Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the cell bodies of FUS ALS patients motor neurons. The nature of these inclusions has remained elusive, as the proteins localized to them have not been identified. Additionally, the functional consequence of the accumulation of cytoplasmic FUS inclusions has not been established, nor is it understood how they contribute to selective motor neuron death. We carried out two related, but independent studies to characterize the proteins that may be included in FUS-positive inclusions. In this first study, we utilized immunoprecipitation of wild-type and mutant FUS in the presence and absence of RNase, followed by LC MS/MS. The identified proteins represent those that directly or indirectly interact with FUS, with relatively high affinity that can be pulled down with immunoprecipitation. A wide variety of interacting proteins were identified and they are involved in a multitude of pathways including: chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. Their interaction with FUS varied greatly in their requirements for RNA. Most notably, FUS interacted with hnRNPA1 and Matrin-3, proteins also known to cause familial ALS. Immunofluorescent staining of proteins interacting with mutant FUS were localized to cytoplasmic inclusions. We concluded that mis-localization of these proteins potentially lead to their dysregulation or loss of function, thus contributing to FUS pathogenesis. In the second study, we developed a protocol to isolate dynamic FUS inclusions and employed LC MS/MS to identify all proteins associated with FUS inclusions. We identified a cohort of proteins involved in translation, splicing, and RNA export to be associated with the FUS inclusions. Further pathway and disease association analysis suggested that proteins associated with translation and RNA quality control pathways may be the most significant. Protein translation assays using both N2A and ALS patient fibroblasts demonstrated suppression of protein biosynthesis in mutant FUS expressing cells. However, translation initiation was not impaired. To understand how protein synthesis is suppressed by mutant FUS mediated defects in RNA metabolism, we examined changes in a well conserved RNA turnover pathway namely: nonsense mediated decay (NMD). We found that NMD is hyperactivated in cells expressing mutant FUS, likely due to chronic suppression of protein translation shifting the pathways autoregulatory circuit to allow for hyperactivation. We concluded that mutant FUS suppresses protein biosynthesis and disrupts NMD regulation. These defects together likely contribute to motor neuron death.

ABB Corporate Research was looking to redevelop one product to be manufactured via polymer additive manufacturing (AM), as opposed to its previously traditionally manufacturing method. The current product is cylindrical in shape and must withstand a certain amount of hydrostatic pressure. Due to the pressure and the current design, the cannister is prone to buckling failure. The cannister is currently produced from two cylindrical tube parts and two spherical end sections produced from solid blocks of the same material. For assembly, an inner assembly is inserted into one of the tube parts and then all parts are welded together. This product is also custom dimensioned for each purchase order. The purpose of investigating this redevelopment for AM is to analyse if an updated inner design unique to additive manufacturing is able to increase the performance of the product by increasing the pressure it can withstand from both a material failure standpoint and a buckling failure. The redevelopment also aims to see if the component count and process count can be decreased. Ultimately, two product solutions are suggested, one for low pressure ranges constructed in ABS and one for high pressure ranges constructed in Ultem 1010. To accomplish this, relevant literature was referred to gain insight into how to reinforce cylindrical shell structures against buckling. Design aspects unique to AM were also explored. Iterations of these two areas were designed and analysed, which led to a final design choice being decided upon. The final design is ultimately based on the theory of strengthening cylindrical structures against buckling through the use of ring stiffeners while also incorporating AM unique design aspects in the form of hollow network structures. By utilizing finite element analysis, the design was further developed until it held the pressure required. Simulation results suggest that the ABS product can withstand 3 times higher pressure than the original design while being protected against failure due to buckling. The Ultem simulation results suggest that the product can withstand 12 times higher pressure than the current design while also being protected against failure due to buckling. Part count and manufacturing processes are also found to have decreased by half. Post-processing treatments were also explored, such as the performance of sealants under pressure and the effects of sealants on material mechanical properties. Results show that one sealant in particular, an acrylic spray, is most suitable to sealing the ABS product. It withstood a pressure of 8 bar during tests. The flexural tests showed that the sealant did indeed increase certain mechanical properties, the yield strength, however did not affect the flexural modulus significantly. This work gives a clear indication that the performance of this product is feasibly increased significantly from redeveloping it specifically to AM.

Les tanins condensés sont largement répandus et très abondants dans la nature. Au cours des dernières décennies, ces tanins ont été abondamment utilisés pour la production de formulations thermodurcissables (par exemple, les adhésifs pour le collage du bois, les matériaux en mousse) en raison de leur réactivité chimique. Cependant, ils présentent également un grand potentiel en tant que composants pour la conception de matériaux polymères innovants en raison de leurs propriétés physico-chimiques (p. ex. antioxydantes, antimicrobiennes et stabilisantes). Afin d’étendre les domaines d’utilisation des tanins aux matériaux polymères, le principal verrou scientifique et technique réside dans leur incompatibilité avec les polymères hydrophobes. À cette fin, trois voies de modification ont été mises au point pour améliorer la compatibilité des tanins avec les matrices PP ou PLA. Dans la première partie, les PP/ tanins ont été modifiés avec du glyoxal par vulcanisation dynamique. Après extrusion réactive, les tanins vulcanisés présentent une meilleure compatibilité avec la matrice PP et des propriétés anti-UV. La deuxième approche consiste en une modification par estérification à l'aide d'anhydride acétique. Avec cette méthode, des teneurs élevées en AT ont pu être incorporées au PLA, jusqu'à 30 % en poids et jusqu'à 20 % sans diminution notable des propriétés mécaniques ni impact sur la morphologie de surface. Ces composites PLA/AT sont imprimables en impression 3D par dépôt de matière fondue. Dans la troisième partie, une compatibilisation réactive a été réalisée avec succès pour améliorer l'adhésion interfaciale entre PLA et les tanins condensés en utilisant du 3-aminopropytriéthoxysilane, du diisocyanate de méthylène diphényle et du peroxyde de dicumyle (DCP). / Condensed tannins are widely distributed and highly abundant in nature. In the past decades, such tannins have played an important role in thermosetting systems (e.g. adhesives for wood bonding, foam material) because of their chemical reactivity. However, they also exhibit great potential as a component of polymeric materials because of their physicochemical properties (e.g. antioxidant, antimicrobial and stabilizing properties), which are promising for material preparation. In order to transform tannins from traditional application to a broaden application in polymeric materials, the main challenge facing tannins are their incompatibility with hydrophobic polymer. For this purpose, three modification pathways were developed to improve the compatibility of tannins with PP or PLA matrix. In the first part, PP/ tannins were modified with hexamine or glyoxal via dynamic vulcanization technique. After vulcanized extrusion, vulcanized tannins present better compatibility and UV protective performance in PP matrix. The second approach is CTs modified with acetic anhydride. With this method, up to 30 wt% acetylated tannin (AT) can be well incorporated with PLA while PLA containing up to 20 wt% AT did not deteriorate the mechanical property and surface morphology. This PLA/AT composites are printable via fused deposition modeling process. In the third part, the efficient reactive compatibilization have been successful used to improve the interfacial adhesion between PLA and CTs by using 3-aminopropytriethoxysilane, methylene diphenyl diisocyanate, and dicumyl peroxide (DCP).

A class of linear diamidines was synthesized for the evaluation as a treatment of Human African Trypanosomiasis. These fused heterocyclic compounds are thiazole[5,4-d]thiazoles and are of interest because the parent compound, 2,5-Bis(4-amidinophenyl)-thiazolo[5,4-d]thiazole HCl salt, which is also called DB 1929, has exhibited a low nanomolar IC50 value against Trypanosoma brucei rhodesiense and has shown selectivity for binding to the human telomere G-quadruplex over that of DNA duplex. A fluoro and a methoxy derivative have been synthesized and are currently undergoing testing for activity and binding affinity. In addition, fluorescence studies of selected diamidines were done to study the effect of structural variation on fluorescence. This data is useful since it can determine what types of moieties are needed to yield a compound that will fluoresce in the higher wavelengths (500 nm and above) of the visible spectrum, which would be advantageous in determining the uptake of the drug in the trypanosome within the endemic areas of Africa with a simple microscope.

The structural, electronic, and optical properties of a series of organic pi-conjugated polymer, oligomer, or molecular materials of interest for applications in organic electronics are described. For this purpose, quantum-chemical techniques ranging from Density Functional Theory to Hartree-Fock ab initio and semiempirical methods are used to evaluate the charge-transport, charge-transfer, and electroluminescence properties of pi-conjugated organic materials. First, the effect of electronic polarization on the charge-transport parameters of organic semiconductors is discussed. A generalized methodology based on a basis set orthogonalization procedure is developed to determine reliable charge-transport characteristics. The charge-transport parameters of a number of organic semiconductors such as oligoacenes and derivatives are studied with this methodology. Then, triplet emitters, in particular iridium complexes, that achieve high efficiency electroluminescence in organic light-emitting diodes are discussed. The effects of ligand substitution and orientation on the luminescent properties of iridium compounds are investigated in order to develop structure-properties relationships. The emission properties of these complexes are found to be governed by an interplay between metal-to-ligand charge transfer excitations and ligand-centered and/or interligand excitations. The extent of mixing of these various excitations turns out to be highly dependent on the nature of the substituents. Design strategies to shift the emission color towards deep blue are proposed. Finally, several classes of materials acting as hosts for phosphorescent emitters are studied. It is shown that restricting the conjugation length leads to high energy gap host materials suitable for blue phosphorescent emitters.

Darbe pristatomi eksperimentiniai bei teoriniai rezultatai, susiję su skaidriųjų terpių lūžio rodiklio pokyčio indukavimu. Parodoma, kad lydytą kvarcą veikiant Yb:KGV lazerine sistema generuojamais impulsais, jame galima sukurti modifikuoto lūžio rodiklio sritis. Šios sritys pasižymi dvejopu šviesos lūžimu, atsirandančiu dėl medžiagos tūryje besiformuojančių nanogardelių, o modifikuotų sričių vienalytiškumas priklauso nuo akumuliacinių efektų. Pakitusio lūžio rodiklio sritis taip pat galima formuoti ir ličio niobato kristale. Priklausomai nuo spinduliuotės parametrų, šiame kristale galima įrašyti stabilius modifikuoto lūžio rodiklio darinius, o taip pat ir nestabilias modifikacijas, atsirandančias dėl fotorefrakcinio reiškinio. Pastarąjį efektą galima panaudoti daugkartiniam informacijos įrašymui. Pademonstruoti efektyvūs fotoniniai elementai, tūrinės Brego gardelės, įrašytos tiek lydyto kvarco, tiek ličio niobato kristalo tūryje. Pateikiama metodika, skirta lazerio indukuoto lūžio rodiklio pokyčiui nustatyti matuojant Brego gardelių difrakcinius efektyvumus. Taip pat tyrinėjama kaip modifikuoti dariniai lemia superkontinuumo ir šviesos gijos formavimosi reiškinius lydytame kvarce. / The study on refractive index modification of transparent materials with ultrashort laser pulses is presented in this dissertation. Based on experimental data it was demonstrated, that using ultrashort pulses, generated with Yb:KGW laser system, it is possible to produce modified refractive index zones in the fused silica glass, that possess birefringence. This effect is caused by nanogratings that form in the bulk of the material. Homogeneity of the modified zones is determined by the accumulation effects, mainly the number of pulses that affect each area. Refractive index variations can be created also in crystalline material such as lithium niobate. Depending on the writing pulse parameters different types of modifications can be created: permanent modification that is caused by crystal amorphization and non-stable modifications that originate from the photorefractive properties of the crystal. Latter modifications can be used for three-dimensional, rewritable data recording. Highly efficient photonic elements, such as volume Bragg gratings, recorded in fused silica and lithium niobate crystal are demonstrated. The technique allowing the evaluation of refractive index change applying Bragg gratings is described. Also modification influence on nonlinear processes that appear in fused silica such as filament formation and supercontinuum generation is experimentally investigated.

The study on refractive index modification of transparent materials with ultrashort laser pulses is presented in this work. Based on experimental data it was demonstrated, that using ultrashort pulses, generated with Yb:KGW laser system, it is possible to produce modified refractive index zones in the fused silica glass, that possess birefringence. This effect is caused by nanogratings that form in the bulk of the material. Homogeneity of the modified zones is determined by the accumulation effects, mainly the number of pulses that affect each area. Refractive index variations can be created also in crystalline material such as lithium niobate. Depending on the writing pulse parameters different types of modifications can be created: permanent modification that is caused by crystal amorphization and non-stable modifications that originate from the photorefractive properties of the crystal. Latter modifications can be used for three-dimensional, rewritable data recording. Highly efficient photonic elements, such as volume Bragg gratings, recorded in fused silica and lithium niobate crystal are demonstrated. The technique, allowing the evaluation of refractive index change applying Bragg gratings, is described. Also modification influence on nonlinear processes that appear in fused silica such as filament formation and supercontinuum generation is experimentally investigated. / Darbe pristatomi eksperimentiniai bei teoriniai rezultatai, susiję su skaidriųjų terpių lūžio rodiklio pokyčio indukavimu. Parodoma, kad lydytą kvarcą veikiant Yb:KGV lazerine sistema generuojamais impulsais, jame galima sukurti modifikuoto lūžio rodiklio sritis. Šios sritys pasižymi dvejopu šviesos lūžimu, atsirandančiu dėl medžiagos tūryje besiformuojančių nanogardelių, o modifikuotų sričių vienalytiškumas priklauso nuo akumuliacinių efektų. Pakitusio lūžio rodiklio sritis taip pat galima formuoti ir ličio niobato kristale. Priklausomai nuo spinduliuotės parametrų, šiame kristale galima įrašyti stabilius modifikuoto lūžio rodiklio darinius, o taip pat ir nestabilias modifikacijas, atsirandančias dėl fotorefrakcinio reiškinio. Pastarąjį efektą galima panaudoti daugkartiniam informacijos įrašymui. Pademonstruoti efektyvūs fotoniniai elementai, tūrinės Brego gardelės, įrašytos tiek lydyto kvarco, tiek ličio niobato kristalo tūryje. Pateikiama metodika, skirta lazerio indukuoto lūžio rodiklio pokyčiui nustatyti matuojant Brego gardelių difrakcinius efektyvumus. Taip pat tyrinėjama kaip modifikuoti dariniai lemia superkontinuumo ir šviesos gijos formavimosi reiškinius lydytame kvarce.

No description available.

Cette thèse porte sur l’amélioration de la résistance au flux laser de la surface descomposants optiques en silice en régime nanoseconde. Ce matériau est utilisé sur lesinstallations de laser de puissance telles que le Laser Mégajoule. Pour augmenter la durée de viedes composants optiques et garantir le fonctionnement nominal de cette installation,l’endommagement laser doit être maîtrisé. Il s’agit d’une dégradation irréversible de la surfacedes composants causée par l’interaction entre le faisceau laser et des défauts précurseurs. Cesderniers sont une conséquence de la synthèse de la silice puis du polissage des composants etleur présence peut être limitée par une action de traitement chimique réalisée à l’issue dupolissage qui consiste à éroder la surface de silice à l’aide d’une solution chimique. Cette érosionne doit cependant pas dégrader la qualité de la surface polie et ses propriétés optiques. Cettethèse se concentre sur la réalisation de cette étape de traitement chimique et se décompose entrois études. La première porte sur la caractérisation de la pollution induite en surface par lepolissage et sa suppression par le traitement chimique. La seconde et la troisième analysentl’impact des traitements chimiques respectivement sur les propriétés optiques de la surface etsur les rayures de polissage. Ces études nous permettent d’évaluer l’influence des différentsparamètres du traitement chimique, tels que la solution, le système de mise en oeuvre etl’épaisseur érodée, sur les performances apportées aux composants optiques. Finalement,l’ensemble de ces connaissances nous conduit à proposer un traitement chimique optimisé quiaméliore la tenue au flux des composants optiques sans dégrader leurs propriétés optiques. / In this thesis, laser-induced damage resistance improvement of fused silica opticsis investigated in the nanosecond regime. This material is used on high power laser facilitiessuch as the Laser Mégajoule. In order to improve the optics life time and to ensure the nominaloperation of this facility, laser induced damage has to be controlled. This phenomenon is anirreversible modification of the components surface because of the interaction between the laserbeam and precursors defects. These defects are a consequence of the synthesis of silica and thepolishing of the optics and their presence can be reduced by a wet etching. This process consistsin an erosion of the surface using a chemical solution however optical properties must remainunchanged. In this thesis, we focus on the wet etching process and we conduct three studies. Thefirst one is about the characterization of the polishing induced contamination and the capabilityof a wet etching to remove it from the surface. The second and the third analyzes are about theimpact of the wet etching respectively on the surface and on the scratches. These studies allowus to evaluate the influence of the wet etching parameters as the chemical solution, the systemused and the deep etched. Finally, the highlights obtained thanks to these studies enable tooptimize the wet etching process and improve the laser induced damage resistance ofcomponents without compromising their optical properties.

Additive manufacturing is gaining popularity at a rapid rate and has been a resourceful production process to reduce material usage, wastage (scrap) and manufacturing costs for various applications. The project conducted, emphasizes on Thermoplastic Elastomer (TPE SE6300C-65A) material, which is a highly versatile compound, and has the ability to exhibit properties of both rubber (Elastomers) in terms of flexibility and plastic (Polymers) in terms of recyclability. Cost reduction without compromising quality is one of the important factors for industries. The project involves the use of TPE pellets to extrude filaments that could be used for 3D Printing. Filament extrusion involves process variables like Nozzle Temperature, De-humidification of pellets, Diameter of the nozzle, Distance of collection, Cooling and Angle of inclination of the extruder. These process variables are optimized to accomplish the desired quality of filament. The filament produced through extrusion is further used to make products using Fused Deposition Modeling (FDM). FDM also involves numerous process variables like Layer Thickness, Build Orientation, Print Infill, Print Speed etc. In this study, different test specimens, in terms of geometrical shapes are printed from the material, TPE SE6300C-65A and tested in order to understand how the surface features as well as the dimensional accuracy change with different process variables. It is observed that the surface topography produced throughout FDM process is majorly affected by the angle of orientation of the printed part. The main goal of this thesis is to give the reader a better understanding on which process variable, such as layer thickness, temperature and print speed affect the surface roughness of the models and also a comparison between these three variables, highlighting which is more or less affecting. It is also observed the dimensional accuracy of the real specimen deviate from the value input into the CAD software. The results obtained in this study clearly suggest that there is a lot of opportunities for future improvements especially regarding the dimensional accuracy, it is imperative to achieve the highest precision possible in order to have commercial values for the FDM 3D printing.