As pregas vocais (PV) são estruturas únicas, altamente especializadas na vibração para a produção sonora. Em grande parte, decorrente da estruturação em camadas da lâmina própria (LP). Essa estruturação não está presente ao nascimento, somente após anos de uso vibratório e fonatório da PV é que a LP está finalmente estruturada. As pregas ventriculares (PVT) não são, habitualmente, estruturas vibratórias na produção sonora, e possuem a LP menos organizada em estratos, sendo menos especializadas para a vibração. Até o presente momento, não se tem conhecimento do que ocorre com os constituintes da LP de PVTs de pessoas que as utilizam como fonte produtora de voz. No presente estudo, foram comparados os constituintes colágenos e as fibras elásticas da LP de PVTs de indivíduos que as utilizam como principal fonte vibratória na produção de voz com o grupo controle. Foram selecionados seis indivíduos que utilizavam pelo menos uma das PVTs como fonte de vibração para a produção sonora por ao menos seis anos. Delas, colheu-se pequeno fragmento (0,5 cm2), que após processamento histológico, as fibras colágenas foram coradas com Picrosirus Red e as fibras elásticas com Weigert resorcina-fucsina. Foram obtidas 54 imagens da camada mais superficial da LP de cada PVT para cada coloração. Após a aquisição das imagens, as fibras colágenas tipo I e tipo III, colágenas totais e fibras elásticas foram quantificadas utilizando-se o software Image-Pro Plus, e comparadas com as PVTs dos controles. A análise estatística foi realizada por meio do teste T de Student para amostras não pareadas. A porcentagem de colágeno total na camada mais superficial da LP de PVT utilizada como fonte vibratória para a produção de som foi significativamente maior em relação aos controles. O mesmo ocorreu com a quantidade de colágeno tipo I. Não houve diferenças na quantidade de colágeno tipo III e de fibras elásticas. Como conclusão, pode-se afirmar que a utilização da PVT como fonte vibratória produtora de som leva ao aumento da quantidade de fibras colágenas totais e do tipo I na camada mais superficial da sua LP / The vocal folds (VF) are unique structures, highly specialized in vibrating for sound production. This specialization is mainly due to a layered structure of the lamina propria (LP). This layered structure is not present at birth, and develops only after a several years of phonation. The LP of the mature vocal fold consists of three layers. The ventricular folds (VTF) are not originally vibrating structures for sound production, and in its LP the layers are poorly organized. It is not known what happens to the constituents of the LP in the VTF in subjects that use VTF vibration as a source of voice production. In the present study, the distribution and quantity of collagen and elastic fibers of the lamina propria from VTF of patients that use it as the main source of vibration for voice production were compared with the VTF from control subjects. Six individuals that used at least one of the VTF as source of vibration for sound production for minimum of six years were selected. A small fragment of VTF (0.5 cm2) used as vibration source of sound production was collected from each subject. The samples were processed for histological analysis. Collagen fibers were stained with Picrosirus Red and elastic fibers were stained with Weigert\'s Resorcin-Fuchsin. A total of 54 images were obtained from the superficial layer of the LP from each VTF for each stain. After image acquisition, collagen type I, III, total collagen and elastic fibers were quantified and compared with the VTF from the control group. Quantification was done using Image-Pro Plus software. Statistics were performed using an unpaired Student T test. The amount of total collagen in the most superficial layer of LP when the VTF was used as the source of vibration for the production of sound was significantly higher when compared to controls. The same result was seen for the amount of type I collagen in both groups. There was no difference in the quantity of type III collagen and elastic fibers between the two groups. Vibration of the VTF as a source of sound, for at least six years, leads to an increase in the amount of total collagen fibers and an increase in type I collagen, but does not increase the amount of type III collagen and elastic fibers in the most superficial layer of LP. These results may help elucidate the unique development of the lamina propria of the vocal fold

A novel approach is proposed for modeling of structurally variable regions in proteins. In this approach, a prerequisite sequence-structure alignment is examined for regions where the target sequence is not covered by the structural template. These regions, extended with a number of residues from adjacent stem regions, are submitted to fold recognition. The alignments produced by fold recognition are integrated into the initial alignment to create a multiple alignment where gaps in the main structural template are covered by local structural templates. This multiple alignment is used to create a protein model by existing protein modeling techniques. Several alternative parameters are evaluated using a set of ten proteins. One set of parameters is selected and evaluated using another set of 31 proteins. The most promising result is for loop regions not located at the C- or N-terminal of a protein, where the method produces an average RMSD 12% lower than the loop modeling provided with the program MODELLER. This improvement is shown to be statistically significant.

Lors de ce travail de thèse nous nous sommes intéressés à deux thèmes principaux dans le but de fabriquer des matériaux conducteurs chiraux : la synthèse de TTF-hélicènes présentant une chiralité hélicoïdale moléculaire, ainsi que l’obtention de molécules de symétrie 3 à base de TTF ayant la capacité à former des auto-assemblages supramoléculaires hélicoïdaux. Dans la partie TTF-hélicène, plusieurs tailles d’hélicènes ont été envisagées avec pour objectif d’obtenir des énantiomères stables et séparables. Ils ont été caractérisés par diffraction de rayons X, de même que les sels obtenus par électrocristallisation. De plus, une étude théorique de la réaction de photocyclisation des stilbènes en hélicènes a été menée pour comprendre sa régiosélectivité. Les molécules de symétrie 3 sont composées d’un coeur BTA-DABP sur lequel sont fixés des TTF avec leurs substituants chiraux. L’assemblage colonnaire des molécules est étudié par CD et les fibres formées sont observées par microscopie ce qui permet de déterminer leur hélicité. On varie le cœur ainsi que les groupements fixés dessus. / In this work, we have been interested in two different topics to make chiral conducting materials: the synthesis of TTF-helicenes, with molecular helical chirality, as well as the formation of three-fold symmetry molecules based on TTF units able to self-assemble into supramolecular helical aggregates. For the TTF-helicenes, several lengths of helicenes are considered in order to form stable and separable enantiomers. They are characterized by X-ray diffraction just as the salts that are obtained by electrocrystallization. Moreover, a theoretical study of the photocyclisation reaction of stilbenes into helicenes was performed to understand its regioselectivity. The three-fold symmetry molecules are composed of a BTA-DABP core on which TTF with chiral substituents are fixed. The assembly into columnar aggregates is followed by CD and the fibers formed are observed by microscopy in order to determine their helicity. Variation of the core and the substituents are made.

Microarray platforms have been around for many years and while there is a rise of new technologies in laboratories, microarrays are still prevalent. When it comes to the analysis of microarray data to identify differentially expressed (DE) genes, many methods have been proposed and modified for improvement. However, the most popular methods such as Significance Analysis of Microarrays (SAM), samroc, fold change, and rank product are far from perfect. When it comes down to choosing which method is most powerful, it comes down to the characteristics of the sample and distribution of the gene expressions. The most practiced method is usually SAM or samroc but when the data tends to be skewed, the power of these methods decrease. With the concept that the median becomes a better measure of central tendency than the mean when the data is skewed, the tests statistics of the SAM and fold change methods are modified in this thesis. This study shows that the median modified fold change method improves the power for many cases when identifying DE genes if the data follows a lognormal distribution.

The High Arctic has been a complex region of collisional and extensional tectonism through the Mesozoic and Cenozoic. Svalbard, the sub-aerial exposure of the northwestern Barents Shelf, is an excellent natural laboratory investigating for High Arctic tectonism. Using apatite and zircon (U-Th)/He low-temperature thermochronometry combined with geological constraints, we resolve Cretaceous through Paleogene time-temperature histories for four regions of the Southwestern Province. Our results indicate a temperature gradient from south to north of ~185°C to >200°C, respectively, as a consequence of sedimentary burial and elevated geothermal gradient ( 45°C/km) from High Arctic Large Igneous Province activity. Late Cretaceous cooling affected all regions during regional exhumation related to initial rifting in the Eurasian Basin. During Eurekan tectonism: 1) our models indicate a heating event (55-47 Ma) characterized by overthrusting and a lack of erosion of the West Spitsbergen Fold-and-Thrust Belt, with Central Basin sediments derived from northern Greenland, followed by 2) a subsequent cooling event (47-34 Ma) corresponding to a shift in tectonic regime from compression to dextral strike-slip kinematics; exhumation of the WSFTB coincided with strikeslip tectonics.

3D geological modelling is becoming an effective tool for communication and development of geological understanding. This is due to increased computer performance and availability of improved geological modelling software. 3D geological modelling technology has reached the stage where it can be implemented in regionally extensive and geologically complex settings, with the ability to achieve geological insight beyond what could otherwise have been gained through 2D investigations alone. Insight includes better constrained fault and horizon topologies, refined fold geometries, improved understanding of tectonic processes, and characterization of deformational events. By integrating field observations, aeromagnetic maps, and 3D modelling techniques in the northern Labrador Trough, a regionally extensive and structurally complex geological environment, regional faults geometries and topological relationships were refined. Additionally, a new fault, the Ujaralialuk Fault, and two shear zones were interpreted. During modelling, several challenges were identified, including higher computational costs for regionally extensive models, sparse 3D constraints, algorithmic limitations related to complex geometries, and the large investment of time and effort required to produce a single model solution. A benefit of this investigation is that new insight was also gained for a greenfields region which may assist future exploration efforts. Developing 3D models in challenging environments allows for better definition of future workflow requirements, algorithm enhancements, and knowledge integration. These are needed to achieve a geologically reasonable modelling standard and gain insight for poorly constrained geological settings.

High Voltage (HV) cables are designed to transmit electrical power from the source to the placewhere it is consumed. The global trend towards renewable energy sources e.g. wind farms, hy-droelectric and solar panels have led to an increase in the use of HV cables, as these sources aresituated in remote locations far from the areas where they are consumed. Therefore. there is aneed for developing efficient power transmission cables.Mass-impregnated (MI) cable is a type of HV cable which contains an electrical insulation layerof oil or mass impregnated cellulose paper. Due to its excellent dielectric properties, MI cableshas been established as a solution for high voltage electrical transmission system, which has beenused for several decades.The main area of interest in this thesis is the paper insulation in the MI cable. It is importantto ensure that the paper insulation structure is robust enough to avoid any formation of damageand/or defects due to excessive deformations during cable production, handling and installation,which might affect the overall electrical performance of the cable. During handling, the drylapped cable needs to be bent and unbent several times and there is a risk that the insulationwill develop voids due to structural defects, thereby reducing the dielectric capacity of the cable.An example of typical structural defects in MI cables is, so-called, diamond folds, i.e. a collec-tive buckling of several paper strips due to axial compressive load resembling a diamond shapedpattern.The goal of this thesis work is to contribute to the knowledge of the mechanism of diamond foldsin MI cable; the onset of diamond fold and post-buckling responses. The contributions from thecable design or production parameters are also studied. The analyses will be conducted usingnumerical simulation techniques and will be compared to results from characterization tests al-ready conducted in mechanics lab at NKT Technology consulting.The results of this thesis has given an insight about the effect of insulation design parameterssuch as registration, butt-gaps, coefficient of friction and number of layers, on the diamond foldbuckling behavior in an MI cable insulation. It is recommended that these parameters have tobe carefully controlled so as to avoid formation of diamond fold buckling in the insulation.

Doctor Scientiae / An esterase and lipase producing Burkholderia multivorans strain was isolated by culture enrichment strategies. A shotgun library of Burkholderia multivorans genomic DNA (prepared in E. coli/pUC18) was screened for lipase and esterase activities. Three positive recombinant clones, pTEND5, pHOLA6 and pRASHI4, conferring esterolytic and lipolytic phenotypes respectively, were identified. Full-length sequencing of DNA inserts was performed using subeloning and "primer-walking" strategies. Nucleotide sequence analysis revealed that the pRASH14 plasmid DNA consisted of two open reading frames (ORPI and ORP2) encoding 356 and 350 amino acids, respectively. Database searches revealed that ORPI and ORP2 were homologous to lipases and chaperones from subfamily I.2. In the pTEND5 sequence, an open reading frame consisting of 978 bp, encoding 326 amino acids, was identified. Database searches revealed that this open reading frame was homologous to family Vesterases. Nucleotide sequence analysis revealed that pHOLA6, plasmid DNA consisted of 1194 bp encoding 398 amino acids and showed homology to family VIII esterases. The primary structures of LipA, EstEFH5 and EstBL from pRASHI4, pTEND5 and pHOLA6, respectively, showed a classical GxSxG motif, which is conserved in many serine hydrolases. In addition, EstBL also showed a consensus SxxK motif, the serine of which acts as a catalytic nucleophile in class C B-lactames and some peptidases.

Developing lifelike vocal fold models is challenging due to various associatedbiomechanical complexities. Nevertheless, the development and analysis of improved vocal foldmodels is worthwhile since they are valuable tools for gaining insight into human vocal foldvibratory, aerodynamic, and acoustic response characteristics. This thesis seeks to contribute tothe development of computational and physical vocal fold modeling in two ways. First is byintroducing a method of obtaining internal deformation fields within vibrating synthetic vocal foldmodels; second is by presenting an optimization algorithm coupled with a computational vocalfold model to optimize geometry and stiffness of a synthetic vocal fold model to achieve morerealistic vibration patterns.The method for tracking the internal deformation of self-oscillating vocal fold models isbased on MR imaging. Silicone models scaled to four times life-size to lower the flow-inducedvibration frequency were imbedded with fiducial markers in a coronal plane. Candidate markermaterials were tested using static specimens, and two materials, cupric sulfate and glass, werechosen for testing in the vibrating VF models. The vibrating models were imaged using a gatedMRI protocol wherein MRI acquisition was triggered using the subglottal pressure signal. Twodimensionalimage slices at different phases during self-oscillation were captured, and in eachphase the fiducial markers were clearly visible. The process was also demonstrated using a threedimensionalscan at two phases. The benefit of averaging to increase signal-to-noise ratio wasexplored. The results demonstrate the ability to use MRI to acquire quantitative deformation datathat could be used, for example, to validate computational models of flow-induced VF vibrationand quantify deformation fields encountered by cells in bioreactor studies.A low fidelity, two-dimensional, finite element model of VF flow-induced vibration wascoupled with a custom MATLAB-based genetic algorithm optimizer. The objective was to achievea closed quotient within the normal human physiological range. The results showed that changesin geometry and stiffness would lead to a model that exhibited the desired characteristics. Aphysical model based on optimized parameters was then fabricated and the closed quotient wastested. The physical model successfully vibrated with nonzero closed quotient as predicted by thecomputational model.

Applying the anisotropy of magnetic susceptibility to analogue models provides detailed insights into the strain distribution and quantification of deformation within contractional tectonic settings like fold-and-thrust belts (FTBs). Shortening in FTBs is accommodated by layer-parallel shortening, folding, and thrusting. The models in this research reflect the different deformation processes and the resulting magnetic fabric can be attributed to thrusting, folding and layer-parallel shortening. Thrusting develops a magnetic foliation parallel to the thrust surface, whereas folding and penetrative strain develop a magnetic lineation perpendicular to the shorting direction but parallel to the bedding. These fabric types can be observed in the first model of this study, which simulated a FTB shortened above two adjacent décollements with different frictional properties. The different friction coefficients along the décollements have not only an effect on the geometric and kinematic evolution of a FTB, but also on the strain distribution and magnitude of strain within the belt.  The second series of models performed in this study show the development of a thrust imbricate and the strain distribution across a single imbricate in more detail. Three models, with similar setup but different magnitudes of bulk shortening, show strain gradients by gradual changes in principal axes orientations and decrease in degree of anisotropy with decreasing distance to thrusts and kinkzones. These models show that at the beginning of shortening, strain is accommodated mainly by penetrative strain. With further shortening, formation of thrusts and kinkzones overprint the magnetic fabric locally and the degree of anisotropy is decreasing within the deformation zones. At thrusts, an overprint of the magnetic fabric prior deformation towards a magnetic foliation parallel to the thrust surfaces can be observed. A rather complex interplay between thrusting and folding can be analysed in the kinkzones. In general, this thesis outlines the characteristics of magnetic fabric observed in FTBs, relates different types of magnetic fabric to different processes of deformation and provides insights into the strain distribution of FTBs.