect of lithium on Alzheimer’s disease prevalence remained significant (OR = 0.079; p < 0.001). No association was found with Mild Cognitive Impairment. The higher prevalence of Alzheimer’s disease in our study supports the reports of increased risk for dementia in bipolar patients. In our sample, lithium treatment reduced the prevalence of Alzheimer’s disease to the levels of the general elderly population. This finding is in line with the neuroprotective effects of lithium on crucial events for the pathology of Alzheimer’s disease. Further prospective studies are needed to clarify whether lithium may also be effective in the prevention of Alzheimer’s disease in the general population.

Introdução: Diversas evidências apontam para um papel da disfunção mitocondrial no Transtorno de Humor Bipolar (THB), mas pouco se sabe sobre isso no THB de início recente. Na mitocôndria a atividade da cadeia transportadora de elétrons (CTE) atua juntamente com o ciclo do ácido cítrico na produção de energia, mas não está claro se estão alteradas no THB. O DNA mitocondrial (DNAmt) codifica diversas proteínas da CTE e está associado ao estresse oxidativo, mas nunca foi avaliado em pacientes no THB in vivo. O estresse oxidativo está associado ao THB e à disfunção mitocondrial, mas não se sabe muito das atividades das enzimas antioxidantes no THB de início recente. O óxido nítrico (NO) é uma molécula com efeitos neuromoduladores, mas com um papel no THB ainda não elucidado. O lítio é um tratamento padrão-ouro no THB, tendo mostrado efeitos neuroprotetores. Apesar disso, pouco se conhece do efeito do lítio na CTE, nas enzimas do ciclo do ácido cítrico, no conteúdo de DNAmt e na regulação de NO em humanos. Também não está claro o papel antioxidante do lítio no THB. Metódos: Pacientes com THB em depressão (n=31), não medicados em sua maioria (84%), foram tratados por 6 semanas com lítio. Antes e depois do tratamento, verificaram-se em leucócitos as atividades dos complexos I-IV da CTE, atividades das enzimas citrato sintase, succinato desidrogenase e malato desidrogenase e também o conteúdo de DNAmt; em plasma foram analisados os níveis de NO, substâncias reativas ao ácido tiobarbitúrico (TBARS) e as atividades de catalase (CAT), glutationa peroxidase (GPx), superóxido dismutase (SOD) e razão de SOD/CAT. Os pacientes com depressão bipolar foram comparados com 28 controles saudáveis. Resultados: Em comparação com controles, os pacientes com THB tiveram um aumento de GPx (p < 0,001) e CAT (p=0,005) e uma diminuição de SOD/CAT (p=0,001), sem outras diferenças nos demais biomarcadores. Pacientes com THB I mostraram uma diminuição de citrato sintase (p=0,02) e uma discreta diminuição do conteúdo de DNAmt (p=0,05) em comparação com o THB II; o conteúdo de DNAmt esteve ligeiramente diminuído no THB I comparado com controles (p=0,05). Do início ao fim do tratamento com lítio houve aumento da atividade do complexo I da CTE (p=0,02), diminuição de TBARS (p=0,02) e SOD (p=0,03) e aumento de NO (p=0,02), sem haver alteração de outros parâmetros. Depois do tratamento, o TBARS se mostrou diminuído em respondedores comparados a não respondedores (p=0,02) e diminuído no THB II em comparação com o THB I (p=0,04). Discussão: No THB de início recente, houve poucas alterações em biomarcadores. Os achados sugerem aumento de CAT e GPx na depressão bipolar de início recente e uma diminuição de conteúdo mitocondrial no THB I comparado com o THB II, que devem ser confirmadas por outros estudos. Os resultados reforçam um papel neuroprotetor do lítio, sugerindo que a droga aumente a atividade do complexo I da CTE mitocondrial e aumente os níveis de NO na depressão bipolar. Além disso, o lítio reforçou o seu papel antioxidante e modulador das enzimas antioxidantes no THB
Background: Several evidences point to a role for mitochondrial dysfunction in Bipolar Disorder (BD), but few is known about it on short-term BD. In mitochondria the electron transport chain (ETC) acts jointly with citric acid cycle to produce energy, but it is not clear if they are altered in BD. Mitochondrial DNA (mtDNA) encodes several ETC proteins and is associated with oxidative stress, but it was never evaluated in BD in vivo. Oxidative stress is associated with BD and with mitochondrial dysfunction, but few is known about the activities of antioxidant enzymes in short-term BD. Nitric oxide (NO) is a molecule with neuromodulatory effects, but with an unclear role in BD. Lithium is a gold-standard treatment for BD, which has shown neuroprotective effects. However, few is known about lithium effect on ETC, citric acid cycle, mtDNA content, and NO regulation in humans. Also, lithium\'s antioxidant role in BD is unclear. Methods: Patients with BD depression (n=31) unmedicated in majority (84%) received lithium treatment for 6 weeks. Before and after treatment, in leukocytes the activities of ETC complex I-IV, citrate synthase, succinate dehydrogenase, and malate dehydrogenase, and mtDNA content were evaluated; in plasma, NO levels, thiobarbituric acid reactive substances (TBARS), the activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), and SOD/CAT ratio were evaluated. Bipolar depression patients were compared with 28 healthy controls. Results: When compared with controls, BD patients showed an increase in GPx (p < 0.001) and CAT (p=0.005) and a decrease in SOD/CAT (p=0.001), but showed no difference for other biomarkers. Patients with BD I showed a decrease in citrate synthase (p=0.02) and a slight decrease in mtDNA content (p=0.05) when compared to BD II; mtDNA content was slightly decreased in BD I compared to controls (p=0.05). From baseline to endpoint, there was an increase in ETC complex I activity (p=0.02), a decrease in TBARS (p=0.02) and SOD (p=0.03) and an increase in NO (p=0.02), without change in other parameters. After treatment, TBARS was decreased in responders compared to non-responders (p=0.02) and decreased in BD II compared to BD I (p=0.04). Discussion: In short-term BD few alterations were observed on biomarkers. The findings suggest increase on CAT and GPX in short-term bipolar depression and mitochondrial content decrease in BD I when compared to BD II, which deserve other studies for confirmation. The results reinforce a lithium\'s neuroprotective role and suggest that lithium increases ETC complex I activity and NO levels in bipolar depression. Moreover, lithium reinforced its role as antioxidant and as a modulator of antioxidant enzymes in BD

Kam Yuen Kwan = 利用散射及反衝粒子飛行時間譜儀及其他表面分析儀器就LiTaO3對質子及鋰離子交換後改變之研究 / 甘婉君.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2003.
Includes bibliographical references.
Text in English; abstracts in English and Chinese.
Kam Yuen Kwan = Li yong san she ji fan chong li zi fei xing shi jian pu yi ji qi ta biao mian fen xi yi qi jiu LiTaO3 dui zhi zi ji li li zi jiao huan hou gai bian zhi yan jiu / Gan Wanjun.
Acknowledgements --- p.i
Abstract --- p.iii
Table of contents --- p.viii
Chapter Chapter 1 --- Introduction --- p.1
Chapter 1.1 --- Definition of Ferroelectrics --- p.1
Chapter 1.2 --- Common Properties of Ferroelectrics --- p.2
Chapter 1.3 --- Polarization --- p.2
Chapter 1.4 --- Lithium Tantalate (LiTa03) --- p.7
Chapter 1.4.1 --- Crystal Structure --- p.8
Chapter 1.4.2 --- Pyroelectric Effect --- p.9
Chapter 1.4.3 --- Determination of Polarity --- p.10
Chapter 1.4.4 --- Proton Exchange --- p.11
Chapter 1.4.5 --- Reverse Exchange --- p.12
Chapter 1.4.6 --- Applications --- p.13
Chapter 1.5 --- Emerging Attentions in Surface Properties of Smart Materials --- p.14
Chapter 1.6 --- Difficulties in Surface Studies of Ferroelectric and Related Smart Materials --- p.15
Chapter 1.7 --- Recent Developments of TOF-SARS in Our Research Group and Its Applicability on LiTa〇3 --- p.16
Chapter 1.8 --- Objectives of the Present Thesis Work --- p.17
Chapter 1.9 --- Organization of the Thesis --- p.17
Chapter 1.10 --- Reference --- p.18
Chapter Chapter 2 --- Ion Exchange Processes and Sample Prepartion --- p.20
Chapter 2.1 --- Fundamental of Ion Exchange Technique --- p.20
Chapter 2.2 --- Sample Preparation --- p.22
Chapter 2.2.1 --- Starting Material --- p.22
Chapter 2.2.2 --- Proton Exchange Procedures --- p.23
Chapter 2.2.3 --- Reverse Exchange Procedures --- p.23
Chapter 2.3 --- Reference --- p.24
Chapter Chapter 3 --- Time-of-Flight Ion Scattering and Recoiling Spectrometry (TOF-SARS) --- p.26
Chapter 3.1 --- Introduction --- p.26
Chapter 3.1.1 --- Physics in Elemental Analysis --- p.26
Chapter 3.1.2 --- Physics in Structural Analysis --- p.29
Chapter 3.2 --- Instrumentation --- p.32
Chapter 3.2.1 --- Vacuum Chamber --- p.33
Chapter 3.2.2 --- Pumping System --- p.35
Chapter 3.2.3 --- Sample Manipulator --- p.35
Chapter 3.2.4 --- Pulsed Ion Beam Line --- p.36
Chapter 3.2.5 --- Detectors and Associated Electronics --- p.37
Chapter 3.3 --- Reference --- p.39
Chapter Chapter 4 --- Other Surface Science Tools Used in This Work --- p.41
Chapter 4.1 --- Fourier Transform Infrared Spectroscopy (FTIR) --- p.41
Chapter 4.1.1 --- Principle of FTIR --- p.41
Chapter 4.1.2 --- Experiment --- p.42
Chapter 4.1.3 --- Attenuated Total Reflectance (ATR) Mode of FTIR --- p.44
Chapter 4.2 --- X-Ray Photoelectron Spectroscopy (XPS) --- p.45
Chapter 4.2.1 --- Basic Principle of XPS --- p.45
Chapter 4.2.2 --- Experimental Set Up --- p.48
Chapter 4.3 --- Elastic Recoil Detection (ERD) --- p.49
Chapter 4.3.1 --- Basic Theory of ERD --- p.49
Chapter 4.3.2 --- Experimental Set Up --- p.50
Chapter 4.4 --- Scanning Electron Microscope (SEM) --- p.51
Chapter 4.4.1 --- Working Principle of SEM --- p.52
Chapter 4.4.2 --- Experimental Set Up --- p.52
Chapter 4.5 --- Reference --- p.53
Chapter Chapter 5 --- Results and Discussions --- p.54
Chapter 5.1 --- ERD Results on Incorporation of Protons --- p.54
Chapter 5.2 --- XPS Results on Proton Exchange and Reverse Exchange --- p.56
Chapter 5.3 --- FTIR Results on Proton Exchange and Reverse Exchange --- p.57
Chapter 5.4 --- SEM Results on Domain-Inversion Induced by Proton Exchange --- p.59
Chapter 5.5 --- TOF-SARS Results on Enhancement of Ion-induced Electron Emission by Proton Exchange --- p.61
Chapter 5.5.1 --- Typical TOF-SARS Spectra - Data from Molybdenum Sample (Mo) Holder --- p.61
Chapter 5.5.2 --- Virgin LiTa03 (0001) --- p.62
Chapter 5.5.3 --- Possible Mechanism for the Variation of O(S) and the Electron Emission Yield --- p.65
Chapter 5.5.4 --- The Use of O(S) Peak to Calculate the Potential Built Up upon a Change of Temperature --- p.67
Chapter 5.5.5 --- TOF-SARS Data from the Proton and Lithium-ion Exchanged LiTa03 (0001) --- p.69
Chapter 5.5.6 --- Plausible Mechanisms of Enhancement of Ion-induced Electron Yield induced by Proton Exchange --- p.70
Chapter 5.6 --- Additional Discussions of the TOF-SARS Data on LiTa03 and Other Relevant Experiments --- p.75
Chapter 5.6.1 --- Additional Discussion of the Nature of the Electron Peaks --- p.75
Chapter 5.6.2 --- Additional Experiments on Azimuthal Angle (δ) Scans --- p.77
Chapter 5.6.2.1 --- Data from Platinum (Pt) (111) as a Reference Test --- p.77
Chapter 5.6.2.2 --- Azimuthal Angle Dependence of Ion-induced Electron Emission from Proton-ion Exchanged LiTa03 (0001) --- p.78
Chapter 5.7 --- Reference --- p.80
Chapter Chapter 6 --- Conclusion --- p.83
Chapter Chapter 7 --- Appendix --- p.86
Chapter 7.1 --- Caption --- p.86
Chapter 7.2 --- Figures --- p.90

碩士
國立臺灣大學
光電工程學研究所
94
In this thesis, optical waveguides and directional couplers are made by proton exchange and annealed proton exchange process on Z-cut lithium niobate(LiNbO3), and are operated at blue-laser wavelength with single mode. In particular, process characteristics, output field countours, coupling length of directional coupler, and photorefractive effect caused by blue laser are discussed. Optical mode simulation is based on the beam propagation method with refractive index models of proton exchange and annealed proton exchange waveguides, and waveguides with different conditions are discussed. In experiment, annealed proton exchanged waveguides supporting single mode at blue-laser wavelength are fabricated. The experimental results of waveguide width agree quite well with that obtained by simulation. Moreover, directional coupler is fabricated and measured under the single-mode process condition, Experimental data show the coupling length is 0.441mm when the waveguide width is 2.8um and the gap is 3.5um. Photorefractive effect is also measured for straight waveguides and directional couplers. Experimental results reveal that photorefractive effect of proton exchanged waveguides are less significant in comparison with that of Ti-diffused waveguides. The coupling ratio of directional coupler with a coupling length of 1600um is varied from 0.152 to 0.175 due to photorefractive effect.

by Loi Kwok Kwong.
Thesis (M.Phil.)--Chinese University of Hong Kong, 1992.
Includes bibliographical references (leaves 197-222).
Chapter Chapter 1 --- Introduction --- p.1
Chapter 1.1 --- An Overview of Integrated Optics --- p.1
Chapter 1.2 --- Application of Lithium Niobate Integrated Optical Circuit --- p.4
Chapter 1.3 --- Summary --- p.5
Chapter Chapter 2 --- Optical Waveguide Theory --- p.7
Chapter 2.1 --- Introduction --- p.7
Chapter 2.2 --- Ray Optics Treatment of Planar Waveguide --- p.7
Chapter 2.2.1 --- Step-index Waveguide --- p.8
Chapter 2.2.2 --- Graded-index Waveguide --- p.13
Chapter 2.3 --- Optical Channel Waveguide --- p.20
Chapter 2.3.1 --- Marcatili's Method --- p.22
Chapter 2.3.2 --- Effective Index Method --- p.26
Chapter 2.4 --- Summary --- p.30
Chapter Chapter 3 --- Waveguide Fabrication Technology --- p.32
Chapter 3.1 --- Properties of Substrate Materials --- p.32
Chapter 3.1.1 --- Glass --- p.32
Chapter 3.1.2 --- Semiconductor --- p.34
Chapter 3.1.3 --- Ferroelectric Material --- p.35
Chapter 3.2 --- Waveguide Fabrication Techniques --- p.40
Chapter 3.2.1 --- Ion Implantation --- p.40
Chapter 3.2.2 --- Titanium Indiffusion --- p.41
Chapter 3.2.3 --- Proton Exchange --- p.44
Chapter 3.3 --- Summary --- p.48
Chapter Chapter 4 --- Fabrication and Measurement of Optical Waveguides --- p.49
Chapter 4.1 --- Fabrication of Optical Waveguides --- p.49
Chapter 4.1.1 --- Planar Waveguides --- p.49
Chapter 4.1.1.1 --- Substrate Cutting --- p.49
Chapter 4.1.1.2 --- Substrate Cleaning --- p.49
Chapter 4.1.1.3 --- Proton Exchange --- p.50
Chapter 4.1.1.4 --- Post-exchange Annealing --- p.51
Chapter 4.1.2 --- Channel Waveguides --- p.51
Chapter 4.1.2.1 --- Patterning Technique: Photolithography and Lift-off --- p.51
Chapter 4.1.2.2 --- Proton Exchange and Annealing --- p.56
Chapter 4.1.2.3 --- Lapping and Polishing --- p.56
Chapter 4.2 --- Measurement of Waveguide Parameters --- p.57
Chapter 4.2.1 --- Coupling of Light into Optical Waveguide --- p.57
Chapter 4.2.1.1 --- Prism Coupling --- p.58
Chapter 4.2.1.2 --- End-fire Coupling --- p.60
Chapter 4.2.2 --- Effective Index --- p.63
Chapter 4.2.3 --- Refractive Index Profile --- p.63
Chapter 4.2.4 --- Waveguide Depth --- p.67
Chapter 4.2.5 --- Propagation Loss --- p.67
Chapter 4.2.6 --- Near-field Intensity Profile --- p.69
Chapter 4.3 --- Summary --- p.74
Chapter Chapter 5 --- Results and Discussions --- p.75
Chapter 5.1 --- Proton-exchanged Waveguides Using Phosphoric Acid --- p.75
Chapter 5.2 --- Proton-exchanged LiNb03 Waveguides Using Toluic Acid --- p.112
Chapter 5.3 --- Proton-exchanged LiNb03 Waveguides Using Stearic Acid --- p.127
Chapter 5.4 --- Proton-exchanged LiNb03 Waveguides Using Cinnamic Acid --- p.148
Chapter 5.5 --- Structural Characteristics of Proton-exchanged Waveguides --- p.174
Chapter 5.5.1 --- Thermogravimetric Analysis --- p.174
Chapter 5.5.2 --- Raman Spectroscopy --- p.174
Chapter 5.5.3 --- Infrared Spectrometry --- p.179
Chapter 5.5.4 --- Double Crystal X-ray Diffractometry --- p.185
Chapter 5.6 --- Summary --- p.190
Chapter Chapter 6 --- Conclusions --- p.192
References --- p.197
Chapter Appendix 1 --- Error Estimations --- p.219
Chapter Appendix 2 --- List of Publications --- p.221

Tese de mestrado integrado em Engenharia Biomédica e Biofísica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2017
A técnica de Ressonância Paramagnética Eletrónica, RPE (EPR do inglês Electron Paramagnetic Resonance) utiliza métodos de espectroscopia para a deteção de eletrões livres - ou radicais livres - em moléculas cuja estrutura cristalina permite a retenção e estabilização destes radicais. Os radicais livres formam-se, entre outras causas, devido à exposição das moléculas a radiação eletromagnética de energia considerável sendo a quantidade de radicais formados e retidos na molécula proporcional à dose de radiação absorvida por esta. Esta relação é o principio básico da RPE e diz-nos que através da contabilização dos radicais formados, por espectroscopia, é possível inferir acerca da dose radiativa absorvida por uma molécula, sendo este o principal objetivo da dosimetria. Apesar da utilização da RPE para fins de dosimetria em radioterapia ser uma aplicação relativamente recente, trata-se de uma técnica já muito bem estabelecida em outras áreas. Em particular, a técnica RPE com dosímetros de alanina é mesmo recomendada pela Agência Internacional de Energia Atómica (IAEA do inglês International Atomic Energy Agency) não só para fins de dosimetria retrospetiva como também para a medição de doses de radiação superiores a 6 Gy. As vantagens da utilização de alanina como material dosimétrico recaem na estabilidade dos seus radicais, na resposta linear num intervalo alargado de dose e no facto de ser um material cujas características de dispersão e absorção de radiação ionizante serem muito semelhantes às dos tecidos corporais. No entanto, apesar de todas as vantagens, a baixa sensibilidade da alanina não permite a sua utilização para a medição e verificação de doses inferiores a 6Gy, comummente utilizadas em tratamentos radioterapêuticos. Deste modo, foram estudados diversos materiais para encontrar o dosímetro mais adequado que, mantendo as características vantajosas da alanina, colmatasse o problema encontrado. A melhor alternativa encontrada foi o formato de lítio que apresenta uma sensibilidade quase sete vezes superior à da alanina e uma maior equivalência à água no que respeita os coeficientes de absorção massa-energia em dose de radiação relevantes em tratamentos de radioterapia. Por conseguinte, o sistema de RPE com dosímetros de formato de lítio começou a ser considerado como uma melhor opção e diversos testes de caracterização têm vindo a ser realizados para aferir acerca da qualidade, estabilidade e adequabilidade desde novo sistema a várias aplicações em radioterapia. O sistema em questão foi aplicado, com sucesso, para verificações dosimétricas em tratamentos de Radioterapia Externa como radioterapia de intensidade modulada (IMRT) ou radioterapia conformacional tridimensional (3D-CRT), em que doses de cerca de 2 Gy por dia – dependendo do plano de tratamento - são depositadas no tumor do paciente por um feixe de fotões produzidos num acelerador linear, e em tratamentos de Braquiterapia, em que radioisótopos são colocadas dentro ou próximo do alvo do tratamento. Em ambos os casos o sistema dosimétrico de formato de lítio mostrou ser robusto, ter uma resposta linear às diferentes doses absorvidas e permitir determinações das doses com uma incerteza inferior a 2.5 %. Assim, mesmo não sendo uma técnica considerada para uso diário em clínicas, devido ao moroso processo de leitura do sinal de RPE, o sistema de dosimetria RPE de formato de lítio torna-se uma das mais vantajosas alternativas aos sistemas utilizados atualmente em aplicações em que a obtenção de medições de alta precisão é priorizada relativamente à eficácia de tempo, tendo já sido considerado um ótimo candidato para auditorias de dosimetria nas técnicas estudadas. No entanto, apesar das elevadas expectativas, nenhuma investigação tinha sido ainda realizada relativamente ao funcionamento do sistema de formato de lítio após irradiação com partículas mais pesadas como protões, cujas interações com a matéria são consideravelmente diferentes das dos fotões. Apesar do número de clínicas especializadas em terapia de protões ser relativamente reduzido devido aos elevados custos associados e, por conseguinte, a oferta deste tratamento ser ainda limitada, trata-se de uma alternativa à radioterapia convencional, com claras vantagens no que diz respeito à precisão e eficácia do tratamento que advêm principalmente da deposição de energia característica dos protões e do associado pico de Bragg, cuja profundidade de ocorrência é definida pela energia inicial dada às partículas. Os protões entram no novo meio com uma energia muito elevada e uma taxa de depositação de energia reduzida mas, com o aumento da profundidade e a diminuição da energia da partícula, esta taxa de deposição aumenta gradualmente, atingindo o seu máximo na profundidade do pico de Bragg, onde toda a restante energia das partículas é depositada e as partículas ficam em repouso, não depositando mais energia. Assim, controlando a profundidade do pico de Bragg, a maior dose pode ser depositada na área tumoral e os órgãos e tecidos envolventes podem ser poupados, evitando-se os danos colaterais associados à radioterapia convencional. Deste modo, é de extrema importância a existência de um sistema de dosimetria de elevada qualidade que permita, com elevada precisão, a verificação das doses de radiação entregues pelos feixes de protões utilizados, devendo o sistema RPE ser considerado para esta aplicação. O trabalho de investigação apresentado nesta dissertação foi realizado com o objetivo de aferir acerca das características do sistema RPE com formato de lítio após irradiações de protões e da influência que a diferente deposição de energia e interações destas partículas com a matéria podem ter no sistema em questão. A investigação e consequente caracterização foi feita relativamente a dois tópicos principais: a taxa de resposta do sinal de RPE obtido pelos dosímetros aquando submetidos a doses de radiação entre os 0 Gy e os 9 Gy, através da obtenção e análise da curva Dose-Resposta do sistema, e do estudo do desvanecimento do sinal durante um período de um mês. Adicionalmente foi realizado um “teste cego” a fim de verificar a exatidão conseguida na estimação da dose absorvida por um dosímetro somente através do seu sinal RPE e da curva Dose-Resposta. Este trabalho de investigação foi realizado na Universidade de Linköping, na Suécia, em parceria com a recente clínica de terapia de protões Skandionkliniken, em Uppsala (Suécia), onde todas as irradiações de protões foram realizadas. Os resultados confirmaram a elevada qualidade e precisão do sistema para verificações dosimétricas em terapia de protões. A curva Dose-resposta mostrou uma relação linear entre o sinal de RPE dos dosímetros e a dose absorvida por estes pelo que um maior sinal corresponde a uma maior dose absorvida pelo respetivo dosímetro. A elevado valor do coeficiente de correlação de Pearson entre as variáveis foi interpretada como um forte indicador da qualidade das estimações que se obteriam através da relação encontrada e isto foi confirmado no teste às cegas em que, utilizando apenas dois grupos de dosímetros para determinar a curva de Dose-Resposta, a dose desconhecida fornecida a um terceiro grupo de dosímetros foi estimada com um erro de somente 1 %, apenas com base nos seus sinais de RPE e na regressão obtida. Relativamente ao estudo do desvanecimento do sinal, cada grupo de dosímetros foi irradiado em semanas consecutivas durante um mês, tendo o sinal de RPE de todos os dosímetros sido medido no final desse mês, no mesmo dia. Os resultados foram evidentes: os sinais de RPE dos dosímetros cujas irradiações decorreram nas primeiras semanas da experiência sofreram um desvanecimento maior, tendo sido registado um desvanecimento máximo na ordem dos 6.50 % durante o período de tempo estudado. Este fenómeno, que não havia sido verificado nos sinais de dosímetros sujeitos a radiação de fotões, constitui assim um dos mais importantes fatores a ter em conta aquando da utilização do sistema para verificações dosimétricas neste tipo de irradiações com feixes de protões. Após os testes efetuados, é possível afirmar que o sistema de dosimetria RPE com formato de lítio mostrou ser robusto e bastante eficaz em verificações dosimétricas também nesta aplicação. No entanto, e apesar de uma análise mais extensa deste fenómeno ser necessária, foi comprovado o desvanecimento do sinal de RPE com o tempo pelo que o intervalo de tempo decorrido entre a irradiação e a leitura do sinal do dosímetro se torna num elemento preponderante e determinante na medição de doses absorvidas com a maior precisão possível. Assim, apesar de poderem ser necessárias algumas correções aos sinais obtidos no espectrómetro, quando a leitura destes sinais não é imediata à irradiação, o potencial deste sistema é inquestionável, devendo o sistema RPE com formato de lítio ser visto como um forte candidato a ser usado, por exemplo, em auditorias de dosimetria em terapia de protões.
Electron Paramagnetic Resonance (EPR) dosimetry using lithium formate dosimeters started to be studied as an alternative to the well-established dosimetry method that uses alanine as dosimeter material, so that a higher precision and accuracy in the measurements of low absorbed doses commonly used in radiation therapy could be achieved. Lithium formate has shown to be a material with properties very similar to alanine and thus very suitable for EPR dosimetry, but with the advantage of being up to seven times more sensitive to smaller radiation doses. The proposed dosimetry system was tested in both external beam therapy (photon therapy) and in brachytherapy and the system showed to be very robust, allowed dose determinations with a standard uncertainty lower than 2.5 % and was considered a good candidate for dosimetry audits in both radiotherapy modalities. The next step and the aim of the present dissertation work is the study and characterization of the lithium formate system under proton beam irradiations. The use of heavy charged particles is associated to very different interactions of the energy with matter and, consequently, to different dose deposition processes that may influence the dosimetry system performance. So, despite the suitability of the system for the other clinical applications, no assumptions can be made about the system quality for dose measurements in proton therapy. In this way, the system was studied regarding two main characteristics: the dose response and the phenomenon of signal fading. This research work was mainly based in Linköping University (Sweden) but it involved a partnership with Skandionkliniken in Uppsala (Sweden) to perform the necessary proton irradiations. The first test studied the relation between the EPR signals and the absorbed dose and the results showed that not only the obtained regression that characterizes that relation is, as expected, linear but also allowed absorbed dose to water estimations with an average estimation uncertainty below the 2 %. To complement this test and to verify what accuracy could be reached with a linear regression estimated with only two groups of dosimeters, a group of four dosimeters was irradiated with an unknown dose that was further estimated with an error of 1 %, confirming the great determinations that can be achieved with the present dosimetry system. The second study indicated that, after proton irradiations, the EPR signal stored in the lithium formate dosimeters decreases with time and, for a period of 31 days, a maximum fading of 6.50 % was discovered. This phenomenon is not unexpected in irradiations with heavy particle beams and needs to be considered if the irradiation and the EPR signal measurement are not done in the same day because if a smaller signal than the one associated to the real absorbed dose is considered, erroneous conclusions will be consequently taken regarding the absorbed dose by the dosimeter. Overall, though more studies need to be done, especially regarding the fading associated to the dosimeters EPR signals, the lithium formate dosimetry system is considered a very promising tool for dose verifications in proton beam irradiations. The system not only presents a linear behaviour as it allows dose estimations with uncertainties lower than the 4 % uncertainty limit accepted in dose delivery processes. Therefore, the lithium formate dosimetry system might actually be a good candidate for audits in proton radiation therapy.

There is a drive for improving the surface uniformity of optical waveguide devices in the photonics lab. This report focuses on the exploration of annealed proton exchange (APE) waveguide fabrication on lithium niobate crystal as a method of producing optical waveguides. These waveguides aim to have little variation in step height or surface roughness in the transition area from the waveguide location to that of the bulk crystal, providing a uniform surface amenable to vertical device integration. This is a substantial improvement over the titanium diffused waveguide process, which can have surface variations in excess of 100nm. It is anticipated that the smoother surface will enable light to couple more easily into photonic devices, such as ring resonators, as compared to the current Ti diffused waveguide process. This work explores the design and fabrication aspects of annealed proton exchange waveguides. A review of literature on modeling hydrogen diffusion into lithium niobate is presented, as well as computer models for simulating the bidimensional fractional hydrogen proton concentration distribution. This is used to determine the change in refractive index of the waveguide needed to simulate the mode propagation and profile in the device. Fabrication processes involved in proton exchange waveguide formation are outlined, and measurements for working devices are presented. Best case loss for current devices are 0.5 dB/cm. These samples exhibit smooth surfaces with only ±60A in variation of surface uniformity. Concluding remarks present ideas to further the work by lowering propagation losses, improving mode matching to single mode fiber, and improving the consistency of fabrication conditions.

碩士
國立成功大學
微電子工程研究所碩博士班
101
Long period fiber grating (LPFG) has been extensively researched and used in fiber optic communications systems, but its device applicability cannot be expanded any further due to the inherent limitations associated with the fiber such as its fixed cylindrical shape and optically linear dielectrics. In order to mitigate the fiber-entailed limitations and also to take into account for the monolithic integratibility of devices, long period gratings based on the various waveguide structures or sometime being collectively referred to as long period waveguide gratings (LPWGs) are therefore proposed. However, with the advent of integrated optical circuits, the traditional gratings functioned as filters only involve with a single wavelength, so for other device applications that involve the filtering and transmitting of multiple wavelengths such as the dense wavelength-division multiplexing (DWDM), the traditional LPWGs could hardly be proven useful! Therefore it would be wise if the LPWGs could be further improved in order to adapt to the foregoing demand. With this spirit in mind the concept of phase-shifted long-period gratings are hereby proposed, designed and fabricated in order to deliver the selective filter spectra that involve at least two rejection bands. In this thesis, highly reliable and low cost long-period waveguide gratings in LiNbO3 substrates were successfully produced using the two-step proton-exchange (PE) process. The proton source needed for the experiment was supplied by stearic acid and the grating pitch (Λ) so designed was set at 44 μm. In the first PE process, the slab waveguide cladding was formed while the temperature was controlled at 250°C for 4-hour and annealed later at 400°C for 70 min. The second step PE process was executed to form the core while the temperature was set at 250°C for 55min. The grating pitch was produced using AZ5214-E photoresist via a standard photolithographic technique. The subsequent measurements showed that the maximum dip contrast of the LPG device was about 18dB and the full width at half maximum (FWHM) was about 2.8nm. The resonant wavelength was measured to be 1549.5nm, which agreed rather well with the simulation conducted beforehand. The phase-shifted long period gratings with a finite number (M) of sections cascaded together are proposed and fabricated. It was expected theoretically and later justified experimentally that an M-section phase-shifted long period grating would produce (M-2) sidelobes between two dominant rejection bands, and the separation between the two rejection bands increased linearly with respect to M.

碩士
國立臺灣大學
光電工程學研究所
88
Waveguide bands and Y-junctions are very important elements of integrated optical devices. However, the most serious problem is that the radiation loss becomes excessive when the bending angle is larger than 1∘. In this paper, A proton-exchanged prism-like region is fabricated for the acceleration of the phase front, which facilitates the bending of the guided wave. The experimental results of waveguide bands and Y-junctions are greatly enhanced, which make the application of wide-angle waveguide bends and Y-junctions possible.

碩士
國立臺灣大學
電子工程學研究所
96
Mixed pyrophosphoric acid and adipic acid are used as the solution for protonexchange in LiNbO3. For testing, the proton exchanged areas are obtained by using various temperatures and times. Then, the exchanged areas are wet etched with mixed hydrofluoric acid and nitric acid to reveal ridge structures for optical waveguide devices. Scanning electro microscopy is then used to investigate the end faces of the ridge structures and measure the aspect ratios. Moreover, the etched surfaces are scanned by atomic force microscopy to make sure if the overall roughness is small enough for the fabrication of devices for optical communication. For optical characterization, ridge-type S-bend waveguides are fabricated for measuring the transmission ratios to confirm the optical confinement of ridge structures, experimental results show that the steeper ridge structure fabricated by the proposed proton-exchange source can give rise to larger optical transmission ratio.Moreover, the optical transmission loss is measured by the cut-back method to study the effect of surface roughness on the transmission ratio.

博士
元智大學
機械工程學系
105
ABSTRACT In this study, we prepared a lab–built water–cooled fuel cell hybrid power system. This system contains 2.7 kW proton exchange membrane fuel cells, ultracapacitors, and lithium batteries that are actually constructed in a commercial electric forklift, APT–20. This hybrid system can conform to the working state of a typical electric forklift, providing lifting loads of 1000 kg at 4 kW. This system is designed to control the fuel cell so as not to exceed its own power generating capacity of 74% in operation, so it is coupled with a fluctuating load of a set of small fuel cells to assist in balancing power. For maximum power output to the lift motor, it is coupled with a set of independent supply lift motors to increase kinetic energy and improve the overall output state. The fuel supply is a low–pressure hydrogen–storage system, consisting of four tanks of low–pressure steel hydrogen–storage cylinders to be used by the fuel cell. It thus provides a safer hydrogen–storage method for use in factory transport vehicles. By designing two sets of auxiliary power sources with different powers, it is anticipated that the fuel cell output can be maintained at 1.8 kW to 2 kW, such that the fuel cell has stable output and prolonged life–span, and can be maintained under a good working environment, and that the overall system has maximum effectiveness in supplying the necessary kinetic energy according to the usage requirements.

The research presented in this thesis focuses on developing new functional polymeric materials that can conduct ions, H+, or OH - or Li+. The motivation behind this work was to understand the similarities and/or differences in the structure property relationships between polymer membranes and the conductivity of H+ and OH - ions, and between polymer membranes and the anhydrous conductivity of H+ and Li+ ions. This understanding is critical to developing durable polymer membranes with high H+, OH - and Li+ ion conductivity for proton exchange membrane fuel cells (PEMFCs), alkaline anion exchange membrane fuel cells (AAEMFCs) and lithium ion batteries respectively. Chapter 1 describes the basic functioning of PEMFCs, AAEMFCs and lithium ion batteries, the challenges associated with each research topic, and the fundamental mechanisms of ion transport. The proton conducting properties of poly(4-vinyl-1H-1,2,3-triazole) were investigated on a macroscopic scale by impedance spectroscopy and microscopic scale by solid state MAS NMR. It was found that proton conductivity is independent of molecular weight of the polymer, but influenced by orders of magnitude by the presence of residual dimethylformamide. To improve the mechanical properties of otherwise liquid-like 1H-1,2,3-triazole functionalized polysiloxane homopolymers, hybrid inorganic-organic proton exchange membranes (PEMs) containing 1H-1,2,3-triazole grafted alkoxy silanes were synthesized, using sol-gel chemistry. This method enabled self-supporting membranes having proton conductivity comparable to uncrosslinked homopolymers. One of the biggest challenges with AEMs for use in AAEMFCs is finding a cationic polyelectrolyte that is chemically stable at elevated temperatures in high pH environment. Novel triazolium ionic salts were developed, having greater chemical stability under alkaline conditions compared to existing imidazolium ionic salts. However, the chemical stability of triazolium cations was not sufficient for AAEMFC applications. Excellent chemical stability of (C5H5)2Co+ in 2 M NaOH at 80°C over 30 days was demonstrated and polymerizable vinyl functionalized cobaltocenium monomers were synthesized. This work paves the way for future development of AEMs containing cobaltocenium moieties to facilitate hydroxide ion transport. Polymers containing covalently attached cyclic carbonates were synthesized and doped with lithium triflate and their lithium ion conductivities were investigated. The findings highlight the importance of high charge carrier density and flexibility of the polymer matrix to achieve high lithium ion conductivity. These results are similar to the key factors influencing anhydrous proton transport.