Dissertations / Theses on the topic 'Matrice G'

La rapidité du changement climatique observé et prédit soulève la question de la vitesse à laquelle les espèces pourront s'adapter au climat futur. Les populations exposées aux changements de conditions environnementales peuvent s'adapter sur place (sans migration) grâce, dans un premier temps, à la réponse plastique des individus, puis, à long terme, par la réponse à la sélection (adaptation génétique). En situation d'environnement variable à la fois dans l'espace et le temps, les flux de gènes peuvent faciliter la diffusion d'allèles bénéfiques entre populations. L'objectif de cette thèse est d'étudier expérimentalement l'interaction entre adaptation et dispersion pollinique à longue distance sur un gradient altitudinal de hêtre commun (Fagus sylvatica). Cette étude a été conduite à partir de trois populations de hêtre sur le versant Nord du Mont-Ventoux (de 900 m à 1400 m d'altitude). Douze traits fonctionnels (phénologiques, physiologiques et morphologiques) potentiellement adaptatifs ont été mesurés sur 60 descendances maternelles issues de ces populations (20 mères/population, 100 individus/mère) et placées en pépinière. Les résultats de cette thèse montrent que (i) les forts taux de pollen immigrant reçus par les populations (m = 56 %) n'empêchent pas l'émergence de patrons de différenciation adaptative, (ii) la sélection érode la variance génétique des traits, (iii) malgré l'existence de variance génétique pour tous les traits, les covariances génétiques entre traits peuvent affecter les taux et directions d'évolution future, et (iv) les flux de pollen contribuent à augmenter la variance génétique totale au sein des populations. Finalement, les populations à moyenne et hautes altitudes pourraient avoir les capacités de s'adapter au climat futur
The rapidity of the climate change observed and predicted raises the issue of how fast species can adapt to future. In face of environmental change, populations can adapt without migrating thanks to their plastic response in a first time, and to their response to selection in the long term (genetic adaptation). In conditions of environment variable both in space and time, gene flow can enhance the spread of beneficial alleles between populations. The objective of this thesis is to experimentally measure the adaptive differentiation and the long-distance pollen dispersal along an elevational gradient of beech populations (Fagus sylvatica). In this study we investigated three beech populations located on the northern side of the Mont-Ventoux (from 900m to 1400m of elevation). Twelve potential adaptive functional traits (phenological, physiological and morphological) have been measured on 60 maternal families collected from these populations (20 mothers/population, 100 offspring/mother) and planted in nursery. The results of this thesis show that that (i) the strong pollen immigrant rate received by the populations (m = 56 %) did not their prevent adaptive differentiation, (ii) the action of natural selection erodes the genetic variance of the traits, (iii) despite significant genetic variance for all the traits, the genetic covariance between traits should affect the rate and direction of evolution in the future, and (iv) gene flow contribute to increase the total genetic variance within the populations. Finally, populations at medium and high elevations may have the potential to adapt to future climate

Ce travail se place dans le cadre des réacteurs nucléaires de 4ème génération tels que les réacteurs à neutrons rapides et caloporteur gaz (RNR-G), pour lesquels des matériaux réfractaires comme le nitrure de titane (TiN) enroberont le combustible afin de permettre la rétention des produits de fission. Cette étude a porté sur le comportement thermique intragranulaire du xénon dans des échantillons de TiN obtenus par frittage à chaud sous charge. Le rôle de la microstructure sur le comportement thermique du xénon a été étudié. Plusieurs lots ont ainsi été synthétisés sous différentes conditions de température et de composition de la poudre initiale. Le xénon a été introduit par implantation ionique. Les échantillons ont ensuite subi des traitements thermiques entre 1300°C et 1600°C, soient les températures accidentelles envisagées. Un transport majoritaire du xénon vers la surface a été mis en évidence. Ce dernier est ralenti lorsque la température de frittage augmente. Des différences de comportement ont été observées selon les poudres mises en oeuvre dans la synthèse et selon l'orientation cristalline du grain considéré. Le relâchement du xénon a également été corrélé à l'oxydation de TiN. Des bulles de Xe dès 0,38 % atomique ont été observées. Leur taille est proportionnelle à la concentration en Xe et augmente avec la température de recuit, d'où une certaine mobilité du Xe au sein de TiN. Plusieurs mécanismes pouvant expliquer cette mobilité sont proposés. En complément, des calculs ab initio ont confirmé le caractère fortement insoluble du Xe dans TiN et révélé que les bilacunes sont les plus favorables à l'incorporation du xénon au sein de ce matériau.

Ce travail se place dans le cadre des réacteurs nucléaires de 4ème génération tels que les réacteurs à neutrons rapides et caloporteur gaz (RNR-G), pour lesquels des matériaux réfractaires comme le nitrure de titane (TiN) enroberont le combustible afin de permettre la rétention des produits de fission. Cette étude a porté sur le comportement thermique intragranulaire du xénon dans des échantillons de TiN obtenus par frittage à chaud sous charge. Le rôle de la microstructure sur le comportement thermique du xénon a été étudié. Plusieurs lots ont ainsi été synthétisés sous différentes conditions de température et de composition de la poudre initiale. Le xénon a été introduit par implantation ionique. Les échantillons ont ensuite subi des traitements thermiques entre 1300°C et 1600°C, soient les températures accidentelles envisagées. Un transport majoritaire du xénon vers la surface a été mis en évidence. Ce dernier est ralenti lorsque la température de frittage augmente. Des différences de comportement ont été observées selon les poudres mises en oeuvre dans la synthèse et selon l'orientation cristalline du grain considéré. Le relâchement du xénon a également été corrélé à l’oxydation de TiN. Des bulles de Xe dès 0,38 % atomique ont été observées. Leur taille est proportionnelle à la concentration en Xe et augmente avec la température de recuit, d’où une certaine mobilité du Xe au sein de TiN. Plusieurs mécanismes pouvant expliquer cette mobilité sont proposés. En complément, des calculs ab initio ont confirmé le caractère fortement insoluble du Xe dans TiN et révélé que les bilacunes sont les plus favorables à l'incorporation du xénon au sein de ce matériau
This work concerns the generation IV future nuclear reactors such as gas-cooled fast reactor (GFR) for which refractory materials as titanium nitride (TiN) are needed to surround fuel and act as a fission product diffusion barrier. This study is about Xe thermal behavior in sintered titanium nitride. Microstructure effects on Xe behavior have been studied. In this purpose, several syntheses have been performed using differents sintering temperatures and initial powder compositions. Xenon species have been introduced into samples by ionic implantation. Then, samples were annealed in temperature range from 1300°C to 1600°C, these temperatures being the accidental awaited temperature. A transport of xenon towards sample surface has been observed. Transport rate seems to be slow down when increasing sintering temperature. The composition of initial powder and the crystallographic orientation of each considered grain also influence xenon thermal behavior. Xenon release has been correlated with material oxidation during annealing. Xenon bubbles were observed. Their size is proportional with xenon concentration and increases with annealing temperature. Several mechanisms which could explain Xe intragranular mobility in TiN are proposed. In addition with experiments, very low Xe solubility in TiN has been confirmed by ab initio calculations. So, bivacancies were found to be the most favoured Xe incorporation sites in this material

Les valvulopathies touchent 2% de la population et le premier gène identifié est le gène FLNA chez des patients présentant un prolapse mitral (PVM). Ce gène code pour la Filamine A (FLNa) qui organise le réseau cytosquelette d'actine et participe à la régulation de voies de signalisation notamment de réponse cellulaire au stress mécanique. Le but de mon travail a été de comprendre le rôle des mutations de la FLNa (G288R et P637Q) identifiées chez des patients dans le processus pathologique du PVM. Dans un modèle de ré-expression de mélanome humain, j'ai montré que les mutations de la FLNa induisent des défauts d'adhésion, d'étalement et de migration cellulaire. Ces défauts sont dus à une dérégulation de la balance des GTPases RhoA et Rac1. J'ai montré que la protéine FilGAP décrite pour interagir avec la FLNa intervient dans cette dérégulation. Les mutations de la FlnA déstabilisent aussi son interaction avec la tyrosine phosphatase PTPN12. PTPN12 étant connue pour réguler l'activité de RhoA, il est possible que la perte d'interaction FlnA/PTPN12 participe aussi à la pathologie. De plus, trois mutations sur le gène codant pour FilGAP (ARHGAP24) ont été identifiées dans 3 formes familiales de PVM. Ces mutations sont des « pertes de fonctions » car elles ne régulent plus l'activité de Rac via 2 mécanismes : 1) l'une n'est plus adressée correctement à la membrane, 2) les 2 autres n'interagissent plus avec la FLNa. Mes travaux ont mis en évidence les mécanismes moléculaires des mutations touchant des protéines (FlnA et FilGAP) impliquées dans les voies de signalisation de réponse cellulaire au stress mécanique qui sont très sollicitées dans les valves cardiaques
The prevalence of heart valve disease is 2% of population et the first gene identified is the FLNA gene on patients with Mitral Valve Prolapse (MVP). This gene encodes for Filamin A which organizes the actin cytoskeleton network et participates in many signaling pathways particularly in mechanical stress response. The aim of my work is to identify the role of FLNa mutations identified in patient with pathological MVP. In the re-expression of a human melanoma cell model, I showed that FLNa mutations lead to an adhesion, spreading et migration impairment. These impairments are due to a deregulation of the small GTPases activities – Rho et Rac. I have shown that FilGAP, known to interact with FLNa, participates to this deregulation. FlnA mutations destabilize its interaction with PTP-PEST. Higher RhoA activity is due to the loss of FLNa-PTP-PEST interaction. PTP-PEST is known to regulate RhoA activity et there is a possibility that the loss of interaction participates to the pathological processes. Moreover, 3 mutations on the ARHGAP24 gene, which encodes for FilGAP, were identified on 3 familial forms. These mutations are “loss of function” because they can regulate Rac activity through 2 mechanisms: 1) One of them is not correctly addressed in the membrane et 2) The two others are not able to interact with FLNa. My work showed 2 molecular mechanisms of mutation that affected 2 proteins (FLNa-FilGAP) involved in mechanical stress signaling pathways which are very important in heart valves

Nous presentons l'etude de nouvelles donnees experimentales au + au a 150 et 400 a. Mev obtenues avec le detecteur fopi. Nous etudions principalement le flot, determine a partir de la methode de danielewicz sans reconstruction du plan de reaction et le pouvoir d'arret de la matiere en fonction de la charge des fragments et en fonction de la centralite des collisions. Nous comparons ensuite les donnees experimentales avec differentes versions du modele qmd afin d'etudier les effets de milieu nucleaire sur les sections efficaces et sur le potentiel n-n. La premiere version (gqmd) utilise le formalisme de matrice g pour calculer de maniere microscopique les sections efficaces et les potentiels. Cette version inclue donc naturellement les effets de milieu nucleaire. La seconde version (iqmd) utilise un potentiel de skyrme et un terme dependant de l'impulsion pour reproduire les effets de milieu. Le pouvoir d'arret est surrestime par les deux versions du modele. En ce qui concerne le flot, la dependance en impulsion est plus grande dans gqmd et permet de reproduire les evenements plus peripheriques. Par contre, le modele gqmd qui possede une equation d'etat soft manque de dependance en densite pour reproduire les evenements centraux. Cette comparaison montre donc qu'une equation d'etat hard est necessaire pour reproduire le flot dans les collisions centrales et qu'une grande dependance en impulsion permet de reproduire les collisions semi-centrales et peripheriques

L'etude morphologique des capillaires de la moelle epiniere montre que la substance grise est plus vascularisee que la substance blanche, et qu'il n'y a pas de difference statistiquement significative quant au diametre interne des capillaires et a l'epaisseur de la lame basale capillaire de ces deux regions. Les pericytes sont presents dans le dedoublement de la lame basale de la quasi-totalite de ces capillaires. Une partie de ces derniers sont entoures d'un espace clair, non opaque aux electrons, separant la lame basale capillaire de la lame basale astrocytaire. Cet espace contient des cellules dont l'aspect morphologique n'est ni celui d'un peeicyte, ni celui d'une cellule nerveuse ou gliale. Au niveau de l'endothelium de ces capillaires, il existe une barriere hemato-medullaire qui empeche la diffusion des immunoglobulines g dans le compartiment extravasculaire. En revanche une barriere impermeable n'existe pas au niveau du ganglion spinal et les immunoglobulines g diffusent dans l'espace perivasculaire. Les collagenes de type un, trois, quatre, la laminine et la fibronectine sont presents dans la moelle epiniere. Ils sont localises dans les tissus de nature conjonctive, notamment les lames basales, le sillon median et les enveloppes meningees. Les collagenes de type un, trois et la fibronectine sont en plus retrouves au niveau de l'ependyme

La nature extraordinaire du r??gime national-socialiste a longtemps paralys?? les tentatives d???en expliquer les causes, les m??canismes et les assises id??ologiques. Pourtant, depuis les ann??es 1960 et de mani??re toujours croissante par la suite, il s???av??re que ce qu???il y a de plus significatif sur le Troisi??me Reich semble ??tre r??v??l?? gr??ce ?? son inscription dans une trame sociohistorique qui le d??passe. En ce sens, la tendance misogyne du r??gime nazi ne peut ??tre comprise que par un exercice g??n??alogique. Caract??ristique fondamentale souvent n??glig??e, l???antif??minisme nazi s???inscrit dans une tendance paternaliste occidentale qui, bien qu???elle n???explique pas ?? elle seule les politiques et mesures nazies concernant les femmes, permet de saisir la nature id??ologique de leurs motivations. Plongeant au c??ur d???un XIXe si??cle post-Lumi??res aux contradictions nombreuses, aux revendications sociales certaines et aux maintes red??finitions ??pist??mologiques provoqu??es, entre autres, par le mouvement ?? anti-Lumi??res ??, notre m??moire propose d???observer les ??chos du discours allemand sur la diff??renciation des sexes et les femmes sous le Troisi??me Reich. Les id??es nazies sur les femmes ne naissent ainsi pas ex nihilo ; elles s???inscrivent dans une r??cup??ration id??ologique et une continuit?? philosophique. Tant les philosophes Arthur Schopenhauer, Friedrich Nietzsche et Otto Weininger que le m??decin Paul M??bius et le sociologue Georg Simmel s???expriment abondamment sur la ?? question f??minine ??. Repr??sentants du discours allemand de la seconde moiti?? du XIXe si??cle et du premier tiers du XXe si??cle, ils s???inscrivent ??videmment dans la tendance europ??enne, voire occidentale, d???une remise en question des acquis des Lumi??res et des revendications f??ministes. Se pronon??ant tant sur le corps f??minin que sur les capacit??s intellectuelles et morales des femmes, ces penseurs discr??ditent le mouvement d?????mancipation f??minine et mettent de l???avant des valeurs in??galitaires et d??terministes qui caract??riseront ??galement l???Allemagne d???Hitler.

La tesi si propone come uno studio sulla risoluzione angolare per il tracciamento di particelle nell’esperimento MUonE. La proposta di questo è quella di misurare, con un’elevata precisione, il contributo adronico al running della costante di accoppiamento aEM nella regione space-like, attraverso lo scattering ad alta energia di muoni su elettroni atomici di un bersaglio di grafite. Per mezzo della misura della sezione d’urto differenziale elastica del processo, si potrà misurare il contributo adronico dominante aHLO all’anomalia μ del momento magnetico g − 2 del muone. Questa misura richiede un’analisi precisa delle incertezze date da effetti fisici come Multiplo Scattering Columbiano (MSC) e bremsstrahlung. La mia analisi sarà concentrata sull’effetto legato al MSC e, in virtù di questo, sulla valutazione della configurazione ottimale dell’apparato di tracciamento. Si è simulato il sistema di rilevamento e N eventi di hit sui pannelli di questo. In seguito si è usato un metodo di adattamento ai minimi quadrati, attraverso la matrice di covarianza degli errori sulle coordinate, per stimare la direzione della particella nella simulazione. Si sono raccolti gli angoli risultanti in un istogramma, la cui sigma rappresenta l’incertezza del sistema. Si sono valutate la dipendenza dell’incertezza dall’energia della particella e dai parametri geometrici del fascio per poi valutare la configurazione ideale che rende minima la risoluzione angolare.

O principal objetivo deste estudo foi investigar os processos responsáveis pela evolução morfológica craniana de primatas da subordem Strepsirrhini, com maior ênfase ao clado endêmico à ilha de Madagascar. Sistemas multidimensionais morfológicos como o crânio descrevem a quantidade de variação disponível para atuação de processos evolutivos. A partir de 27 marcos anatômicos cranianos e 39 distâncias euclidianas estimei matrizes de variância e covariância fenotípicas (Matrizes P) para 40 espécies das sete famílias viventes de Strepsirrhini e duas espécies do gênero Tarsius. Utilizei a abordagem da genética quantitativa para investigar o padrão de variação nas matrizes P dessa linhagem de primatas, conjuntamente com um par de matrizes fenotípica e genética de Saguinus fuscicolis. Para investigar a estabilidade e conservção do padrão da estrutura de variação ao longo da diversidade deste clado de primatas compararei estas matrizes através de dois métodos complementares que me permitiram avaliar a distribuição da variação no morfoespaço (Random Skewers) e o compartilhamento de direções de variação (Krzanowski) das matrizes. Os resultados obtidos sugerem uma estabilidade das matrizes, possivelmente mantida por seleção estabilizadora interna comum ao clado, aos demais primatas e mamíferos em geral. Esses resultados de comparação de matrizes são apresentados no Capítulo 1 e corroboram a conjectura de Cheverud, indicando que as matrizes cumprem o pressuposto de similaridade estrutural entre as matrizes P e a matriz G. Além disso o padrão de variação apresentou um sinal filogenético e algumas das diferenças observadas nas matrizes parecem estar relacionadas com fatores de dieta. No Capítulo 2 investiguei a evolução da divergência morfológica craniana em um conjunto de 70 espécies, onde testei a hipótese nula de deriva genética como explicação suficiente para a divergencia entre as médias das espécies. Esta hipótese foi avaliada dentro das expectativas de modelos da genética quantitativa através de duas metodologias. Tais testes avaliam a proporcionalidade de variação dentro (W) e entre grupos (B) sob perspectivas complementares. Com o teste de regressão investiguei a manutenção da quantidade de variação associada a cada eixo de variação, e com o teste de correlação avaliei o alinhamento entre estes eixos. Rejeitamos a H_0 em diversos pontos da árvore que representam eventos de cladogenese a nível de família e gênero. Nestes casos aceitamos a H_1 de seleção natural e vemos que a maior parte da diversificação da linhagem de primatas de Madagascar foi influenciada por seleção direcional envolvendo tamanho e alterações anatômicas relacionadas a dieta
The main goal of this study was to investigate the evolutionary processes responsible for Strepsirrhini cranial morphological evolution. Multidimensional morphological structures like the cranium can describe the amount of variance available to evolution. We used 27 landmarks and 39 euclidean distances between them to describe the variation in the cranium. We used a broad phylogenetic scaled comparison of cranial P matrices representing 40 species of Strepsirrhini primates combined to a pair of Saguinus fuscicolis G and P to investigate the stability of variance structure along this lineage. Our results show a relative stability in the patterns of variance and covariance of the clade and that P matrices can be considered as surrogates to its underling G. We also report a high association between matrix similarity and phylogenetic distance. We investigated particular contributions of each trait to matrix dissimilarity through a evolutionary perspective considering the main dietary shifts observed in the clade. Our results suggest that differences in observed patterns of variation can be attributed to characters with heterogeneity in the degree of stabilizing selection in the adult cranium and to differences in directional selection involved in chewing of specialized feeding behavior. Under the quantitative genetics theory lies an expectation for the evolution of average phenotypes that if populations have diverged by random processes, patterns of within and between-taxon morphological variation should be proportional. In chapter 2 we tested the null hypothesis that genetic drift is a sufficient explanation to observed divergence in cranial multivariate means of 70 Strepsirrhini primates. We detected deviations from neutrality along the whole clade of Strepsirrhini and specially in more inclusive nodes. We argue that this deviations reflect important historical shifts in the evolution of the clade associated with directional selection for size and in anatomical features related with diet

[EN] Several authors have studied the Hadamard product or entry wise product of two matrices with di erent objectives. In particular, the product of a Hadamard matrix and the transpose of its inverse has proved useful in many areas such as in the study of chemical processes. This product is called combined matrix and is denoted by C(A). The combined matrix also has various applications in the eld of linear algebra. For example, from the combined matrix an interesting relationship between the eigenvalues and the diagonal elements of a diagonal- izable matrix is obtained. Furthermore, since the sum of each row and each column of a combined matrix is exactly equal to 1, in cases where the combined matrix is nonnegative, C(A) will be a doubly stochastic matrix. The study of properties of C(A) is still under research and many results have recently been published. Herein are collected and extended results concerning the combined matrix of some classes of matrices related to positivity? For this, a long list of related works has been consulted and a summary of the most relevant results has been made before showing the new results. The interest of some open issues was also raised. The memory is structured as follows. In the rst chapter the concepts are de ned and listed. General results are proven that will be used in the rest of the memory. In the three remaining chapters, we present the problems to solve, the results we have obtained and summarize their interest as conclusions. In Chapter 2 it is determined whether the combined matrix of some clas- sic classes of matrices may or may not be doubly stochastic. The combined matrix of these classes is studied and we concluded that the positivity of the combined matrix is obtained for some G-matrices, some H-matrices and some 2x 2 matrices. It never occurs to completely positive or completely negative ma- trices; and only it is obtained that C(A) 0 when C(A) = I in the case where A is not completely negative or M-matrix. Finally, only totally non positive anti-triangular matrices of size 2x2 have its combined matrix nonnegative. In Chapter 3 the previous study is extended to sign-regular matrices. The sign of the entries of the combined matrix from the signature of the matrix and of its inverse matrix transpose is analyzed and a list with all possible cases is obtained. This list shows cases where C(A) is never negative and others where C(A) is nonnegative when it is a diagonal or anti-diagonal matrix, that is, only when C(A) coincides with the identity matrix I or the anti-identity J. Likewise, it follows that the sign of the elements in C(A) is determined solely by the rst two and the last two elements of the symbol of A. In Chapter 4, we determine relations between the diagonal elements of the combined matrix of a totally negative matrix and thereby we characterize when a given vector can be the diagonal entries of C(A). Thus, relations between the rst two and last two diagonal elements of C(A), both for symmetric and non- symmetric cases are obtained. The diagonal of a combined matrix of a totally negative matrix of dimension 3x3 is also characterized. Finally, a chapter is written with all our achievements and a short list of possible future lines of work upon aspects that the author of this report would like to continue studying in order to reach new related goals.
[ES] El producto de Hadamard o producto elemento a elemento de dos matrices ha sido estudiado por diversos autores con diferentes objetivos. En particular, el producto de Hadamard de una matriz y la traspuesta de su inversa ha de- mostrado su utilidad en múltiples áreas como por ejemplo en el estudio de procesos químicos. Este producto se denomina matriz combinada y se denota por C(A). La matriz combinada tiene además diversas aplicaciones en el ámbito del álgebra lineal. A partir de la matriz combinada se obtiene, por ejemplo, una interesante relación entre los valores propios y los elementos diagonales de una matriz diago- nalizable. Además, dado que la suma de cada fi la y de cada columna de una matriz combinada es exactamente igual a 1, en aquellos casos en que la matriz combinada sea no negativa, C(A) será una matriz doblemente estocástica. El es- tudio de propiedades de C(A) sigue siendo de actualidad y muchos resultados han sido publicados recientemente. En esta memoria se recogen y amplían los resultados referentes a la matriz combinada de algunas clases de matrices relacionadas con la positividad. Para ello se ha consultado una larga relación de trabajos relacionados y se ha realizado un resumen de los resultados más relevantes antes de incluir los nuevos resultados. Se plantea también el interés de algunas cuestiones abiertas. La memoria se estructura de la siguiente manera. En el primer capítulo se de nen los conceptos y se enuncian y/o demuestran los resultados de ámbito general que van a ser utilizados en el resto de la memoria. En los tres restantes capítulos se plantea el tipo de problema a resolver, se enuncian y demuestran los resultados obtenidos y se resume su interés a modo de conclusiones. En el Capítulo 2 se determina si la matriz combinada de clásicas clases de matrices puede ser o no doblemente estocástica. Se estudia la matriz combinada de estas clases y se concluye que se obtiene la positividad de la matriz combinada para algunas G-matrices, algunas H-matrices y algunas matrices 2x2; nunca se da para matrices totalmente positivas o totalmente negativas; y s'olo se obtiene C(A) mayor o igual que 0 cuando C(A) = I en el caso de que A sea totalmente no negativa o M-matriz. Por último, sólo las matrices anti-triangulares totalmente no positivas de tamaño 2x2 tienen matriz combinada no negativa. En el Capítulo 3 se extiende el estudio anterior a matrices signo-regulares. Se analiza el signo de las entradas de la matriz combinada a partir de la signatura de la matriz y de la signatura de su matriz inversa traspuesta y se obtiene una lista con todos los casos posibles. Esta lista muestra casos en los que C(A) nunca es no negativa y otros en los que C(A) es no negativa cuando es una matriz diagonal o anti-diagonal, esto es, sólo cuando C(A) coincide con la matriz identidad, I, o con la anti-identidad, J. Así mismo, se deduce que el signo de los elementos de C(A) viene determinado únicamente por los dos primeros y los dos últimos elementos de la signatura de A. En el Capítulo 4 se busca determinar relaciones entre los elementos diagonales de la matriz combinada de una matriz totalmente negativa y con ello caracterizar cuándo cierto vector puede coincidir con la diagonal de C(A). Así, se obtienen relaciones entre los dos primeros y dos últimos elementos de la diagonal de C(A), tanto para el caso simétrico como no simétrico. También se caracteriza la diagonal de la matriz combinada de una matriz totalmente negativa de dimensión 3x3. Finalmente, se incluye un capítulo donde se resume los logros alcanzados y un pequeño listado de las posibles líneas futuras de trabajo sobre aspectos que el autor de esta memoria querría continuar estudiando en vista a unos nuevos objetivos.
[CAT] El producte de Hadamard o producte element a element de dues matrius ha sigut estudiat per diversos autors amb diferents objectius. En particular, el pro- ducte de Hadamard d'una matriu i la trasposta de la seua inversa ha demostrat la seua utilitat en mltiples rees com per exemple en l'estudi de processos qumics. Aquest producte es denomina matriu combinada i es denota per C(A). La ma- triu combinada t a ms diverses aplicacions en l'mbit de l'lgebra lineal. A partir de la matriu combinada s'obt, per exemple, una interessant relaci entre els val- ors propis i els elements diagonals d'una matriu diagonalizable. A ms, ats que la suma de cada la i de cada columna d'una matriu combinada s exactament igual a 1, en aquells casos en qu la matriu combinada siga no negativa, C(A) ser una matriu doblement estocstica. L'estudi de propietats de C(A) segueix sent d'actualitat i molts resultats han sigut publicats recentment. En aquesta memria s'arrepleguen i amplien els resultats referents a la matriu combinada d'algunes classes de matrius relacionades amb la positividad. Per a a s'ha consultat una llarga relaci de treballs relacionats i s'ha realitzat un resum dels resultats ms rellevants abans d'incloure els nous resultats. Es planteja tamb l'inters d'algunes qestions obertes. La memria s'estructura de la segent manera. En el primer captol es de- neixen els conceptes i s'enuncien i/o demostren els resultats d'mbit general que van a ser utilitzats en la resta de la memria. En els tres restants captols es planteja el tipus de problema a resoldre, s'enuncien i demostren els resultats obtinguts i es resumeix el seu inters a manera de conclusions. En el Captol 2 es determina si la matriu combinada de clssiques classes de matrius pot ser o no doblement estocstica. S'estudia la matriu combinada d'aquestes classes i es conclou que s'obt la positividad de la matriu combinada per a algunes G-matrius, algunes H-matrius i algunes matrius 2 x2; mai es dna per a matrius totalment positives o totalment negatives; i noms s'obt C(A) 0 quan C(A) = I en el cas que A siga totalment no negativa o M-matriu. Finalment, noms les matrius anti-triangulars totalment no positives de grandria 2x2 tenen matriu combinada no negativa. En el Captol 3 s'estn l'estudi anterior a matrius signe-regulars. S'analitza el signe de les entrades de la matriu combinada a partir de la signatura de la matriu i de la signatura de la seua matriu inversa trasposta i s'obt una llista amb tots els casos possibles. Aquesta llista mostra casos en els quals C(A) mai s no negativa i uns altres en els quals C(A) s no negativa quan s una matriu diagonal o anti-diagonal, a s, noms quan C(A) coincideix amb la matriu identitat I o amb la anti-identitat J. Aix mateix, es dedueix que el signe dels elements de C(A) ve determinat nicament pels dos primers i els dos ltims elements de la signatura de A. En el Captol 4 se cerca determinar relacions entre els elements diagonals de la matriu combinada d'una matriu totalment negativa i amb a caracteritzar quan cert vector pot coincidir amb la diagonal de C(A). Aix, s'obtenen relacions entre els dos primers i dos ltims elements de la diagonal de C(A), tant per al cas simtric com no simtric. Tamb es caracteritza la diagonal de la matriu combinada d'una matriu totalment negativa de dimensi 3x3. Finalment, s'inclou un captol on es resumeix els assoliments aconseguits i un petit llistat de les possibles lnies futures de treball sobre aspectes que l'autor d'aquesta memria voldria continuar estudiant en vista a uns nous objectius.
Santana De Asís, MDJ. (2015). MATRICES COMBINADAS DE ALGUNOS TIPOS DE MATRICES [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/48806
TESIS

Let F be a field and G a group. In this dissertation, we deal with the G-gradings of the algebra of upper triangular matrices over F, based on Valenti and Zaicev's articles on the subject. We start by the 2x2 matrices case, which shows in a simpler manner the techniques used on the more general cases. We then deal with the case where n is arbitrary, but first will restrict ourselves to the case F is an algebraically closed field of characteristc zero and G an finite abelian group. Lastly, we will do the general case: If F is any field and G any group, then every G-grading of the algebra of upper triangular matrices over F is isomorphic to a kind we call elementary.
Sejam F um corpo e G um grupo. Nesta dissertação, trataremos das G-graduações da álgebra de matrizes triangulares superiores sobre F, a partir dos artigos de Valenti e Zaicev sobre o assunto. Começaremos pelo caso das matrizes 2 x 2, que ilustra de forma mais simples as técnicas usadas nos casos mais gerais. Passaremos então ao caso em que n é arbitrário, mas nos restringiremos primeiramente ao caso em que F é um corpo algebricamente fechado de característica zero e G um grupo abeliano finito. Por fim, faremos o caso geral: Para F um corpo qualquer e G um grupo qualquer temos que toda G-graduação da álgebra de matrizes triangulares superiores sobre F é, a menos de isomorfismo, de um tipo que chamamos elementar.

Sistemas morfológicos quantitativos são descritos por medidas contínuas. A relação genética entre essas características dos indivíduos é representada pela matriz de covariância genética aditiva, a matriz G. Entender a evolução da matriz G, portanto, é de suma importância para compreender os padrões de diversificação encontrados na natureza. Neste trabalho estudamos modelos computacionais para a evolução de traços contínuos em populações naturais, sujeitas a variados tipos de seleção e condições internas, focando no problema da evolução dos padrões de integração e modularidade nessas populações. Testamos dois modelos com diferentes combinações de parâmetros em sua capacidade de reproduzir e elucidar padrões naturais. Seleção direcional correlacionada se mostrou uma força importante na criação desses padrões de covariação e a seleção estabilizadora correlacionada se mostrou fundamental para a manutenção desses padrões
Quantitative morphological systems are described by continuous measurements. The genetic relation between these characteristics of the individuals is represented by the genetic additive co-variance matrix, the G matrix. Understanding the evolution of the G matrix is, therefore, of paramount importance for proper interpretation of the patterns of diversification we observe in nature. In this work we study computational models for the evolution of quantitative traits in natural populations, subject to different natural selection and internal conditions, focusing on the problem of the evolution of the pattern of morphological integration and modularity. We test two models with different sets of parameters in their ability to reproduce and elucidate natural patterns. Directional correlated selection was necessary for the shaping of the patterns of morphological integration, and correlated stabilizing selection was fundamental to the maintenance of these patterns

La progression métastatique des cancers est responsable de 90% des décès liés à la maladie. Cette cascade est initiée par l’invasion des cellules cancéreuses du stroma péritumoral, et conduit à leur dissémination dans l’organisme.Mon travail de thèse a eu pour but d’identifier les mécanismes moléculaires et cellulaires régulant l’invasion des cancers colorectaux (CRC), qui est le 2ème cancer le plus répandu dans le monde. Grâce à une analyse réalisée sur des échantillons humains de tumeurs primaires, nous avons révélés que les cellules de CRC utilisent un mode d’invasion collective dans lequel elles gardent une architecture glandulaire spécifique des épithelia. Afin d’étudier les voies de signalisation régulant cette invasion, nous avons utilisé des modèles organotypiques récapitulant l’architecture des glandes de CRC (cystes de Caco-2 et tumoroïdes de xénogreffes derivés de patients) dans des tests d’invasion utilisant du collagen-I. Du fait de son rôle central dans la régulation de la motilité cellulaire, la voie des RhoGTPases était un bon candidat à la régulation de l’invasion collective des CRC. Dans un screen utilisant des siRNA ciblant tous les effecteurs connus des RhoGTPases, seule la déplétion des protéines kinases ROCK a déclenché l’invasion collective dans notre système expérimental. Nous avons démontré que l’inhibition de ROCK2 et non de ROCK1 était suffisante pour induire la formation de cellules leader, permettant la polarisation leader/follower requise pour l’invasion collective. Nos résultats montrent que l’inhibition de ROCK2 déclenche l’invasion collective par l’inhibition de MyosinII combinée à l’activation du facteur d’échange nucléotide guanine (GEF), FARP2, et de RAC1. Notre étude permet donc d’identifier FARP2 comme un nouvel effecteur de ROCK2 et le positionne comme un nouveau médiateur du crosstalk entre RhoA et RAC1 dans la régulation de l’invasion collective des CRC. En conclusion, nous avons décrit une nouvelle voie de signalisation dépendante de ROCK2 contrôlant l’invasion collective de glandes de CRC. De façon intéressante, notre étude révèle un rôle anti-invasive de ROCK2 contredisant son rôle pro-invasive décrit dans l’invasion de cellules individuelles. Cela suggère que ROCK2 assure des rôles distincts en fonction du mode d’invasion adopté par les cellules cancéreuses et remet en question le bénéfice thérapeutique de l’inhibition de ROCK proposé pour bloquer l’invasion des cellules cancéreuses
Metastatic progression of cancer is responsible for 90% of the disease related death. It is a multi-step process which is initiated by invasion of the peritumoral stroma by cancer cells and which leads to the dissemination of cancer cells in the organism.My PhD work aimed at identifying the molecular and cellular process driving colorectal carcinoma (CRC) invasion, which is the 2nd most frequent cancer worldwide. Our analysis of live and human primary cancer specimen revealed that CRC cells used a collective mode of invasion to disseminate, in which cells retain an epithelium specific -glandular architecture. To investigate the signaling pathways regulating this mode of invasion, we used 3D organotypic models recapitulating the features of CRC glands (Caco-2 cysts and Patient derived Xenografts (PDX) tumoroids) in collagen-I based organotypic invasion assays and in microscopy-based analyses. Because of its central role in the regulation of cell motility, we postulated that RhoGTPases signaling pathways could control the collective of CRC. In a siRNA based- screen targeting all the known effectors of RhoGTPases we found that only ROCK kinases downregulation induced collective invasion in our experimental settings. We demonstrated that ROCK2 but not ROCK1 inhibition was sufficient to promote Leader cell formation, which induced the leader/follower polarization necessary for collective invasion. Our results revealed that ROCK2 inhibition triggered collective invasion through the concomitant inhibition of MyosinII and activation of the guanine nucleotide exchange factor (GEF) FARP2 and the RhoGTPase RAC1. We therefore identify FARP2 as a new effector of ROCK2 and a mediator of the RhoA-RAC1 crosstalk in the regulation of collective invasion. In conclusion our study proposes a new ROCK dependent-signaling pathway in the regulation of collective invasion of highly polarized CRC glands models. Importantly, we found ROCK2 to be an anti-invasive protein which is in contradiction with its described pro-invasive role in single cell invasion. This suggests distinct roles of ROCK which may depend on the mode of invasion adopted by the cells and questions the benefice of proposed ROCK inhibition strategies to block cancer cell invasion

Orientadores: Sonia Maria Alves Bueno, Paulo de Tarso Vieira e Rosa
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica
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Resumo: A técnica de adsorção por afinidade, que utiliza adsorventes com alta seletividade para adsorver compostos, principalmente proteínas, tem sido empregada para remover autoanticorpos do plasma de pacientes com doenças auto-imunes e também na produção em larga escala de drogas terapêuticas através do ftacionamento do plasma humano ou animal. Na circulação extracorpórea o plasma do paciente é alimentado em uma coluna contendo um ligante imobilizado em uma matriz insolúvel que remove os auto-anticorpos, e as proteínas não adsorvidas retomam para o paciente sem nenhuma alteração. Na busca de sistemas adequados para a aplicação no tratamento de doenças auto-imunes, esta pesquisa investiga a adsorção de IgG em dois suportes de afinidade empregando a histidina como ligante, imobilizado em membranas de fibras ocas de álcool poli etileno vinílico (pEV A) e gel de copolímero de metacrilato (Toyopearl), denominados His-PEV A e His- Toyopearl, respectivamente. Sendo verificada a possibilidade de adsorção de IgG em ambos suportes, experimentos de seletividade e de capacidade de adsorção em modo dinâmico e estático demonstraram uma maior eficiência para o sistema His-PEV A do que para o HisToyopearl, tanto na presença do tampão Hepes a pH 7,0 como do Tris-HCI pH a 7,4. Através da obtenção de isotermas de adsorção, para os suportes com e sem ligante, à temperatura ambiente e à 37 °C, foi constatada a existência de interações não-específicas entre a proteína e a matriz, sendo necessário efetuar as etapas de lavagem, eluição e regeneração, após ser atingido o equilíbrio de adsorção, para obter a quantidade de proteína adsorvida especificamente nos suportes. A determinação de parâmetros como a capacidade máxima de adsorção, a constante de dissociação do complexo IgG-histidina (KJ) e as constantes cinéticas de adsorção (Iça) de dessorção (kd) de proteína, indicaram que apesar de ambos sistemas apresentarem uma afinidade pela proteína da mesma ordem de grandeza (lO-sM), o suporte His-PEV A apresenta uma maior capacidade para a adsorção específica de proteína, nas temperaturas analisadas
Abstract: Affinity adsorption explores the characteristics that certain compounds have to selectively interact with substances or classes of substances. This technique has been used to purify proteins in small and large scale and also to remove autoantibodies from plasma of autoimmune patients. In an extracorporeal treatment, the autoantibodies are retained in a column that contains an affinity ligand immobilized in an insoluble matrix. The unretained fraction containing the plasma proteins different from the autoantibodies can be returned to the patient. In this work, the behavior of IgG adsorption either onto poly ethylene vinyl alcohol (pEV A) hollow-fiber membranes or onto metacrylate gels (Toyopearl) containing histidine as affinity ligand was studied. The IgG adsorption in both supports was feasable. The selectivity studies as well as the static and dynamic adsorption experiments showed that the IgG adsorption onto PEV A hollow-fibers was more efficient than onto Toyopearl, independently ifHepes pH 7.0 or Tris-HCI 7.4 buffer were used. The adsorption isotherms of IgG in the supports with or without ligand showed that there is also non-specific adsorption of the protein onto the matrix surface. The amount of specifically adsorbed protein was determined by the elution and regeneration of the support following extensive washing of the particles with buffer. The values of the adsorption capacity constant (Qm), dissociation constant of the IgG-histidine complex (Kd), adsorption constant (ka), and desorption constant (kd) indicated that both systems have approximately the same affinity for the IgG (10.5 M) and that PEV A hollow-fibers have a large specific adsorption capacity. This behavior was observed for temperatures of25 and 37°C
Mestrado
Desenvolvimento de Processos Biotecnologicos
Mestre em Engenharia Química

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The underground natural gas found associated or not with oil is characterized by a mixture of hydrocarbons and residual components such as carbon dioxide (CO2), nitrogen gas (N2) and hydrogen sulfide (H2S), called contaminants. The H2S especially promotes itself as a contaminant of natural gas to be associated with corrosion of pipelines, to human toxicity and final applications of Natural Gas (NG). The sulfur present in the GN must be fully or partially removed in order to meet the market specifications, security, transport or further processing. There are distinct and varied methods of desulfurization of natural gas processing units used in Natural Gas (UPGN). In order to solve these problems have for example the caustic washing, absorption, the use of membranes and adsorption processes is costly and great expenditure of energy. Arises on such findings, the need for research to active processes of economic feasibility and efficiency. This work promoted the study of the adsorption of sulfide gas in polymer matrices hydrogen pure and modified. The substrates of Poly(vinyl chloride) (PVC), poly(methyl methacrylate) (PMMA) and sodium alginate (NaALG) were coated with vanadyl phosphate compounds (VOPO4.2H2O), vanadium pentoxide (V2O5), rhodamine B (C28H31N2O3Cl) and ions Co2+ and Cu2+, aiming to the adsorption of hydrogen sulfide gas (H2S). The adsorption tests were through a continuous flow of H2S in a column system (fixed bed reactor) adsorption on a laboratory scale. The techniques used to characterize the adsorbents were Infrared spectroscopy (FTIR), thermogravimetry analysis (TGA), X-ray fluorescence (XRF), the X-ray diffraction (XRD) electron microscopy (SEM). Such work indicates, the results obtained, the adsorbents modified PMMA, PVC and NaALG have a significant adsorptive capacity. The matrix that stood out and had the best adsorption capacity, was to ALG modified Co2+ with a score of 12.79 mg H2S / g matrix
O g?s natural encontrado no subsolo associado ou n?o ao petr?leo se caracteriza por uma mistura de hidrocarbonetos e componentes residuais tais como o di?xido de carbono (CO2), o g?s nitrog?nio (N2) e o sulfeto de hidrog?nio (H2S), denominados de contaminantes. O H2S em especial se promove como contaminante do g?s natural por estar associado ? corros?o de dutos (gasodutos), ? toxidade humana e a aplica??es finais do G?s Natural (GN). O teor de enxofre presente no GN deve ser totalmente ou parcialmente removido, visando atender as especifica??es de mercado, seguran?a, transporte ou processamento posterior. H? distintos e variados m?todos de dessulfuriza??o do g?s natural usados nas Unidades de Processamento do G?s Natural (UPGN). Visando solucionar tais problemas temos como exemplo a lavagem c?ustica, a absor??o, o uso de membranas e a adsor??o, sendo processos onerosos e com grande disp?ndio energ?tico. Surge, diante de tais constata??es, a necessidade de pesquisa de processos ativos de viabilidade econ?mica e efici?ncia. O presente trabalho promoveu o estudo da adsor??o do g?s sulfeto de hidrogr?nio em matrizes polim?ricas puras e modificadas. Os substratos de Poli(cloreto de vinila) (PVC), Poli(metacrilato de metila) (PMMA) e alginato de s?dio (NaALG), foram recobertos com os compostos de fosfato de vanadila (VOPO4.2H2O), pent?xido de van?dio (V2O5), rodamina B (C28H31N2O3Cl) e os ?ons Co2+ e Cu2+, objetivando-se a adsor??o do g?s sulfeto de hidrog?nio (H2S). Os ensaios de adsor??o se deram atrav?s de um fluxo cont?nuo de H2S em um sistema de coluna (reator de leito fixo) de adsor??o em escala de laborat?rio. As t?cnicas utilizadas para a caracteriza??o dos adsorventes foram ? espectroscopia de infravermelho (FTIR), a an?lise termogravimetria (TG), a fluoresc?ncia de raios X (FRX), o difra??o de raios X (DRX), a microscopia eletr?nica de varredura (MEV). Tal trabalho indica, pelos resultados obtidos, que os adsorventes modificados de PMMA, PVC e NaALG t?m uma capacidade adsortiva significativa. A matriz que se destacou e apresentou a melhor capacidade de adsor??o, foi a de ALG modificada com Co2+ tendo um resultado de 12,79 mg de H2S/g de matriz

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O tema central desta dissertação é a descrição das identidades polinomiais graduadas da álgebra Mn(K). Métodos diferentes são empregados conforme a característica do corpo: se Char K = 0, à descrição das identidades graduadas se reduz a descrição das identidades multilineares, o que foi feito no Capítulo 2, onde são descritas as identidade de Mn(K) com uma classe ampla de graduações elementares; se Char K =p>0 e K é in nito, a descrição das identidades graduadas é reduzida à descrição das identidades multi-homogêneas, que torna o problema mais difícil, e técnicas como a construção de álgebras genéricas são necessárias. No Capítulo 3 são descritas as identidades Z e Zn-graduadas de Mn(K) para um corpo in nito K.
The main theme of this dissertation is the description of the graded polynomial identities of the algebra Mn(K). Diferent methods are used depending on the characteristic of the field: if Char K = 0, the description of the graded identities is reduced to the description of the multilinear graded identities, what was done in Chapter 2, where the identities of Mn(K) are described for a wide class of elementary gradings; if Char K =p>0 and K is in nite, the description of the graded identities is reduced to the study of the multi-homogeneous identities, wich makes it harder, and techniques such as the construction of generic algebras are necessary. In Chapter 3 the Z and Zn-graded identities of Mn(K) are described for an infinite field K

L’étude des réaction (a,g) d’intérêt astrophysique est vaste. Ces réactions ont un rôle important dans la phase de fusion d’hélium des étoiles, dans la nucléosynthèse au moment du big bang ainsi que dans une grande partie des scénarios d'explosions stellaires. L’étude des réactions (a,g) impliquant des faisceaux stables peut être réalisée de diverse façon. Je me suis concentrée sur deux d'entre elles. La première est l’étude en cinématique directe en détectant les rayons gamma produits. C'est ce que j'ai fait durant ma thèse pour mesurer la section efficace de 7Li(a,g)11B. Cette réaction a été étudiée au cours des années pour différentes raisons en astrophysique nucléaire. Par exemple, il a été postule que cette réaction pourrait résoudre, au moment de la nucléosynthèse du big bang, le problème du Lithium. Il est clair, aujourd'hui, que ce n'est pas la solution, cependant, elle a un rôle dans la production de boron lors des supernovae de type Ic. Une autre façon d’étudier les réactions (a,g) est d'utiliser la cinématique inverse. L’idée est d'envoyer un faisceau d'ions lourd sur une cible d’hélium. Ce type de cinématique permet de détecter, avec une bonne efficacité, le noyau lourd de recul produit si le faisceau qui n'a pas interagit avec la cible, en est correctement séparé. Les séparateurs de masses, comme St. George, sont construit dans ce but. St. George sera impliquer dans la mesure de sections efficaces de réaction d’importance pour le processus s comme 16O(a,g)20Ne
The study of (a,g) reactions of astrophysical interest is quite vast. These reactions play an important role in the quiescent Helium burning phase of stars, in big bang nucleosynthesis and in most explosive stellar scenarios. The studies of (a,g) reactions involving stable beams are performed in various ways. I have been concentrating on two of them. The first one is studying these reactions in direct kinematics by detecting the produced gamma rays. This is what I did during my thesis to measure the cross section of 7Li(a,g)11B. It has been studied throughout the years for several purposes in nuclear astrophysics. For example, it was postulated it could solve the big bang nucleosynthesis Lithium problem. Nowadays, it is clear it does not.However, this reaction plays a role in the production of Boron during type Ic Supernovae. Another way to study (a,g) reactions is to use inverse kinematics. The idea is to send a heavy element beam on a Helium target. This kind of kinematics allows for the detection, with good efficiency, of the heavy recoil product if the beam that did not interact in the target is properly separated. Recoil mass separators, like St. George, are built for this purpose. St. George will be involved in measuring cross sections of reaction important for the s-process like 16O(a,g)20Ne

Made available in DSpace on 2015-02-24T18:04:02Z (GMT). No. of bitstreams: 1 NelyFS_DISSERT.pdf: 2762669 bytes, checksum: d3dfada1fb5b303580f2869a5876d1bd (MD5) Previous issue date: 2011-04-05
The paper demonstrates how it is organized production chain of natural gas in Rio Grande do Norte and highlights some prospects for this sector. The study is backed by elements to understand the process of innovation as the driving force of capitalist dynamics as well as the features of the Brazilian economy in the years 1990 and 2000 that indicated the development of natural gas production in the energy matrix Brazil. It was found that the state has potiguar possibilities for structuring an energy based on elements from the region and with prospects of becoming self-sufficient in electricity, where natural gas has a share of participation in this segment. The automotive and industrial are the biggest consumers of this input. With emphasis on the textile industry. Signaling to a broad horizon of supply, this sector will depend on their investments in research and Deficient, and the policy adopted by government to develop the consumer market
O trabalho demonstra como est? organizada a cadeia produtiva de g?s natural no Rio Grande do Norte e ressalta algumas perspectivas para este setor. O estudo est? respaldado pelos elementos que permitem compreender o processo de inova??o enquanto for?a motriz da din?mica capitalista, bem como os aspectos que caracterizam a economia brasileira nos anos de 1990 e 2000 e, que sinalizaram para o desenvolvimento da produ??o de g?s natural na matriz energ?tica brasileira. Constatou-se que o estado potiguar tem possibilidades de estruturar uma matriz energ?tica embasada em elementos da pr?pria regi?o e com perspectivas de se tornar auto-suficiente em energia el?trica, onde o g?s natural tem uma parcela de participa??o neste segmento. O setor automotivo e industrial s?o os maiores consumidores desse insumo. Com destaque para a ind?stria t?xtil. Sinalizando para um horizonte amplo de oferta, este setor depender? de investimentos e pesquisas em sua infraestrura, e da pol?tica adotada pelo governo para desenvolver o mercado consumidor

In this thesis, I combined field, greenhouse and common-garden experiments to examine the ecological and evolutionary consequences of plant-herbivore interactions and the genetic architecture of fitness-related traits in the insect-pollinated, self-incompatible, perennial herb Arabidopsis lyrata. More specifically, I examined (1) whether damage to leaves and inflorescences affects plant fitness non-additively, (2) whether trichome production is associated with a cost in terms of reduced tolerance to leaf and inflorescence damage, (3) whether young plant resistance to a specialist insect herbivore varies among populations, and (4) whether the evolution of flowering time, floral display and rosette size is constrained by lack of genetic variation or by genetic correlations among traits. A two-year field experiment in a Swedish population showed that damage to rosette leaves and to inflorescences can affect both current and future plant performance of A. lyrata, and that effects on some fitness components are non-additive. A two-year field experiment in another Swedish population indicated that trichome-producing plants are not less tolerant than glabrous plants to leaf and inflorescence damage. In a greenhouse experiment, acceptability of young plants (5-6 weeks old) to ovipositing females and damage received by Plutella xylostella larvae varied considerably among twelve A. lyrata populations. Both oviposition and leaf damage were positively correlated with rosette size, but trichome density in the trichome-producing morph was apparently too low at this developmental stage to influence resistance to P. xylostella. In a common-garden experiment, flowering time, floral display and rosette size varied among four Scandinavian A. lyrata populations, and displayed significant additive genetic variation in some populations. Yet, strong genetic correlations between flowering start and number of flowers, and between petal length and petal width suggest that these traits may not evolve independently. Taken together, the results indicate the need to consider possible long-term and non-additive effects of herbivore damage to different plant parts, that there is no trade-off between trichome production and tolerance to herbivory, that the importance of morphological defenses against herbivory may change through plant ontogeny, and that considerable genetic variation for traits such as flowering time and floral display can be maintained in natural plant populations.

El virus de la laringotraqueitis infecciosa (VLTI) es responsable de una importante enfermedad respiratoria en aves. La glicoproteína G (gpG) es un factor de virulencia en el VLTI, identificada como una proteína viral de unión a quimioquinas (CKBP) capaz de unirse a quimioquinas de aves y de otras especies modulando su actividad. Esto hace de la gpG una proteína de interés científico y comercial, requiriéndose, por lo tanto, tener suficiente cantidad de proteína disponible para futuros estudios funcionales y estructurales. Se describe un método para la producción de gpG recombinante del VLTI en un biorreactor de tanque agitado, infectando la línea celular de Spodoptera frugiperda Sf-9 con el baculovirus BV-gpG. Para este fin, fue necesario una caracterización previa del crecimiento de las células Sf-9; a su vez, optimizar la producción de gpG a pequeña escala y finalmente, definir parámetros operacionales en el biorreactor Biostat B plus que aseguren un ambiente hidrodinámico adecuado para el crecimiento e infección de las células. Las células Sf-9 mostraron una velocidad específica máxima de crecimiento (µmax) de 0,026/h, un tiempo de doblaje poblacional (TDP) de 27 horas y una densidad celular máxima de 8,7x106 cel/mL. A pequeña escala, la producción de gpG fue mayor al cosechar las células a las 72 horas post infección (hpi) independientemente de la multiplicidad de infección (MOI) empleada en el rango de 1,2 a 20. Una mayor producción de gpG fue obtenida al infectar las células durante la fase de crecimiento exponencial temprana comparada a la fase de crecimiento exponencial tardía. La densidad óptima de infección varió en dependencia del empleo de medio condicionado (2x106 cel/mL) o de medio fresco (7x106 cel/mL). En el manejo del biorreactor, se observó que el empleo de una velocidad de agitación de 170 rpm, una tasa de aireación de 0.04 vvm y un valor de pO2 de 40%, mostraron que las células Sf-9 no fueron sensibles a un estrés de corte de 0.38 N/m2 a un valor de número de Reynolds alto (20x104) en condiciones de aireación por sparger. Una eficiente producción de gpG en 3,5 L de biorreactor fue lograda infectando el cultivo en fase de crecimiento exponencial, a una densidad de 2x106 cel/mL, un MOI de 2 y cosechado a las 72 hpi. Mediante un ELISA sandwich se logró cuantificar el rendimiento volumétrico de gpG his, el cual fue de 3.66 mg/L, lo que representa un aumento de 2 fold comparado a la producción en el matraz. Los resultados demuestran la factibilidad de producir glicoproteína G en células de insecto infectadas con un baculovirus a escala de biorreactor.
Tesis

Alarmins and damage associated molecular pattern (DAMP) are endogenous proteins with distinct and various intracellular roles that when released extracellularly act as startingsignals for inflammatory immune responses. The endogenous protein High mobility group box 1 (HMGB1) acts as a DAMP and has been shown to drive progression of multiple inflammatory and autoimmune diseases. During homeostasis HMGB1 is localized in the nucleus of almost any cell, where its main function is organization of the DNA and regulation of transcription. Upon cell death or immune cell activation HMGB1 can be translocated into the cytoplasm for subsequent release into the extracellular space. Extracellular HMGB1 can act as a DAMP by activating several receptors of the immune system. Recent studies focus on HMGB1 release and functional regulation due to prost-translational modifications (PTMs) on cysteine residues. However, little is known about enzymatic regulation of HMGB1. The aim of this thesis was to investigate the possibility of proteolytic processing of HMGB1 by enzymes, which play a crucial role in inflammatory diseases and their progression. We utilized an in vitro model that mimics natural conditions of the autoimmune disease arthritis. Enzymatic digestion of HMGB1 was performed in kinetics studies using the neutrophilic enzymes cathepsin G, neutrophil Elastase as well as matrix metalloproteinase-3, which is released from tissues at the site of inflammation. We defined that HMGB1 is a novel substrate of all of the tested enzymes. All enzymes induced different cleavage pattern. In conclusion, my findings open up the possibility for future studies involving the observed fragments of HMGB1 and their functional features. It also demonstrated that HMGB1 is affected by protease modifications in a disease relevant environment.

Game theory has become very powerful tool for modelling decision-making situations of rational players. However, practical applications are strongly limited by the size of particular game, which is connected to the computational power of computers nowadays. Aim of this master's thesis is to design and implement a library, which would be able to find correlated equilibria in as complex non-cooperative games as possible.

The ultimate goal of my thesis is to develop a better understanding of the contribution of indirect benefits (i.e. good genes) to the evolution of female mate preferences. It is genetic variance in, and genetic correlations (covariances) among, male sexual displays, female preferences for them, and fitness that in part determine the degree to which females preferring certain male displays over others will gain an indirect benefit by having higher fitness offspring. Recent advances in quantitative genetic theory provide the mathematical means for quantifying the strength of indirect selection for female mate preferences (Kirkpatrick and Hall 2004), at least under certain conditions, but there are few empirical systems for which such data exist (Brooks and Endler 2001; Qvarnström et al. 2006). I have undertaken a classic half-sibling breeding design with the ultimate goal of estimating the specific parameters of this model in a population of the Australian fruit fly Drosophila serrata. The breeding design was performed across two environments - one to which the population was well adapted and a novel environment to which it was not - thereby also providing insight into genotype-by-environment interactions for this suite of traits and their effects on good genes indirect benefits in a novel environment. General insight is also gained into the genetic covariance of male and female fitness and the prevalence of intralocus sexual conflict, the quantitative genetic basis of female mate preferences for multiple male traits, the condition-dependence of these traits, and the genetic association between sexual displays and fitness when mutation-selection balance is inferred. My results advocate caution in the application of existing theory to quantify the strength of indirect selection, suggesting that a good genes process may be fundamentally different when the exaggeration of sexual displays is eventually halted and an equilibrium is reached between opposing selection.

In this dissertation an overview on the real representation of quaternions in distribution theory is given. The density functions of the p-variate and matrix-variate quaternion normal distributions are derived from first principles, while that of the quaternion Wishart distribution is derived from the real associated Wishart distribution via the characteristic function. Applications of this theory in hypothesis testing is presented, and the density function of Wilks's statistic is derived for quaternion Wishart matrices.
Dissertation (MSc)--University of Pretoria, 2011.
Statistics
unrestricted

There is much interest in the protection of the ecosystem within the oil and gas industry. This is particularly significant in the countries of the Middle East where the oil and gas sectors contribute a large part, in some cases all of the country economies. A case study research analysis into the Lean and Green principles of one of the State of Kuwait organisations could offer the country huge potential and could benefit other Arabian Gulf countries. In the chosen country (Kuwait), Kuwait Oil Company (KOC) has no other outlet for its business apart from oil and gas production. It also does not concern itself with other support business that could contribute to Kuwait's economy.

Die rheumatoide Arthritis ist eine chronisch-entzündliche Bindegewebserkrankung mit symmetrischem Befall der Gelenke. Die genaue Ätiologie ist bisher unbekannt. Aktivierte synoviale Fibroblasten sollen durch gesteigerte Adhäsion und Produktion von proinflammatorischen Zytokinen und Matrix-lysierenden Proteasen maßgeblich an der Gelenkdestruktion beteiligt sein. Ziel dieser Arbeit war es, ein neues in-vivo-Knorpeldestruktions-Modell zu etablieren, in welchem unter immunkompetenten Bedingungen, die Invasion und Destruktion von Gelenkknorpel durch die Fibroblasten-Zelllinie LS48 über einen längeren Zeitraum simuliert werden kann. Die am Institut für klinische Immunologie der Medizinischen Fakultät der Universität Leipzig etablierte Zelllinie LS48 wurde in die ipsilateralen Kniegelenke von BALB/c-Mäusen injiziert. Die dadurch induzierte Gewebsdestruktion wurde über zehn Wochen in zweiwöchigem Abstand histopathologisch beurteilt und klassifiziert. Als vergleichende Fibroblasten-Zelllinie wurden nicht-invasive NIH/3T3-Zellen eingesetzt. An Hand der Score-Parameter Zellinvasion, Pannusformation und Knorpeldestruktion wurde eine mäßige bis schwer-wiegende Gewebsdestruktion durch die LS48-Zellen bereits ab der zweiten Untersuchungswoche lichtmikroskopisch nachgewiesen, ohne dass dabei pathologische Effekte in den kontralateralen Kniegelenken aufgetreten sind. Polarisationsmikroskopisch wurden für den Parameter Knorpeldestruktion vergleichbare Ergebnisse erzielt. Damit wurde gezeigt, dass das Modell BALB/c LS48 ein erfolgversprechendes Instrument darstellt, das zur Testung neuer therapeutischer Strategien gegen die Gelenkdestruktion verwendet werden kann. Inwieweit die Auseinandersetzung der LS48-Zellen mit dem spezifischen Immunsystem der BALB/c-Maus Auswirkungen auf den Verlauf der Gewebsdestruktion hat, sollte in weiterführenden Experimenten untersucht werden.

The variety of principal minors of nxn symmetric matrices, denoted Zn, can be described naturally as a projection from the Lagrangian Grassmannian. Moreover, Zn is invariant under the action of a group G C GL(2n) isomorphic to (SL(2)xn) x Sn. One may use this symmetry to study the defining ideal of Zn as a G-module via a coupling of classical representation theory and geometry. The need for the equations in the defining ideal comes from applications in matrix theory, probability theory, spectral graph theory and statistical physics. I describe an irreducible G-module of degree 4 polynomials called the hyperdeterminantal module (which is constructed as the span of the G-orbit of Cayley's hyperdeterminant of format 2 x 2 x 2) and show that it that cuts out Zn set theoretically. This result solves the set-theoretic version of a conjecture of Holtz and Sturmfels and gives a collection of necessary and sufficient conditions for when it is possible for a given vector of length 2n to be the principal minors of a symmetric n x n matrix. In addition to solving the Holtz and Sturmfels conjecture, I study Zn as a prototypical G-variety. As a result, I exhibit the use of and further develop techniques from classical representation theory and geometry for studying G-varieties.

Dissertação mest., Biotecnologia, Universidade do Algarve, 2009
Penicillin G acylase (EC 3.5.1.11) (PGA) hydrolyses penicillin G (PG) producing 6-aminopenicillanic acid (6-APA), an important building block in the synthesis of semi-synthetic antibiotics such as ampicillin and amoxicillin. The synthesis of these antibiotics by PGA is already successfully used in lab and pilot scales and more recently in the synthesis of cefalexin (CEX) at industrial scale. This work characterizes the stability and activity of PGA when immobilized in a polyvinyl alcohol based matrix (Lentikat® liquid), PVA/LL by a new and simple entrapment strategy. The biocatalyst retains from 22 to 66% of its original activity, depending on enzyme load. Hydrolysis and synthesis reactions were tested and the immobilized enzyme can be reused for, at least, 10 consecutive batches without decay of initial activity. The preferential pH and temperature for the hydrolysis of PG are 8 and 37ºC, respectively, it is stable at 4ºC and its half-life, at 25ºC and pH 8 is roughly 8 days. For the synthesis of CEX there was no decay of initial activity for at least 50 hours, at 14ºC and pH 7.2, which indicates a high operational stability. Substrate inhibition by 7-aminodesacetoxicefalosporanic acid (7-ADCA) was observed both for the free and the immobilized enzyme. These forms of enzyme presented synthesis of CEX and hydrolysis of PGM ratio (S/H) of 4.2 and 2.5, respectively. The biocatalyst (PGA_PVA beads) is suitable for the production of cefalexin in industry since it showed a high operational stability, without enzyme leakage during the reaction and between washing steps.

This thesis consists of two main parts. First of all, the condition number of rectangular Vandermonde matrices with nodes on the complex unit circle is studied. The first time quantitative bounds for the extreme singular values are proven in the multivariate setting and when nodes of the Vandermonde matrix form clusters. In the second part, an optimized presentation of the deterministic stability analysis of the subspace method ESPRIT is given and results from the first part are applied.

Thymoquinone (TQ), a volatile oil component of black seed oil (derived from Nigella sativa), has been shown to have various biological effects including disease treatment and prevention. TQ is believed to share similar properties to the benzoquinones already in use as therapeutic drugs. Based on previous reports on the anti-inflammatory properties of black seed oil and TQ, it was originally hypothesized that TQ would inhibit lipopolysaccharide (LPS)-induced cellular sialidase activity in an anti-inflammatory manner. Sialidase activity was tested on live mouse bone marrow derived primary macrophage cells, BMC-2 macrophage cells, human embryonic kidney epithelial (HEK293) cells and human fibroblast cells using an assay that measures the cleavage of the sialidase specific fluorescent substrate 2’-(4-methylumbelliferyl)-α-DN-acetylneuraminic acid (4-MUNANA). The cleavage of 4-MUNANA causes the release of free 4-methylumbelliferone, which fluoresces at 450nm (blue) after excitation at 365nm. Unexpectedly, TQ induced sialidase activation in all three cell lines and wild type primary macrophage cells. TQ was unable to induce sialidase activity in primary macrophage cells isolated from Neu4 knockout mice suggesting that the TQ activates Neu4 sialidase enzyme. TQ-induced sialidase activity in these live cells was found to occur through intermediate GPCR-associated guanine nucleotide Gαi subunit and matrix metalloproteinase 9 (MMP9) by using specific inhibitors. In addition, TQ was found to induce sialidase activity in Toll-like receptor-deficient HEK293 cells. These latter data suggested that TQ may be activating GPCR Gαi and MMP9 signaling associated with Neu4 sialidase independent of TLRs. It is proposed that TQ-induced sialidase activity may activate Toll-like receptors in macrophage cells and the subsequent production of pro-inflammatory cytokines in the absence of LPS. Immunocytochemical staining of BMC-2 cells shows that TQ induced NFκB activation. NFκB activation was confirmed with electrophoretic mobility shift assay (EMSA) and western immunoblotting techniques. Cytokine arrays were used to test the pro-inflammatory cytokine response induced in mice by 5 hour treatment of TQ, compared to LPS. Mice treated with TQ exhibited an increase in IL-1β, IL-6 and TNF-α production, similar to LPS treatment. Taken together, the findings in these studies suggest that TQ is a novel ligand for Neu4 sialidase activation which consequently induces pro-inflammatory cytokine responses.
Thesis (Master, Microbiology & Immunology) -- Queen's University, 2009-04-21 17:38:10.413

Indiana University-Purdue University Indianapolis (IUPUI)
Recent preclinical reports have provided evidence that endothelial colony forming cells (ECFCs), a subset of endothelial progenitor cells, significantly improve vessel formation, largely due to their robust vasculogenic potential. While it has been known that the Rho family GTPase Cdc42 is involved in this ECFC-driven vessel formation process, the effect of extracellular matrix (ECM) stiffness on its activity during vessel formation is largely unknown. Using a fluorescence resonance energy transfer (FRET)-based Cdc42 biosensor, we examined the spatio-temporal activity of Cdc42 of ECFCs in three-dimensional (3D) collagen matrices with varying stiffness. The result revealed that ECFCs exhibited an increase in Cdc42 activity in a soft (150 Pa) matrix, while they were much less responsive in a rigid (1 kPa) matrix. In both soft and rigid matrices, Cdc42 was highly activated near vacuoles. However, its activity is higher in a soft matrix than that in a rigid matrix. The observed Cdc42 activity was closely associated with vacuole formation. Soft matrices induced higher Cdc42 activity and faster vacuole formation than rigid matrices. However, vacuole area is not dependent on the stiffness of matrices. Time courses of Cdc42 activity and vacuole formation data revealed that Cdc42 activity proceeds vacuole formation. Collectively, these results suggest that matrix stiffness is critical in regulating Cdc42 activity in ECFCs and its activation is an important step in early vacuole formation.

Synopsis My research work is focused on: (i) development of novel Fast NMR methods in solution state and their application to metabolomics and small molecules. (ii) NMR based metabolic study of human IVF to assess embryo viability for implantation. The major components of the embryo growth media were identified for evaluating the embryo quality. Described below are the projects carried out towards the dissertation of my PhD. Chapter 1 describes NMR methods which are the foundation stones for new Fast NMR methods developed. Typical 1D and 2D NMR experiments used in metabolomics and statistical methods for analysis are described. A few applications of metabolomics are also covered in the chapter. Chapter 2 describes a new Fast NMR method based on polarization sharing and parallel acquisition using the dual receiver system. The method developed helps in acquiring simultaneously three 2D NMR spectra: 2D [13C-1H] HETCOR, 2D [1H-1H] TOCSY and 2D [13C-1H] HSQC-TOCSY in a single data set. This method achieves a time saving of about two fold. All the experiments are acquired on molecules with natural abundance of 13C. The method was used to assign the side chain atoms (1H and 13C) of two important peptides. i) 12 amino acid residue peptide, which is a part of central linker domain of Human Insulin like Growth Factor Binding Protein-2 known to play a vital role in the IGF system and ii) a 18 amino acid residue peptide which acts as an antimicrobial agent. Chapter 3 describes extension of the Fast NMR method described in chapter 2. The method is combined with G-matrix Fourier Transform NMR spectroscopy. In this method we have acquire simultaneously two 2D NMR experiments and one reduced dimensional 3D experiment. The three experiments are 2D [13C-1H] HETCOR, 2D [1H-1H] TOCSY and GFT (3,2)D [13C-1H] HSQC-TOCSY, which provide complementary information for rapid assignments. GFT (3,2)D [13C-1H] HSQC-TOCSY gives 3D correlations in a 2D manner facilitating high resolution and unambiguous assignments. The experiments were applied for complete assignment of 21 unlabeled metabolite mixtures corresponding to the Innovative Sequential medium (ISM1) used for culturing human embryos for IVF. Further, a 13C multiplicity edition block is added to the method to simplify the resonances assignment in GFT (3,2)D [13C-1H] HSQC-TOCSY. Taken together, experiments provide time gain of order of magnitudes compared to conventional data acquisition. Chapter 4 of the thesis describes a metabolomics study of Human in-vitro fertilization to assess viable embryos of implantation potential using NMR as non-invasive tool. NMR study included the analysis of 127 embryo culture media (Innovative Sequential Media-1) and 29 controls (culture media without embryo) of both day-2 and day-3 transferred. The embryos were divided into 3 categories 1) implanted (successful) 2) transferred not-implanted (unsuccessful) 3) not transferred based on morphological studies. All NMR experiments were acquired with CPMG (T2 filter) incorporated in 1D 1H presaturation pulse scheme. The study was based on estimation of lactate, pyruvate and alanine levels in the embryo culture media (ISM1). The study reveals higher uptake of pyruvate and high pyruvate/alanine ratios in case of implanted embryos compared to one which failed to implant. Present study provides pyruvate/alanine ratio as a biomarker to select the embryos with high implantation potential. The method combined with morphology based assessment or with other biomarkers can be serve as a powerful tool to assess the embryo quality. Chapter 5 describes a novel NMR method for rapid characterization of translation diffusion of molecules in solution either in mixture or pure form. Unlike acquisition of several 2D [13C-1H] HSQC experiments with varying gradients to get diffusion measurement, a single 2D [13C-1H] HSQC is sufficient to measure the diffusion coefficients which is in the linewidths of peaks. The method uses the idea of accordion NMR spectroscopy, wherein gradients are linearly co-incremented with 13C chemical shift evolution period during t1. The methodology speeds up the acquisition by replacing series of 2D [13C-1H] HSQC with single 2D constant time [13C-1H] HSQC. The method was used to monitor the diffusion of metabolites in a time-resolved manner during polymerization of SDS-PAGE gel. Using this method, it was possible to detect the presence of oligomers of diphenylalanine (FF) during its self assembly to form nanotubular structures.

My research work for PhD has focused on: (i) the development and application of new NMR methodologies to solve challenging problems in structural biology and (ii) studying important biological systems to correlate their structural and functional aspects. I have worked on diverse research projects ranging from NMR methodology development to the study of structure and dynamics of protein-based nanotubes. Chapter 1 of my thesis gives brief introduction to bio-molecular NMR spectroscopy and the different biological systems that I have studied. In recent years, several new methods have emerged for rapid NMR data collection. One class of methods is G-matrix Fourier transform (GFT) projection NMR spectroscopy. GFT NMR spectroscopy involves phase sensitive joint sampling of two or more chemical shifts in an indirect dimension of a multidimensional NMR experiment. Chapter 2 describes a new method based on the principle of GFT NMR for increasing further the speed of data collection. In the current implementations of the GFT method, cosine/sine modulation of all chemical shifts involved in the joint sampling are collected and stored as separate FIDs. A post-acquisition data processing step (application of G-matrix) then separates the different inter-modulations of chemical shifts. Thus, joint sampling of K+1 spins results in 2K combination of chemical shifts (also representing 2K projection angles). One limitation of this approach is that even if only a few of the 2K components of the multiplet (or projection angles) is desired, an entire data set containing information for all 2K shift combinations is collected. We have proposed a simple method which releases this restriction and allows one to selectively detect only the desired linear combination of chemical shifts/projection angles out of 2K combinations in a phase sensitive manner. The method involves selecting the appropriate cosine/sine modulations of chemical shifts and forming the desired linear combination by phase cycling of the radiofrequency pulses and receiver. This will benefit applications where only certain linear combination of shifts are desired or/and are sufficient. Further, G-matrix transformation required for forming the linear combination is performed within the pulse sequence. This avoids the need for any post-acquisition data processing. Taken together, this mode of data acquisition will foster new applications in projection NMR spectroscopy for rapid resonance assignment and structure determination. Chapter 3 describes another GFT NMR-based method for rapid estimation of secondary structure in proteins. This involves the detection of specific linear combination of backbone chemical shifts and facilitates a clear separation and estimation of residues in different secondary structures of a given protein. This methodology named as CSSI-PRO (Combination of Shifts for Secondary structure Identification in PROteins), involves detection of specific linear combination of backbone 1Hα and 13C’ chemical shifts in a two dimensional (2D) NMR experiment. Such linear combination of shifts facilitates editing of residue belonging to α-helical/ β-strand regions into distinct spectral regions nearly independent of the amino acid type. This helps in the estimation of overall secondary structure content of the protein. Comparison of the estimated secondary structure content with those obtained from the respective 3D structures and/or the method of Chemical Shift Index (CSI) was carried out for 254 proteins and gives a correlation of more than 90% and an overall RMSD of 6.5%. The method has high sensitivity and data can be acquired in a few minutes. This methodology has several applications such as for high-throughput screening of proteins in structural proteomics and for monitoring conformational changes during protein folding and/or ligand-binding events. Chapter 4 (Part-A and Part-B) describes an area of my research which involves the study of structure and function in the Insulin-like Growth Factor Binding Protein (IGFBP) family. IGFBPs (six in number; IGFBP1-6) belong to the IGF-system, which plays an important role in growth and development of the human body. This system is comprised of the following components: (i) Two peptide hormones, IGF-1 and -2, (ii) type 1 and type 2 IGF receptors, (iii) six IGF-binding proteins (IGFBP; numbered 1-6) and (iv) IGFBP proteases. IGF-1 and -2 are small signalling peptides (~7.5 kDa) that stimulate action by binding to specific cell surface receptors (IGF-1R) evoking subsequent response inside the cell. Six soluble IGF binding proteins, the IGFBPs, which range in 22-31 kDa in size and share overall sequence and structural homology with each other, regulate the activity of the IGFs. IGFBPs bind strongly to IGFs (KD ~ 300-700 pM) to ensure that all the circulating IGF in the blood stream is sequestered and inhibit the action of IGFs by blocking their access to the receptors. Proteolysis of the IGFBPs dissociates IGFs from the complex, enabling them to bind and activate the cell surface receptors. IGFBPs have been recently implicated in different cancers and HIV/AIDS. However, the nature of their interaction with the ligand: IGF-1 or IGF-2 at a molecular level poorly understood. This is due to the difficulty in over-expressing these proteins in large scale and in soluble amounts which is required for structural studies. We have for the first time developed an efficient method for bacterial expression of full-length human IGFBP-2, a 33 kDa system, in soluble (upto 30 mg/ml) and folded form. Using a single step purification protocol, hIGFBP-2 was obtained with >95% purity and structurally characterized using NMR spectroscopy. The protein was found to exist as a monomer at the high concentrations required for structural studies and to exist in a single conformation exhibiting a unique intra-molecular disulfide-bonding pattern. The protein retained full biologic activity as evident from its strong binding to IGF-1 and IGF-2 detected using surface plasmon resonance (SPR). This study represents the first high-yield expression of wild-type recombinant human IGFBP-2 in E. coli and first structural characterization by NMR. Using different NMR methods, we are now in the process of elucidating the 3D structure of this molecule. Chapter 5 (Part-A and Part-B) describes our discovery of nanotubular structures formed by spontaneous self-assembly of a small fragment from the C-terminal domain of hIGFBP-2. The nanotubular structures are several micrometers long and have a uniform outer diameter of ~35 nm. These structures were studied extensively by NMR and other techniques such as TEM, fluorescence and circular dichroism (CD). The water soluble nanotubes form through intermolecular disulphide bonds due to the presence of three cysteines in the polypeptide chain and exhibit enhanced tyrosine fluorescence. Based on different experimental evidences we have proposed a mechanism for the formation of the nanotubes. This was considered as a breakthrough by the journal ChemComm and featured on the cover-page of the journal. An article highlighting the discovery was also published in RSC news. In recent years, a number of novel polypeptide and DNA based nanotubes have been reported. Our study reveals intrinsically fluorescent self-assembling nanotubes made up of disulphide bonds having the following novel properties: (i) their formation/dissociation can be controlled by tuning the redox conditions, (ii) they do not require the support of any additional chemical agent for self-assembly, (iii) they have high stability due to the involvement of covalent interactions, (iv) the monomer is a small polypeptide chain which can be chemically synthesized or produced using simple recombinant methods and (v) they possess high inherent fluorescence and can thus be easily detected against a background of other proteins. In addition, the presence of an RGD motif in this polypeptide fragment offers avenues for novel biomedical applications. The RGD motif is known to be recognized by integrins. The design of such self-assembling polypeptide fragments containing an RGD motif can be utilized to enhance the efficacy of cancer therapeutics. Towards this end, we have investigated the structural basis of formation of these nanotubular structures by NMR spectroscopy and proposed its application for cancer cell imaging.

Seafloor compliance is a non-intrusive geophysical method sensitive to the shear modulus of the sediments below the seafloor. A compliance analysis requires the computation of the frequency dependent transfer function between the vertical stress, produced at the seafloor by the ultra low frequency passive source-infra-gravity waves, and the resulting displacement, related to velocity through the frequency. The displacement of the ocean floor is dependent on the elastic structure of the sediments and the compliance function is tuned to different depths, i.e., a change in the elastic parameters at a given depth is sensed by the compliance function at a particular frequency. In a gas hydrate system, the magnitude of the stiffness is a measure of the quantity of gas hydrates present. Gas hydrates contain immense stores of greenhouse gases making them relevant to climate change science, and represent an important potential alternative source of energy. Bullseye Vent is a gas hydrate system located in an area that has been intensively studied for over 2 decades and research results suggest that this system is evolving over time. A partnership with NEPTUNE Canada allowed for the investigation of this possible evolution. This thesis describes a compliance experiment configured for NEPTUNE Canada’s seafloor observatory and its failure. It also describes the use of 203 days of simultaneously logged pressure and velocity time-series data, measured by a Scripps differential pressure gauge, and a Güralp CMG-1T broadband seismometer on NEPTUNE Canada’s seismic station, respectively, to evaluate variations in sediment stiffness near Bullseye. The evaluation resulted in a (- 4.49 x10-3± 3.52 x 10-3) % change of the transfer function of 3rd October, 2010 and represents a 2.88% decrease in the stiffness of the sediments over the period. This thesis also outlines a new algorithm for calculating the static compliance of isotropic layered sediments.