No description available.

No description available.

No description available.

Wood is a complex biocomposite that exhibits a high work of fracture, making it an ideal model for multiphase man-made materials. Typically, man-made composites demonstrate interfacial fracture at failure due to abrupt transitions between neighboring phases. This phenomenon does not occur in wood because gradual phase transitions exist between regions of cellulose, hemicellulose, and lignin and therefore adhesion between adjacent phases is increased. The formation of interphases occurs as a consequence of the self-assembly process which governs the formation of wood. If this process was understood more thoroughly, perhaps tougher man-made, biobased composites could be prepared. To study self-assembly phenomena in wood, a system composed of a model copolymer (pullulan abietate, DS=0.027) representing the lignin-carbohydrate complex (LCC) and a model surface for cellulose fibers was used. The self-assembly of the polysaccharide pullulan abietate (DS=0.027) onto a regenerated cellulose surface prepared using the Langmuir-Blodgett (LB) technique was studied via surface plasmon resonance (SPR). Rapid, spontaneous, and desorption-resistant cellulose surface modification resulted when exposed to the model LCC. Adsorption was quantified using the de Feijter equation revealing that between 9-10 anhydroglucose units (AGUs) adsorb per nm&178; of cellulose surface area when cellulose is exposed to pullulan abietate (DS=0.027) compared to the adsorption of 6.6 AGUs per nm&178; of cellulose surface area when cellulose is exposed to unsubstituted pullulan. / Master of Science

Nanotechnology has advanced to the point that nanoparticles can now be fabricated in a broad variety of shapes from a wide range of materials, each with their own properties and uses. As the list of manufacturable particles continues to grow, a new frontier presents itself: assembling these existing nanoparticles into more complicated nanoscale structures. The primary objective of this thesis is to demonstrate and characterize one such method of nanoscale construction, the plasmonically directed self-assembly of gold nanospheres onto both silver nanospheroids and gold nanorods. At the heart of this research is a the use of a photocleavable ligand (1-(6-Nitrobenzo[d][1,3]dioxol-5-yl)ethyl(4-(1,2-Dithiolan-3-yl)butyl) carbamate), which is capable of forming a photoreactive self-assembly monolayer (SAM) on gold and silver surfaces. After photoactivation, this SAM becomes positively charged at low pH, allowing it to electrostatically bind with negatively charged gold nanospheres (or other negatively charged nanoparticles). In this thesis, I describe both a secondary photoreaction that this ligand is capable post-photocleavage, which removes the ligand's ability to bind to negatively charged gold nanospheres, allowing for, among other assembly methods, reverse photopatterning. I further show that this photocleavable ligand can be used in conjunction with gold nanospheres to create aligned, metal structures on silver nanospheroid surface by exposure to linearly polarized UV light. Similarly, I also demonstrate how the ligand can be used to preferentially bind gold nanospheres to the ends of gold nanorods with the use of ultrafast femtosecond pulsed 750 nm laser light, making use of multi-photon absorption. Both methods of self-assembly, as well as the secondary photoreaction, are dependent on the plasmonics of the metal nanoparticles. This thesis also goes into the backgrounds of plasmonics, plasmonically mediated catalysis, self-assembly, and photocleavable chemicals. / Ph. D. / Nanotechnology has advanced to the point that nanoparticles can now be fabricated in a broad variety of shapes from a wide range of materials, each with their own properties and uses. As the list of manufacturable particles continues to grow, a new frontier presents itself: assembling these existing nanoparticles into more complicated nanoscale structures. The ability to build and design such structures further advances the use of nanotechnology for medical and industrial applications. In this thesis, I describe and demonstrate a method of nanoparticle self-assembly developed by our group which uses the unique optical properties of metallic nanoparticles in conjunction with a light-activated binding chemical to control and direct the assembly of gold nanoparticles onto a silver nanosphere or gold nanorod base. The preliminary results for both of these techniques are highly promising, and I describe them in detail. I furthermore explore a secondary light-driven reaction our light-activated chemical is capable of. This secondary reaction can prevent particle binding, broadening the applications and techniques of the lightactivated binding chemical.

No description available.

Os receptores dos hormônios da tireóide (TRs) são fatores de transcrição envolvidos na diferenciação celular, metabolismo e funções fisiológicas da maioria dos tecidos. Muitos estudos mostram que diversos efeitos farmacológicos mediados pelos TRs podem ser benéficos na farmacoterapia, especialmente aqueles mediados pelo TR que podem ser úteis em condições médicas importantes como obesidade, hipercolesterolemia e diabetes. Além disso, a descoberta que o TR é a isoforma predominante no coração, mediando a maioria dos efeitos cardiovasculares prejudiciais, estimulou a pesquisa por ligantes seletivos para o TR que poderiam ser utilizados em quadros clínicos importantes com perfil de segurança aceitável. Foi realizado um estudo das relações quantitativas entre a estrutura e atividade (QSAR) de um conjunto de compostos com atividade biológica descrita para TR e TR, que gerou modelos de Holograma QSAR com elevada consistência interna e externa, apresentando bom poder de correlação e predição das propriedades biológicas. Também foi realizado um minucioso estudo de triagem virtual, que propiciou a seleção de 7 compostos que foram adquiridos para terem suas atividades biológicas avaliadas. Ensaios de transfecção e gene repórter foram estabelecidos e utilizados na avaliação da atividade biológica dos compostos selecionados pelo ensaio virtual. Finalmente, um ensaio utilizando ressonância plasmônica de superfície (SPR) foi desenvolvido e utilizado para avaliar a atividade agonista desses compostos, e que pode ser útil para avaliar a atividade de novos ligantes. A técnica de SPR também foi empregada em um cuidadoso estudo da interação do TR com seus correguladores, que incluiu estudos cinéticos e termodinâmicos, propiciando a determinação das taxas cinéticas e parâmetros termodinâmicos para a interação do complexo TR-T3 com peptídeos derivados de dois de seus correguladores. Os resultados obtidos são relevantes e devem ser considerados no planejamento de futuros experimentos utilizando o LBD de TR e agonistas. / The thyroid hormone receptors (TRs) are transcriptional factors involved in cell differentiation, development, metabolism and physiological function of most tissues. Many lines of evidence show that several pharmacological actions of TRs might be beneficial in medical therapy, specially those mediated by TR that target important medical conditions like obesity, hypercholesterolemia and diabetes. Additionally, the findings that TR is the predominant isoform in the heart and mediates most of the TRs deleterious cardiovascular effects, stimulated the research for selective TR ligands which could address important medical needs with an acceptable safety profile. In this PhD thesis, studies of the quantitative structure-activity relationships (QSAR) of a dataset of compounds with reported biologic activity for both TR and TR were performed, and statistically significant Hologram QSAR models with good predictive ability for untested compounds were created. In parallel, a careful virtual screening procedure was executed, leading to the selection of 7 compounds which were purchased for the evaluation of their biological activities. Cell transfection and reporter gene assays were developed, validated and used to evaluate the biological activities of these compounds. Finally, a surface plasmon resonance (SPR) assay was developed and used to assess the agonistic activity of these compounds. The SPR technique was also employed in a careful study of the interaction between the ligand binding domain of TR and peptides derived from its coregulators, which included the determination of the kinetic and thermodynamic parameters for this interaction. The results suggest that flexibility plays an important role in the interaction between the receptor and its coregulators, and point out important aspects of experimental design that should be addressed when using TR LBD and its agonists. Furthermore, the methodology described here may be useful for the identification of new TR ligands.

L'objectif de cette thèse est le développement d'une langue électronique avec une méthode simplifiée d'obtention de récepteurs à réactivité croisée. Ces récepteurs sont préparés par une approche combinatoire novatrice qui consiste au mélange et à l'auto-assemblage de deux disaccharides. Le couplage de ces récepteurs avec un système de détection d'imagerie par résonance des plasmons de surface nous a permis de réaliser une langue électronique capable de différencier des échantillons de différentes complexités, y compris des protéines pures et des mélanges complexes. Cela se fait grâce aux profils et images d'évolution continue, assimilés à des « empreintes digitales » des échantillons. D'un autre côté, ce système peut être utilisé en tant qu'outil pour la conception de surfaces biomimétiques 2D et 3D. Ce système est prometteur pour l'étude des interactions sucre-protéine et pour la préparation de nanovecteurs biomimétiques qui ciblent de façon spécifique des protéines d'intérêt. / L'objectif de cette thèse est le développement d'une langue électronique avec une méthode simplifiée d'obtention de récepteurs à réactivité croisée. Ces récepteurs sont préparés par une approche combinatoire novatrice qui consiste au mélange et à l'auto-assemblage de deux disaccharides. Le couplage de ces récepteurs avec un système de détection d'imagerie par résonance des plasmons de surface nous a permis de réaliser une langue électronique capable de différencier des échantillons de différentes complexités, y compris des protéines pures et des mélanges complexes. Cela se fait grâce aux profils et images d'évolution continue, assimilés à des « empreintes digitales » des échantillons. D'un autre côté, ce système peut être utilisé en tant qu'outil pour la conception de surfaces biomimétiques 2D et 3D. Ce système est prometteur pour l'étude des interactions sucre-protéine et pour la préparation de nanovecteurs biomimétiques qui ciblent de façon spécifique des protéines d'intérêt.

No description available.

Os receptores dos hormônios da tireóide (TRs) são fatores de transcrição envolvidos na diferenciação celular, metabolismo e funções fisiológicas da maioria dos tecidos. Muitos estudos mostram que diversos efeitos farmacológicos mediados pelos TRs podem ser benéficos na farmacoterapia, especialmente aqueles mediados pelo TR que podem ser úteis em condições médicas importantes como obesidade, hipercolesterolemia e diabetes. Além disso, a descoberta que o TR é a isoforma predominante no coração, mediando a maioria dos efeitos cardiovasculares prejudiciais, estimulou a pesquisa por ligantes seletivos para o TR que poderiam ser utilizados em quadros clínicos importantes com perfil de segurança aceitável. Foi realizado um estudo das relações quantitativas entre a estrutura e atividade (QSAR) de um conjunto de compostos com atividade biológica descrita para TR e TR, que gerou modelos de Holograma QSAR com elevada consistência interna e externa, apresentando bom poder de correlação e predição das propriedades biológicas. Também foi realizado um minucioso estudo de triagem virtual, que propiciou a seleção de 7 compostos que foram adquiridos para terem suas atividades biológicas avaliadas. Ensaios de transfecção e gene repórter foram estabelecidos e utilizados na avaliação da atividade biológica dos compostos selecionados pelo ensaio virtual. Finalmente, um ensaio utilizando ressonância plasmônica de superfície (SPR) foi desenvolvido e utilizado para avaliar a atividade agonista desses compostos, e que pode ser útil para avaliar a atividade de novos ligantes. A técnica de SPR também foi empregada em um cuidadoso estudo da interação do TR com seus correguladores, que incluiu estudos cinéticos e termodinâmicos, propiciando a determinação das taxas cinéticas e parâmetros termodinâmicos para a interação do complexo TR-T3 com peptídeos derivados de dois de seus correguladores. Os resultados obtidos são relevantes e devem ser considerados no planejamento de futuros experimentos utilizando o LBD de TR e agonistas. / The thyroid hormone receptors (TRs) are transcriptional factors involved in cell differentiation, development, metabolism and physiological function of most tissues. Many lines of evidence show that several pharmacological actions of TRs might be beneficial in medical therapy, specially those mediated by TR that target important medical conditions like obesity, hypercholesterolemia and diabetes. Additionally, the findings that TR is the predominant isoform in the heart and mediates most of the TRs deleterious cardiovascular effects, stimulated the research for selective TR ligands which could address important medical needs with an acceptable safety profile. In this PhD thesis, studies of the quantitative structure-activity relationships (QSAR) of a dataset of compounds with reported biologic activity for both TR and TR were performed, and statistically significant Hologram QSAR models with good predictive ability for untested compounds were created. In parallel, a careful virtual screening procedure was executed, leading to the selection of 7 compounds which were purchased for the evaluation of their biological activities. Cell transfection and reporter gene assays were developed, validated and used to evaluate the biological activities of these compounds. Finally, a surface plasmon resonance (SPR) assay was developed and used to assess the agonistic activity of these compounds. The SPR technique was also employed in a careful study of the interaction between the ligand binding domain of TR and peptides derived from its coregulators, which included the determination of the kinetic and thermodynamic parameters for this interaction. The results suggest that flexibility plays an important role in the interaction between the receptor and its coregulators, and point out important aspects of experimental design that should be addressed when using TR LBD and its agonists. Furthermore, the methodology described here may be useful for the identification of new TR ligands.