L'hydroxapatite (HA) est largement utilisée comme matériau de revêtement pour l'implant de la hanche en raison de sa bioactivité exceptionnelle. Il est également flexible et peut accueillir des ions dans sa structure. Le zinc (Zn) est un bon ion dopant comme il stimule la formation osseuse et présente des caractéristiques antibactériennes utiles qui peuvent aider à lutter contre les infections chirurgicales. Les implants de hanche revêtus d‟HA sont classiquement préparés par pulvérisation par plasma en poudre. Un processus émergent appelé projection de plasma de précurseur de solution (SPPS) est intéressant car il permet le dépôt de revêtements ayant des caractéristiques nanométriques/submicrométriques. Ce travail de recherche porte sur la fabrication de revêtements d‟HA et HA dopés Zn par SPPS. L'influence des précurseurs de solution de départ et des paramètres opérationnels du processus de projection sur les caractéristiques microstructurales d‟HA est discutée. Les mécanismes de croissance des revêtements obtenus en utilisant différents séries de précurseurs sont présentés. En outre, différents modèles sont utilisés pour décrire les propriétés mécaniques des revêtements HA par SPPS et sont corrélés à leurs microstructures. Le mécanisme de dopage en Zn à d‟HA par SPPS et son rôle pour inhiber la formation d'HA sont démontrés. Enfin, la comportement in vitro sous fluide corporel simulé (SBF) est présentée. On forme une couche d'apatite de type osseux sur la surface du revêtement HA, mais l'expérience a validé l'effet inhibiteur du Zn sur la formation d‟apatite. / Hydroxyapatite (HA) is widely used as coating material for hip implant due to its exceptional bioactivity. It is also flexible and can accommodate ions into its structure. Zinc (Zn) is a good dopant ion as it stimulates bone formation and exhibits useful antibacterial characteristics which can help fight surgical infections. HA-coated hip implants are conventionally prepared by powder plasma spraying process. An emerging process called solution precursor plasma spraying (SPPS) is an interesting one as it allows for the deposition of coatings having nanometric/ submicrometric features. This research work presents about the fabrication of HA and Zn doped HA coatings by SPPS. The influence of starting solution precursors and operational spray process parameters to the microstructural characteristics of HA is discussed. The coating build-up mechanisms of the obtained coatings using different sets of precursors are presented. Moreover, different models are used to describe the mechanical properties of the SPPS HA coatings and are correlated to their microstructures. Mechanism of Zn doping to HA by SPPS and its role for inhibiting HA formationare demonstrated. Finally, the in-vitro behaviour under simulated body fluid (SBF) is presented. Bone-like apatite layer on HA coating‟s surface is formed but the experiment validated the inhibiting effect of Zn to apatite formation.

Ces travaux ont portés sur l’élaboration de dépôts de La2Zr2O7 par projection plasma de solution (SPPS) pour une application barrière thermique pour un moteur spatial. Différentes solutions de précurseurs de solvants divers ont été formulées pour la synthèse des poudres et des différents dépôts. Les précurseurs et les solvants ont un impact important sur les interactions en solution entrainant des modifications des propriétés des poudres, particulièrement les phases cristallines ou la densification. De même, la variété des solutions étudiées et l’optimisation des paramètres de projections ont permis l’élaboration de différentes microstructures de dépôts (dense, homogène poreux et colonnaire). La microstructure colonnaire présente la meilleure résistance aux essais de cycles thermiques par rapport aux autres dépôts développés. Il a également était établie une corrélation entre les dépôts réalisés par SPPS et les données structurales des poudres. / These work deal with the conception of La2Zr2O7 coatings by Solution Precursor Plasma Spraying (SPPS) for thermal barrier application in space engine. Different precursors’ solutions of various solvents were prepared for powder synthesis and the realization of different coatings. Precursors and solvents have important effect on interactions in solution leading to the modification of powder properties, especially crystalline phases or densification. Similarly the diversity of studied solutions and the optimisation of thermal projection parameters allowed the elaboration of various coatings’ microstructures (dense, homogeneous porous and columnar). Columnar microstructure show better resistance to thermal cycling shock experiment than others coatings. It was also established a correlation between the SPPS coatings and powders structural data.

Sulfation of tyrosine residues is a post-translational modification that occurs on many secretory as well as transmembrane proteins. This modification is believed to be essential for numerous biological processes. However, one of the factors hindering the study of the significance of sulfotyrosine (sTyr) within a protein is the absence of a general method that enables the synthesis of sTyr peptides in satisfactory yields and purity. A general approach to the synthesis of sTyr-bearing peptides was developed in which the sTyr residue is incorporated into the peptides with the sulfate group protected. For the implementation of this general approach a new protecting group for sulfates, namely, the dichlorovinyl (DCV) group was developed. This was accomplished by conducting a careful analysis of the reaction of a trichloroethyl (TCE)-protected sulfate ester with piperidine and 2-methylpiperidine (2-MP). A unique sulfuryl imidazolium reagent, compound 2.22, was also developed that enabled the ready synthesis of DCV-protected sulfates. This reagent was used to prepare the amino acid building block FmocTyr(SO3DCV)OH (2.23). An alternative and more economical synthesis of FmocTyr(SO3DCV)OH (2.23) was also developed that did not require reagent 2.22. Fmoc-based solid phase peptide synthesis (SPPS) was used to incorporate 2.23 into peptides using 2-MP for Fmoc removal. After cleavage of the peptide from the support, the DCV group was removed by hydrogenolysis to give sTyr peptides in good yield and purity. Using this approach a variety of sTyr peptides were prepared including a tetrasulfated 20-mer corresponding to residues 14-33 in chemokine receptor D6 and a disulfated 35-mer corresponding to residues 8-42 of the N-terminus region of the chemokine receptor DARC and this is the largest multisulfated sTyr–bearing peptide made to date. It was also demonstrated that the incorporation of an important non-hydrolyzable sTyr analog, 4-(sulfonomethyl)phenylalanine (Smp), into peptides can be accomplished in good yield by protecting the sulfonate residue with a TCE group during SPPS. This approach was shown to be superior to the previously reported method where the sulfonate group is unprotected. Finally, a number of sulfotyrosine bearing peptides were synthesized and tested as protein tyrosine phosphatase-1B (PTP1B) inhibitors

Sulfation of tyrosine residues is a post-translational modification that occurs on many secretory as well as transmembrane proteins. This modification is believed to be essential for numerous biological processes. However, one of the factors hindering the study of the significance of sulfotyrosine (sTyr) within a protein is the absence of a general method that enables the synthesis of sTyr peptides in satisfactory yields and purity. A general approach to the synthesis of sTyr-bearing peptides was developed in which the sTyr residue is incorporated into the peptides with the sulfate group protected. For the implementation of this general approach a new protecting group for sulfates, namely, the dichlorovinyl (DCV) group was developed. This was accomplished by conducting a careful analysis of the reaction of a trichloroethyl (TCE)-protected sulfate ester with piperidine and 2-methylpiperidine (2-MP). A unique sulfuryl imidazolium reagent, compound 2.22, was also developed that enabled the ready synthesis of DCV-protected sulfates. This reagent was used to prepare the amino acid building block FmocTyr(SO3DCV)OH (2.23). An alternative and more economical synthesis of FmocTyr(SO3DCV)OH (2.23) was also developed that did not require reagent 2.22. Fmoc-based solid phase peptide synthesis (SPPS) was used to incorporate 2.23 into peptides using 2-MP for Fmoc removal. After cleavage of the peptide from the support, the DCV group was removed by hydrogenolysis to give sTyr peptides in good yield and purity. Using this approach a variety of sTyr peptides were prepared including a tetrasulfated 20-mer corresponding to residues 14-33 in chemokine receptor D6 and a disulfated 35-mer corresponding to residues 8-42 of the N-terminus region of the chemokine receptor DARC and this is the largest multisulfated sTyr–bearing peptide made to date. It was also demonstrated that the incorporation of an important non-hydrolyzable sTyr analog, 4-(sulfonomethyl)phenylalanine (Smp), into peptides can be accomplished in good yield by protecting the sulfonate residue with a TCE group during SPPS. This approach was shown to be superior to the previously reported method where the sulfonate group is unprotected. Finally, a number of sulfotyrosine bearing peptides were synthesized and tested as protein tyrosine phosphatase-1B (PTP1B) inhibitors

No description available.

Differences in the expression of antimicrobial peptides in vivo have been proposed as underlying factors influencing susceptibility to infection. In this context, the role of avian b-defensins in inhibiting avian influenza infections is a study object in an ongoing collaboration with the Zoonotic Ecology and Epidemiology group at Lnu. In this report, an attempt to synthesize two variants of the peptide Anas Platyrhynchos AvBD-8, using Fmoc-based SPPS, is described. The length of AvBD-8 (43 aa) necessitated peptide synthesis in two segments to subsequently be ligated using native chemical ligation. The first component of a 19 aa segment was thus a Dbz-linker, which would allow to ligate this end with a second segment (24 aa). Halfway through the synthesis of this larger segment the batch was split into two pots, allowing the synthesis of two segments differing by one single amino acid (R for W). The composition of these segments were: Dbz-HDTSCTGGAQKCQVANNPA (Dbz-segment), SVVTRCCPIGQKCWGFARTNPPPC(boc) (W-segment), and  SVVTRCCPIGQKCRGFARTNPPPC(boc) (R-segment). Crude product yields were 284,5 mg; 67,6% (Dbz-segment), 137,6 mg; 52,3% (W-segment), and 166,3 mg; 64,2%. Preliminary mass spectrometric analysis on the crude products did not indicate the presence of the desired segments in major mass peaks. Further product purification is necessary in order to allow definite conclusions, but it appears as if the synthesis has not worked. Possible explanations are either impure or degraded reactant(-s), folding or shielding effects of the growing peptide chain at some point inhibiting synthesis, or experimental errors during one or more of the many steps involved in the synthesis.

Since Ebbesen's seminal work in 1998 observing extraordinary optical transmission (EOT) through nanohole arrays, much research has focused on the role of surface plasmon polaritons (SPPs) in EOT. While the energy and momentum conditions have become clear, no consensus has been reached on the role of incident light polarization. This study presents a simple model that captures Bloch-SPP excitation, including the role of polarization, in general periodic plasmonic structures. Our model predicts that under certain conditions polarization conversion should occur in EOT light transmitted through the nanohole array. We experimentally measure polarization conversion in EOT and compare the experimentally obtained results to the predictions of our model. Using numerical simulations, we tie the far field experimental results to the near field underlying physics described by our model. In using polarization conversion to provide evidence supporting our model, we also establish a novel approach to achieving polarization conversion based on SPPs instead of hole shape or other techniques in literature, and present reasons why this approach to achieving polarization conversion may be better suited for applications in biomedical sensing and optical elements. / Master of Science / In 1998, Ebbesen et al¹ observed that when light is shown on a metal nanofilm perforated with nanoholes more light appears on the other side of the metal film than was incident on the nanoholes. The unexpectedly high transmission of light through the nanohole array was termed extraordinary optical transmission (EOT), and quickly found applications in diverse fields such as biomedical sensing^13,14, energy harvesting^12,31, and nonlinear optics^12–14,24 . As the importance of EOT in applications became clear, interest developed in understanding the fundamental physics involved. Over the next 20 years, researchers showed that the incident light (made up of electromagnetic fields) excites conduction electrons on the surface of the metal film¹¹ . Specifically, the light and the electrons couple to form quasiparticles known as surface plasmon polaritons (SPP) which propagate along the surfaces of the metal film. The SPPs on the back surface of the metal film then radiate free space transmitted light, which is observed as EOT. However, much of the physics involved how SPPs mediate EOT has remained unclear. The first focus of this work is theoretical, presenting a microscopic model for SPP mediated EOT. In contrast to many groups which aim to characterize SPPs from their far field properties, our model focuses on the near field microscopic physics and presents the far field properties as a consequence of the near field physics. Since the near field cannot be probed iv experimentally, we use numerical simulations to both verify our model’s predictions in the near field and predict the properties that should be measured in the far field. The second focus of this work is more applications driven. We notice that our model predicts that under certain conditions SPPs should cause a phenomenon known as polarization conversion to occur, which is when the polarization of the transmitted light is different from the polarization of the incident light. We experimentally measure the predicted polarization conversion, thereby providing substantial experimental evidence in support of our theoretical model. Our novel approach to achieving polarization conversion based on the behavior of SPPs differs substantially from the approaches in literature (usually based on hole shape²⁴). We present the reasons why our SPP-based approach to achieving polarization conversion is more robust to fabrication imperfections than the conventional approaches, and describe how our approach could affect various applications.

DC-SIGN est une lectine tétramérique impliquée dans la réponse immunitaire adaptative; Elle reconnait à la fois les ligands mannosylés et fucosylés. Bien que les interactions protéine-saccharide soient essentielles à de multiples processus biologiques, les interactions individuelles sont faibles (de l'ordre du mM), ainsi, la multivalence du ligand est nécessaire.La première partie de ce projet est la construction d'un ligand polyfucosylé de DC-SIGN. Une structure multivalente dendrimérique est choisie pour son bon contrôle de la géométrie et de l'homogénité (macroscopique et microscopique).Dans une seconde partie, la stratégie de synthèse a été adaptée à différents monomères pour produire de multiples glycodendrimères. Ceux-ci pourront donner des renseignements sur la structure la plus adaptée aux interactions avec DC-SIGN. / DC-Sign is a tetrameric lectin presents on dendritic cells involved in the adaptive immune response; It recognizes both mannosylated and fucosylated ligands. Although protein-carbohydrate interactions are essential to many biological processes, individual interactions usually exhibit weak binding affinities (mM range), thus multivalency of the ligand is required. The first part of our project is the construction of a very active yet simple fucosylated synthetic ligands for DC-SIGN. As multivalent structure, dendrimers are chosen for their good control both in geometry and in homogeneity (macroscopic and microscopic). In a second part, the synthesis strategy was adapted to different monomers to produce various glycodendrimers. They could give us information on the more adapted structure for DC-SIGN interaction.

With the recent emergence of the field of metamaterials, the study of subwavelength propagation of plane waves and the dissipation of their energy either in the form of Joule losses in the case of electomagnetic waves or in the form of viscous dissipation in the case of acoustic waves in different interfaced media assumes great importance. with this motivation, I have worked on problems in two different areas, viz., plasmonics and surface acoustics. the first part (chapters 2 & 3) of the dissertation deals with the emerging field of plasmonics. Researchers have come up with various designs in an efort to fabricate efficient plasmonic waveguides capable of guiding plasmonic signals. However, the inherent dissipation in the form of Joule losses limits efficient usage of surface plasmon signal. a dielectric-metal-¬dielectric planar structure is one of the most practical plasmonic structures that can serve as an efficient waveguide to guide electromagnetic waves along the metal-dielectric boundary. I present here a theoretical study of propagation of surface plasmons along a symmetric dielectric-metal-dielectric structure and show how proper orientation of the optical axis of the anisotropic substrate enhances the propagation length. an equation for propagation length is derived in a wide range of frequencies. I also show how the frequency of coupled surface plasmons can be modulated by changing the thickness of the metal film. I propose a Kronig-Penny model for the plasmonic crystal, which in the long wavelength limit, may serve as a homogeneous dielectric substrate with high anisotropy which do not exist for natural optical crystals. in the second part (chapters 4 & 5) of the dissertation, I discuss an interesting effect of extraordinary absorption of acoustic energy due to resonant excitation of Rayleigh waves in a narrow water channel clad between two metal plates. Starting from the elastic properties of the metal plates, I derive a dispersion equation that gives resonant frequencies, which coincide with those observed in the experiment that was performed by Wave Phenomena Group at Polytechnic University of Valencia, Spain. Two eigenmodes with different polarizations and phase velocities are obtained from the dispersion equation. at certain critical aperture of the channel, an interesting cutoff effect, which is unusual for an acoustic wave, is observed for one of the eigenmodes with symmetric distribution of the pressure field. the theoretical prediction of the coupling and synchronization of Rayleigh waves strongly supports the experimentally measured shift of the resonant frequencies in the transmission spectra with channel aperture. the observed high level of absorption may find applications in designing metamaterial acoustic absorbers.

The joining of two molecular functions or the strategy of adding functions to proteins has been tremendously important for the development of proteins as tools in research and clinic. Depending on the intended application, there are a wide variety of functions that can be added to a proteins. In clinical applications drugs are a commonly conjugated to antibodies and in research adding reporter groups such as biotin, enzymes or fluorophores is a routine procedure. The chemistries and methods most often used suffer from drawbacks such as lack of stringency, which could lead to undesired effects on the protein. Many site-specific methods of labeling of antibodies require modification or insertion of handles in the antibody recombinantly, before labeling can be performed. The core of this thesis is the development of a strategy for covalent specific labeling of antibodies by exploiting the site specific binding of the Z domain to Protein A. Photoreactive Z-domains were produced by solid phase peptide synthesis, which provides the opportunity to insert a photoreactive amino acid and a reporter biotin at specific positions in the domain. The inherited binding to the Fc-part of the antibody in combination with the incorporated photoreactive amino acid, BPA, is used for site-specific interaction, and thereafter, covalent coupling to the antibody. The exposure with the appropriate wavelength of light enables the formation a covalent linkage between the Z domain and the antibody. The biotinylated photoactivable domains were subsequently used to site-specifically label a number of different types of antibodies, polyclonal rabbit IgG, monoclonal human IgG1 and monoclonal mouse IgG2a, and thereafter the antibodies was employed in a variation of applications. The photolabeling procedure of antibodies by the use of photoactivable Z domains has proven to be successful and could serve as a valuable tool in several applications. / QC 20120507