Environmental assessments and authorisations surrounding project level developments are often made in isolation, without consideration of the regional or strategic context within which individual developments are done. This research investigates the quality of Environmental Management Frameworks (EMF) as strategic environmental instrument. EMF is a unique South African instrument that was first conceptualised in 1989, enacted in 2006 and updated in 2010. EMFs were developed to map environmental sensitivity to aid the screening out of undesired developments in sensitive environments and to minimise unnecessary project level assessments in preferred development areas. EMFs form an important link between environmental assessment (EA) processes and planning strategies such as Spatial Development Frameworks (SDFs) and Integrated Development Plans (IDPs), due to their spatial output of environmental sensitivity maps and their ability to feed strategic assessment processes required by SDFs. They have a legal mandate which ensures their assimilation and use. This research uses a multiple case study approach to review seven EMF documents for their quality. The quality aspects identified are the process, methodology and documentation components, using the printed EMF documentation as primary information source. Quality review criteria were subsequently developed to investigate these inputs, using the legal mandate of EMF as basis. Each case was rated for compliance with the quality criteria using a six–level rating schedule. Further analyses were made by comparing the performance of cases against one another. Public participation emerged as the weakest component of EMF practice, while aspects of sensitivity analysis also performed weaker than other aspects. More focus is required on aligning scales and resolutions of map inputs, mapping methods and general integration of spatial data, especially those of adjoining districts. The need to substantiate a rationale for buffer determination also requires further refinement. The practice of conducting EMF is well established and it can be valuable in sustainable development planning and decisionmaking. Recommendations to enhance the sustainability outcomes and hence effectiveness of this instrument are made, as well as future research objectives for increasing its utility. / Thesis (M. Environmental Management)--North-West University, Potchefstroom Campus, 2011.

abstract: Stromal cell-derived factor-1α (SDF-1α) and its key receptor, CXCR4 are ubiquitously expressed in systems across the body (e.g. liver, skin, lung, etc.). This signaling axis regulates a myriad of physiological processes that range from maintaining of organ homeostasis in adults to, chemotaxis of stem/progenitor and immune cell types after injury. Given its potential role as a therapeutic target for diverse applications, surprisingly little is known about how SDF-1α mediated signaling propagates through native tissues. This limitation ultimately constrains rational design of interventional biomaterials that aim to target the SDF-1α/CXCR4 signaling axis. One application of particular interest is traumatic brain injury (TBI) for which, there are currently no means of targeting the underlying biochemical pathology to improve prognosis. Growing evidence suggests a relationship between SDF-1α/CXCR4 signaling and endogenous neural progenitor/stem cells (NPSC)-mediated regeneration after neural injury. Long-term modulation of the SDF-1α/CXCR4 signaling axis is thus hypothesized as a possible avenue for harnessing and amplifying endogenous regenerative mechanisms after TBI. In order to understand how the SDF-1α/CXCR4 signaling can be modulated in vivo, we first developed and characterized a sustained protein delivery platform in vitro. We were the first, to our knowledge, to demonstrate that protein release profiles from poly(D,L,-lactic-co-glycolic) acid (PLGA) particles can be tuned independent of particle fabrication parameters via centrifugal fractioning. This process of physically separating the particles altered the average diameter of a particle population, which is in turn was correlated to critical release characteristics. Secondly, we demonstrated sustained release of SDF-1α from PLGA/fibrin composites (particles embedded in fibrin) with tunable burst release as a function of fibrin concentration. Finally, we contrasted the spatiotemporal localization of endogenous SDF-1α and CXCR4 expression in response to either bolus or sustained release of exogenous SDF-1α. Sustained release of exogenous SDF-1α induced spatially diffuse endogenous SDF-1/CXCR4 expression relative to bolus SDF-1 administration; however, the observed effects were transient in both cases, persisting only to a maximum of 3 days post injection. These studies will inform future systematic evaluations of strategies that exploit SDF-1α/CXCR4 signaling for diverse applications. / Dissertation/Thesis / Doctoral Dissertation Bioengineering 2016

Submitted by Geyciane Santos (geyciane_thamires@hotmail.com) on 2015-07-23T13:37:24Z No. of bitstreams: 1 Dissertação - Volnei da Silva Klehm.pdf: 16125840 bytes, checksum: c35ee4884abb69923aca15bc534eb348 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-07-23T15:43:55Z (GMT) No. of bitstreams: 1 Dissertação - Volnei da Silva Klehm.pdf: 16125840 bytes, checksum: c35ee4884abb69923aca15bc534eb348 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-07-23T15:41:48Z (GMT) No. of bitstreams: 1 Dissertação - Volnei da Silva Klehm.pdf: 16125840 bytes, checksum: c35ee4884abb69923aca15bc534eb348 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-07-23T15:46:34Z (GMT) No. of bitstreams: 1 Dissertação - Volnei da Silva Klehm.pdf: 16125840 bytes, checksum: c35ee4884abb69923aca15bc534eb348 (MD5) / Made available in DSpace on 2015-07-23T15:46:34Z (GMT). No. of bitstreams: 1 Dissertação - Volnei da Silva Klehm.pdf: 16125840 bytes, checksum: c35ee4884abb69923aca15bc534eb348 (MD5) Previous issue date: 2013-07-10 / Não informada / Naturally, patterns that we wish to recognize occurs in several manners. As example, considering the ordinary human iris, it is often to this pattern to manifest different aspects. When acquired one iris can present, in relation to the original pattern, rotation, translation, lighting distortions or mixed noise. Thus, in some cases, it is necessary to the recognition method to have versatility enough to identify such unexpected forms of pattern occurrences that we wish to recognize. In our particular case, filters for correlation with broader flexibility than the standard SDF and MACE filters, for example, are necessary. A consolidated way to express the variation of a data set can be obtained using the method of Principal Component Analysis (PCA) [1, 2]. The PCA optimally represents a dataset and this fact makes it interesting for combination among ordinary correlation filter design and one possible approach consists of the modification of the design of correlation filters to use principal components as their own detection target. In this dissertation, it is proposed to modify the design of correlation filters SDF and MACE to use Principal Component Analysis to represent the set of occurrences of the pattern of interest. One benefit of this approach resides in the fact that PCA incorporate the changes in the set data providing as a result, more flexible filters. Thus, filters designed in this way would succeed in detecting patterns with small distortions translations and rotations. To validate the proposed method, a recognition system that uses the default human iris was designed and, for this purpose, one consolidate database is used. / Naturalmente, os padrões os quais desejamos reconhecer, ocorrem nas mais diversas formas. Por exemplo, supondo como padrão a íris humana, é natural que este padrão seja adquirido de algumas maneiras possíveis. Quando adquirida a íris pode estar, em relação ao padrão original, com rotação, translação, com efeitos de iluminação ou misturadas a ruídos. Dessa forma, em alguns casos, é necessário que o método de reconhecimento tenha versatilidade suficiente para identificar tais formas não esperadas da ocorrência do padrão os quais desejamos reconhecer. Em nosso caso particular, por exemplo, precisamos de filtros de correlação com flexibilidade mais ampla que os filtros SDF e MACE. Uma forma consolidada de expressar a variação de um conjunto de dados pode ser obtida utilizando-se o método por Análise de Componentes Principais (PCA) [1, 2]. A PCA representa de forma ótima um conjunto de dados e esse fato a torna interessante para combinação com o projeto de filtros e uma possível abordagem consiste em sua modificação para que as próprias componentes principais sejam usadas como padrões alvo. Nesta dissertação, é proposta a modificação do projeto de filtros de correlação SDF e MACE de modo a se utilizar a Análise de Componentes Principais para representar o conjunto das ocorrências do padrão de interesse. Um dos benefícios desta abordagem, reside no fato da PCA incorporar as variações presentes no conjunto de dados proporcionando, como resultado, filtros mais flexíveis. Assim, filtros projetados desta forma teriam sucesso na detecção de padrões com pequenas distorções, translações e rotações. Para validar o método proposto, projetamos um sistema de reconhecimento que utiliza como padrão a íris humana e, para tal, uma base de dados consolidada é utilizada.

De nombreuses thèses de grande qualité ont été rédigées autour de la situation sociale de la personne sans domicile fixe. La présente thèse aborde ce même thème,mais sous un angle singulier. Le raisonnement adopté consiste à établir de quelle façon la personne SDF peut être « inventée » en une figure de l’être au rebut. En perdantson travail, son réseau social et son domicile, le SDF quitte les espaces normés de la société. Il fait toujours partie de la structure sociale, mais relégué au plus bas de celle-ci,comme remisé dans un fond du panier social. C’est dans cet espace (physique et mental) que la société assigne à résidence ce(ux) qu’elle ne veut pas voir. Cette configurationsociale où le SDF peut être traité comme la pièce défectueuse d’une production, l’objet de qualité médiocre qu’on met de côté ou quelque chose de négligeable qu’on jette telun déchet. Le SDF serait condamné au rebut social.J’ai découvert la référence à une figure de l’être au rebut dans un texte de l’écrivain Herman Melville. La nouvelle Bartleby, le scribe est le point de départ de maréflexion sociologique. Le concept d’exclusion sociale me semble insuffisant pour décrire une dynamique de mise au rebut, notamment en raison de son approche binaire(dedans/dehors). Par conséquent, j’ai fait le choix de démarches heuristiques plus en phase avec l’idée de processus d’expulsion d’un lieu de vie sociale, d’une perte progressived’appartenance sociale. Ainsi, les chercheurs initiateurs des concepts de disqualification sociale (Paugam) et de désaffiliation sociale (Castel) m’ont été d’une grande utilité.Le SDF est défini négativement, son acronyme signale la lacune et l’absence. Son identité sociale pâtit d’une altérité négative conférée par le regard stigmatisantdu groupe social dont il est issu. À côté de la figure-repoussoir du SDF, je propose une notion que je nomme figure-rebutoir. Par rebutoir, je veux faire entendre d’abord ladimension de rebut, mais également celle de butoir. Cette figure sociale de l’altérité négative est parfois considérée par le corps social comme une pierre d’achoppement. Ellenous effraie parce qu’elle représente cette humanité détériorée que nous craignons de devenir un jour. En effet, la personne SDF assure parfois la fonction d’épouvantailsocial. Une des particularités de cette thèse réside dans la double origine de ses sources épistémologiques. D’une part, les sociologues m’ont fourni une boîte à outils efficacepour saisir le sens de cette mise au rebut. D’autre part, des écrivains concernés par une question sociale m’ont donné accès à un corpus pratique et opérant. Lesdits romanciersont immergé leur fiction dans un univers social où le personnage-SDF tient une place importante. Ces deux savoirs, sociologique et littéraire, concourent à doter cette thèsed’une épaisseur épistémologique indéniable. En effet, force est de constater que, bien souvent, sociologues et écrivains expriment des points de vue connexes et que leursméthodes respectives sont complémentaires.Le SDF, figure sociale de l’être au rebut ? Mes recherches témoignent de sa mise à l’écart, d’un mépris social à l’encontre de cet homme « domicilié » dansl’espace public, d’un refus de la société de reconnaître que c’est son fonctionnement qui le disqualifie et le désaffilie. La personne SDF est environnée d’objets rebutés : ellerécupère les aliments périmés jetés par les commerces, elle se vêtit de vêtements que les autres ont déjà portés et ne veulent plus, elle se confectionne un abri de fortune avecdes matériaux de récupération, elle gagne quelques pièces de monnaie grâce à la collecte de cannettes de soda ou de métaux. La proximité avec le rebut porte atteinte à sadignité et peut l’assimiler à du rebut humain. En effet, la personne SDF peut devenir personne aux yeux des autres, et dès lors se vivre comme rebut d’elle-même. / The social situation of the homeless person has been the subject of many excellent theses. This thesis deals with the same issue, taken from a different viewpoint.It attempts to show how a homeless person can be “invented” as a scrapheap figure. Without a job, a social network or a home, the homeless person exits the standarddimensions of society. He or she remains a part of the social structure but is relegated to its lowest level, a kind of social bottom of the basket. It is within this physical andmental dimension that society confines those it does not wish to see, in which they can be treated as defective parts of a production system, poor quality items that can be castaside or things of such little value that they can be thrown away like rubbish. In this configuration, the homeless person is condemned to be a social reject.I first discovered a literary reference to a scrapheap figure in a short story by Herman Melville, entitled Bartleby the Scrivener, which became the starting pointfor my sociology study. I do not find the concept of social exclusion sufficient for describing the dynamics of rejection, primarily because it is based on a binary notion ofinside and outside. As a result, I have chosen a heuristic approach that is more in keeping with the idea of a process of expulsion from a social living place, a gradual loss ofsocial affiliation. Thus Paugam and Castel, the researchers who initiated the concepts of social disqualification and social disaffiliation respectively, were very helpful to me.The homeless person is defined in negative terms; the adjective is based on the notion of lack or absence. The person’s social identity suffers from a negativealterity conferred by his/her stigmatisation by the social group from which he/she originates. Together with the idea of the homeless person as a figure of repulsion, I haveput forward the notion of what I call “figure-rebutoir”. “Rebutoir” combines the French words « rebut », meaning reject, scrap, waste, and « butoir » meaning a cut-off point,a strict limit. This is important because the social representation of negative alterity is problematic for society, in that the image of damaged humanity generates fear of whatany one of us could become. Indeed, the homeless person sometimes takes on the role of social scarecrow.One of the original features of this thesis lies in the fact that its epistemological sources are twofold. On one hand, sociologists have provided me with efficienttools for understanding the rejection process and on the other, writers with concern for this social issue have given me access to a practical and effective body of documents.The writers in question are novelists who have set their fiction in a social environment in which the homeless character has an important place. Sociological and literaryknowledge combine to give distinctive epistemological depth to the thesis. We are obliged to recognize the frequent connections between the points of view expressed bysociologists and those put forward by writers and to acknowledge the complementarity of their methods.The homeless person – social figure of the being on the scrapheap? My research shows the alienation and social contempt to which people whose « home » is inpublic space are subjected. It shows that society refuses to recognize that it is its own way of functioning that disqualifies and disaffiliates homeless people. The homelessperson is surrounded by rejected items: expired food products thrown out by shops, clothes worn and no longer wanted by other people, makeshift shelters built with whatevermaterials can be found, a few coins earned from collecting soda cans or metal. Living in such proximity to what has been rejected is damaging for a person’s sense of dignityand can lead to his/her status being assimilated to that

L'objectiu d'aquesta tesi és triple. En primer lloc, contribuïm a aprofundir l'anàlisi de la capacitat del model dels tres factors de Fama i French (1993) per valorar els actius financers a Europa. En segon lloc, estudiem la relació entre els factors de Fama i French (FF) i el risc sistemàtic, i, per tant, en quina mesura _es coherent amb la interpretació del model intertemporal de valoració d'actius, que va més enllà de l'efecte mida i de l'efecte valor comptable-valor de mercat. I, en tercer lloc, tenim com a objectiu mesurar la integració dels mercats d'accions europeus, emmarcada en el procés continu d'alineació institucional i econòmica a Europa. En la literatura empírica de la valoració d'actius, el model dels tres factors ha esdevingut un dels més populars per ajustar segons el risc. No obstant això, fins ara, la majoria de treballs empírics han fet referència a un nombre reduït de mercats, especialment als Estats Units. Perquè el model sigui acceptat com a alternativa vàlida al model de fixació de preus d'actius de capital (CAPM), cal més suport empíric. En aquest treball, fem servir una nova mostra amb una construcció nova dels factors de FF que s'aplica en un conjunt extensiu de països, indústries i regions europees. Els resultats que n'hem obtingut impliquen que el model dels tres factors domina clarament el CAPM en cadascuna de les submostres; tot això a banda que els tests formals indiquen que cap dels models és totalment satisfactori per a la valoració d'actius. A més, documentem que l'ampliació del model de FF amb el factor moment noms millora marginalment la capacitat explicativa quan s'aplica a les rendibilitats de les accions europees.El gran èxit del model dels tres factors de Fama i French també ha generat un debat intens sobre la racionalitat econòmica que hi ha al darrere. Nosaltres hem aprofundit aquesta qüestió estudiant si la mida i la ràtio valor comptable-valor de mercat estan relacionades amb oportunitats futures d'inversió. Ho hem estudiat des de dues perspectives diferents. D'una banda, suposem que els canvis en el conjunt d'oportunitats d'inversió es poden representar mitjançant canvis en la ràtio de creixement macroeconòmic. D'altra banda, vinculem els factors de FF construïts a futures ràtios de creixement del PIB a Europa, i trobem que només la mida sembla que conté alguna informació sobre el creixement macroeconòmic futur. Però, fins i tot aquest efecte de la mida no es manté en les nostres diferents submostres.En un segon pas, relacionem la mida i la ràtio valor comptable-valor de mercat amb canvis en els diferencials dels tipus d'interès per crèdit i per termini. Aquests diferencials de rendiment es reconeixen per la capacitat de marcar les oportunitats d'inversió. Malgrat tot, els nostres resultats indiquen que ni els canvis en el diferencial de crèdit a Europa ni els canvis en el diferencial de termini poden actuar com a punts de vista alternatius subjacents als factors de mida o de valor comptable-valor de mercat. De fet, els resultats empírics que obtenim indiquen que, si augmentem el model dels tres factors amb els canvis en els diferencials de crèdit i de termini, fem incrementar la capacitat de valorar carteres d'accions en tots els àmbits: país, indústria i regió. Per tant, sembla que les variables s'haurien de considerar més com a complementàries que com a substitutives, a diferència dels resultats obtinguts per als Estats Units (vegeu Petkova, 2006; Hahn i Lee, 2006).Finalment, per estudiar el grau d'integració dels mercats d'accions europeus, seguim dues vies relacionades. Primer, mostrem que una versió paneuropea del model dels tres factors és capaç d'explicar una porció considerable de la rendibilitat de les carteres domèstiques. Aquest resultat indica que el model conté informació rellevant per valorar les accions domèstiques. Alhora, el resultat pot implicar que els mercats europeus estan integrats (vegeu Bekaert i Harvey, 1995; Roll i Ross, 1980). En un segon pas, més genèric, fem servir l'esquema del Factor de descompte estocàstic (SDF) per estimar i comparar els nuclis de valoració d'actius domèstics en els diferents mercats europeus. Els resultats indiquen que la quantitat d'informació compartida per aquests nuclis de valoració augmenta significativament en el temps, especialment després de l'arribada de l'euro. Aquest resultat pot servir com a indicador addicional de l'increment del nivell d'integració dels mercats d'accions europeus. / El objetivo de esta tesis es triple. Por una parte, contribuimos a profundizar en el análisis de la capacidad del modelo de 3 Factores de Fama y French (1993) para valorar activos financieros en Europa. En segundo lugar, estudiamos la relación entre los factores de Fama y French y el riesgo sistemático. Y por tanto, en qué medida el modelo 3 Factores es consistente con una interpretación de modelo intertemporal de valoración de activos; que va más allá del efecto tamaño y el efecto valor contable - valor de mercado. En tercer lugar, nuestro objetivo es medir la integración de los mercados de acciones europeos, enmarcada en el continuado proceso de alineamiento institucional y económico en Europa. En la literatura empírica de valoración de activos el modelo de 3 Factores se ha convertido en uno de los más populares para ajustar por riesgo. Sin embargo, hasta la fecha, la mayoría de los trabajos empíricos se han aplicado a un número reducido de mercados, especialmente en los Estados Unidos. Para que el modelo sea aceptado como una alternativa válida al CAPM, se requiere un mayor soporte empírico. En este trabajo utilizamos una nueva muestra, con una nueva construcción de los factores de FF, que se aplica a un extensivo conjunto de países, industrias y regiones europeas. Nuestros resultados implican que en cada una de nuestras sub-muestras, el modelo de 3 Factores claramente domina el CAPM; al margen de que los test formales indiquen que ninguno de los modelos es totalmente satisfactorio para la valoración de activos. También documentamos que la ampliación del modelo de 3 Factores con el factor momento sólo mejora marginalmente la capacidad explicativa cuando se aplica a las rentabilidades de las acciones europeas.El enorme éxito del modelo de 3 Factores de Fama y French ha abierto también un intenso debate sobre la racionalidad económica que existe detrás de los mismos. Nosotros ahondamos en esta discusión estudiando si el tamaño y la ratio valor contable-valor de mercado están relacionados con oportunidades de inversión futuras. Lo estudiamos mediante dos aproximaciones distintas, primero suponemos que los cambios en el conjunto de las oportunidades de inversión pueden representarse mediante cambios en la ratio de crecimiento macroeconómico. Por otra parte, vinculamos los factores de FF construidos a futuras ratios de crecimiento de PIB en Europa, y encontramos que sólo el tamaño parece contener alguna información sobre el crecimiento macroeconómico futuro. Pero, incluso este efecto tamaño, no se mantiene para en nuestras distintas sub-muestras. En un segundo paso, relacionamos el tamaño y la ratio valor contable - valor de mercado con cambios en los diferenciales de los tipos de interés por crédito y plazo. Estos diferenciales de rendimiento están reconocidos por su capacidad para marcar las oportunidades de inversión. Sin embargo, nuestros resultados indican que ni los cambios en el diferencial de crédito en Europa, ni los cambios en el diferencial de plazo, pueden actuar como aproximaciones alternativas subyacentes al los factores de tamaño o valor contable - valor de mercado. De hecho, los resultados empíricos que obtenemos indican que si aumentamos el modelo de 3 Factores con los cambios en los diferenciales de crédito y plazo, incrementa la capacidad de valorar carteras de acciones a todos los niveles: país, industria y región. Por tanto, parecería que las variables deberían de ser consideradas más como complementarias que como substitutivas, a diferencia de los resultados obtenidos para los Estados Unidos (vid Petkova, 2006; Hahn y Lee, 2006).Finalmente, para estudiar el grado de integración de los mercados de acciones europeos seguimos dos vías relacionadas. Primero mostramos que una versión paneuropea del modelo de 3 Factores es capaz de explicar una porción considerable de la rentabilidad de las carteras domesticas. Este resultado indica que el modelo contiene información relevante para valorar acciones domésticas. Al mismo tiempo, el resultado puede implica que los mercados europeos están integrados (vid. Bekaert y Harvey, 1995; Roll y Ross, 1980). En un segundo paso, más genérico, utilizamos el esquema de Factor de Descuento Estocástico (SDF) para estimar y comparar los núcleos de valoración de activos domésticos en los diferentes mercados europeos. Nuestros resultados indican que la cantidad de información compartida por esos núcleos de valoración aumenta significativamente en el tiempo, especialmente después de la llegada del euro. Este resultado puede servir como un indicador adicional del incremento del nivel de integración de los mercados europeos de acciones. / The main purpose of this dissertation is threefold. For one, we aim to shed further light on the general pricing ability of the Fama and French (1993) (FF) three-factor model (3FM) in Europe. For two, we mean to assess whether the FF factors are related to systematic risk and, thus, whether the 3FM is consistent with an intertemporal asset pricing explanation behind the size and book-to-market effects. For three, we endeavor to measure the extent to which European equity markets are integrated. This is motivated by the continuous institutional and economic alignment process in Europe.The 3FM has become one of the most popular models of risk adjustment in the empirical asset pricing literature. However, to date most empirical work has been done for a few selected markets, especially the US. Hence, the 3FM demands more time and further empirical support before it may be accepted as a credible theory-based model to replace the CAPM. We use a fresh holdout sample with newly constructed FF factors for an extensive set of European countries, industries, and regions. Our findings imply that in each of our sub-samples, the 3FM clearly dominates the CAPM, even if formal test statistics imply that neither model is free of mispricing. We also document that augmenting the 3FM by a momentum factor may only marginally help to explain European equity return behavior.The enormous success of the 3FM has also triggered an extensive debate about the economic rationale of the FF factors. We purse this discussion by assessing via two different approaches whether size and book-to-market may be related to time varying investment opportunities. We first assume that changes in the investment opportunity set are summarized by changes in future macroeconomic growth rates. Nevertheless, if we link our newly constructed FF factors to future GDP growth rates in the Eurozone, then we find that only size appears to contain some information on future macroeconomic growth. Yet, not even this finding for the size effect is, admittedly, very persistent across our sub-samples.In a second step, we relate size and book-to-market to changes in European default and term spreads. These yield spreads are generally acknowledged for their ability to track investment opportunities. Our results suggest, however, that neither changes in the European default spread nor changes in the European term spread may proxy for the risk underlying our size and book-to-market factors. In fact, our empirical findings imply that augmenting the 3FM by changes in these yield spreads may notably help to price European equity portfolios at country, industry, and regional level. Hence, it appears that the variables may be considered complements rather than substitutes. This is contrary to US findings (see Petkova, 2006, Hahn and Lee, 2006).Finally, we follow two related approaches to study the degree to which European stock markets are integrated. We first show that a pan-European version of the 3FM is able to explain a considerable proportion of domestic equity portfolio returns. For one, this entails that the model contains valuable information from pricing domestic equity. For two, it may imply that European stock markets are integrate (see Bekaert and Harvey, 1995, Roll and Ross, 1980). In a second and more generic step, we utilize a stochastic discount factor (SDF) framework to estimate and compare domestic pricing kernels across European markets. Our results convey that the amount of information shared by these kernels increases significantly over time, especially after the advent of the euro. This may serve as a further indicator of an increasing European stock market integration.

Thesis (PhD)--University of Stellenbosch, 2001. / ENGLISH ABSTRACT: In this thesis we examine some aspects of automatic face recognition, with specific reference to the eigenface technique. We provide a thorough theoretical analysis of this technique which allows us to explain many of the results reported in the literature. It also suggests that clustering can improve the performance of the system and we provide experimental evidence of this. From the analysis, we also derive an efficient algorithm for updating the eigenfaces. We demonstrate the ability of an eigenface-based system to represent faces efficiently (using at most forty values in our experiments) and also demonstrate our updating algorithm. Since we are concerned with aspects of face recognition, one of the important practical problems is locating the face in a image, subject to distortions such as rotation. We review two well-known methods for locating faces based on the eigenface technique.e These algorithms are computationally expensive, so we illustrate how the Synthetic Discriminant Function can be used to reduce the cost. For our purposes, we propose the concept of a linearly interpolating SDF and we show how this can be used not only to locate the face, but also to estimate the extent of the distortion. We derive conditions which will ensure a SDF is linearly interpolating. We show how many of the more popular SDF-type filters are related to the classic SDF and thus extend our analysis to a wide range of SDF-type filters. Our analysis suggests that by carefully choosing the training set to satisfy our condition, we can significantly reduce the size of the training set required. This is demonstrated by using the equidistributing principle to design a suitable training set for the SDF. All this is illustrated with several examples. Our results with the SDF allow us to construct a two-stage algorithm for locating faces. We use the SDF-type filters to obtain initial estimates of the location and extent of the distortion. This information is then used by one of the more accurate eigenface-based techniques to obtain the final location from a reduced search space. This significantly reduces the computational cost of the process. / AFRIKAANSE OPSOMMING: In hierdie tesis ondersoek ons sommige aspekte van automatiese gesigs- herkenning met spesifieke verwysing na die sogenaamde eigengesig ("eigen- face") tegniek. ‘n Deeglike teoretiese analise van hierdie tegniek stel ons in staat om heelparty van die resultate wat in die literatuur verskyn te verduidelik. Dit bied ook die moontlikheid dat die gedrag van die stelsel sal verbeter as die gesigte in verskillende klasse gegroepeer word. Uit die analise, herlei ons ook ‘n doeltreffende algoritme om die eigegesigte op te dateer. Ons demonstreer die vermoë van die stelsel om gesigte op ‘n doeltreffende manier te beskryf (ons gebruik hoogstens veertig eigegesigte) asook ons opdateringsalgoritme met praktiese voorbeelde. Verder ondersoek ons die belangrike probleem om gesigte in ‘n beeld te vind, veral as rotasie- en skaalveranderinge plaasvind. Ons bespreek twee welbekende algoritmes om gesigte te vind wat op eigengesigte gebaseer is. Hierdie algoritme is baie duur in terme van numerise berekeninge en ons ontwikkel n koste-effektiewe metode wat op die sogenaamde "Synthetic Discriminant Functions" (SDF) gebaseer is. Vir hierdie doel word die begrip van lineêr interpolerende SDF’s ingevoer. Dit stel ons in staat om nie net die gesig te vind nie, maar ook ‘n skatting van sy versteuring te bereken. Voorts kon ons voorwaardes aflei wat verseker dat ‘n SDF lineêr interpolerend is. Aangesien ons aantoon dat baie van die gewilde SDF-tipe filters aan die klassieke SDF verwant is, geld ons resultate vir ‘n hele verskeidenheid SDF- tipe filters. Ons analise toon ook dat ‘n versigtige keuse van die afrigdata mens in staat stel om die grootte van die afrigstel aansienlik te verminder. Dit word duidelik met behulp van die sogenaamde gelykverspreidings beginsel ("equidistributing principle") gedemonstreer. Al hierdie aspekte van die SDF’s word met voorbeelde geïllustreer. Ons resultate met die SDF laat ons toe om ‘n tweestap algoritme vir die vind van ‘n gesig in ‘n beeld te ontwikkel. Ons gebruik eers die SDF-tipe filters om skattings vir die posisie en versteuring van die gesig te kry en dan verfyn ons hierdie skattings deur een van die teknieke wat op eigengesigte gebaseer is te gebruik. Dit lei tot ‘n aansienlike vermindering in die berekeningstyd.

Approved for public release; distribution is unlimited / CyberCIEGE provides an addition to traditional Information Assurance (IA) education in the form of an interactive, entertaining, commercial-grade PC-based computer game. Educational objectives are contained in scenarios that serve to teach particular IA concepts. The details of a scenario are contained in a Scenario Definition File (SDF), which is written in the CyberCIEGE Scenario Definition Language. This language is rich enough to express a range of information security policies and operational data access requirements, resulting in a nearly limitless pool of possible scenarios. This thesis developed a playable scenario illustrating confidentiality protection concepts in an open storage environment modeled after an Air Operations Center. Educational goals include physical protection of high value assets and use of strong authentication policies to protect moderate value assets. The major work of this thesis was designing an SDF to reflect a military information security policy and work flow environment contained in the educational goals. The confirmation of the proper operation of selected aspects of the CyberCIEGE game engine, and the assurance that the SDF confronts the player with the security trade-offs occurred through the application of a testing methodology. The creation of detailed solutions and incorrect gameplay examples constitute this testing process. / Captain, United States Air Force

Le récepteur de chimiokine CXCR7 a été récemment identifié comme liant la chimiokine SDF-1, anciennement considérée comme ligand exclusif du récepteur CXCR4. Ces deux récepteurs sont exprimés majoritairement dans les mêmes types cellulaires et, ainsi, la découverte de CXCR7 incite à réévaluer les effets respectifs de SDF-1 sur CXCR4. Étant donné son rôle dans le cancer, CXCR4 est une cible de choix pour le développement de molécules thérapeutiques. Également, CXCR7 semble être impliqué dans la croissance tumorale. AMD3100, un antagoniste «sélectif» pour CXCR4, est maintenant commercialisé. Cet antagoniste a été identifié comme liant lui aussi CXCR7. De plus, sur CXCR7, l’AMD3100 agit comme agoniste puisqu’il induit le recrutement de la β-arrestine, à l’opposé de son effet sur. En revanche, AMD3100 n’induit pas le recrutement de la β-arrestine à CXCR4. Basé sur ces résultats, il est nécessaire de revoir la sélectivité d’autres antagonistes synthétiques de CXCR4. À l’aide de la technique de BRET (Résonance d’un transfert d’énergie par bioluminescence), nos résultats montrent que le Tc14012, un autre antagoniste synthétique de CXCR4, et structurellement distinct de l’AMD3100, interagit avec CXCR7. Contrairement à CXCR4, les deux antagonistes de CXCR4 agissent comme agonistes sur CXCR7 en induisant le recrutement de la β-arrestine. Nos résultats suggèrent que l’organisation spatiale du corps du récepteur serait responsable de cet effet opposé. En conclusion, AMD3100 et Tc14012 ne sont pas sélectifs pour CXCR4, puisqu’ils interagissent avec CXCR7. Lors du développement de nouvelles molécules synthétiques ciblant CXCR4, il serait alors nécessaire d’en évaluer leur sélectivité, et leurs effets en les testant aussi sur CXCR7. / ASBTRACT SDF-1 was at first thought to exclusively bind CXCR4, but it was subsequently found to also bind to the chemokine receptor CXCR7. CXCR4 is a promising target for drug development due to its role in cancer. AMD3100 is newly commercialised synthetic antagonist of CXCR4. This drug leads to massive release of hematopoietic stem cell into the peripheral blood. It was found that AMD3100 also binds to CXCR7 and acts as an agonist of β-arrestin recruitment to CXCR7. An antagonist of CXCR4 acts as an agonist on CXCR7. Prompted by this observation, we tested whether this might hold true for other CXCR4 antagonist. Tc14012, a peptidomimetic of T140, has been extensively described as a potent CXCR4 antagonist. We find that TC14012 also interacts on CXCR7. Like AMD3100, TC14012 alone induces β-arrestin recruitment to CXCR7. Thus, two structurally unrelated CXCR4 antagonists, AMD3100 and TC14012, are agonists of the CXCR7-arrestin pathway. This suggests distinct activation mechanisms of the arrestin pathway by CXCR4 and CXCR7. The results we obtained using a BRET (Bioluminescence Resonance Energy Transfer)-based arrestin recruitment assay, suggest that the CXCR7 receptor core is responsible for the recruitment of beta-arrestin in response to AMD3100 and TC14012. The finding that both AMD3100 and TC14012 do not only bind CXCR4, but also CXCR7, with opposite effects on arrestin recruitment, is important for the use of the compounds as tools to dissect SDF-1-mediated effects. This may be a general feature of synthetic ligands of the two receptors, with potential consequences for drug development. Key words: Chemokine receptor, CXCR4 and CXCR7, BRET, β-arrestin recruitement, TC14012, AMD3100 and SDF-1.

La régulation de la transcription des gènes par les récepteurs des estrogènes ERα et ERβ joue un rôle important dans la croissance cellulaire et dans le développement du cancer du sein. Une augmentation de l’expression de CXCR4 et de son ligand SDF-1/CXCL12 corrèle avec un phénotype plus agressif du cancer du sein. Ici, nous démontrons un mécanisme de boucle de régulation positive entre la signalisation de CXCR4/SDF-1 et l’activité transcriptionnelle des ERs dans des cellules cancéreuses mammaires. L’activité transcriptionnelle de ER et l’expression de gènes cibles de ER, dont SDF-1 lui-même, sont augmentées dans la lignée cancéreuse mammaire MCF-7 en réponse à SDF-1. Ces effets sont bloqués par l’anti-estrogène fulvestrant et par la délétion de CXCR4. Par ailleurs, l’expression des gènes et la prolifération des cellules cancéreuses mammaires MCF-7 en réponse à l’estrogène sont altérées par l’inhibition de CXCR4. La signalisation par les facteurs de croissance joue un rôle important dans le cancer du sein. La surexpression et la dérégulation de la signalisation par le récepteur à activité tyrosine kinase ErbB2 corrèlent avec un phénotype tumoral mammaire plus agressif et un moins bon pronostic. Cependant, comment la signalisation de ErbB2 et de CXCR4 sont fonctionnellement reliées dans la régulation de la réponse de ER dans les cellules cancéreuses mammaires n’est pas connue. Nous démontrons ici que CXCR4 régule négativement l’expression protéique de ErbB2 et de son partenaire d’interaction ErbB3 ainsi que la phosphorylation de ErbB2. CXCR4 altère l’activation de la voie PI3-K/Akt par le dimère ErbB2/ErbB3 en réponse à héréguline alors qu’en présence de SDF-1, les niveaux d’activation sont récupérés. Nous avons trouvé que héréguline-β promouvoit la phosphorylation de la sérine 339 de CXCR4, un site important pour l’internalisation et la signalisation du récepteur. De plus, le recrutement de ErbB2 à CXCR4 est favorisé par ErbB3 et héréguline-β. L’activité transcriptionnelle ainsi que l’expression des gènes cibles de ER en réponse à l’héréguline sont relevées avec l’expression de CXCR4 et partiellement récupérées avec l’addition de SDF-1. Ces résultats démontrent que le recrutement de CXCR4 à ErbB2 altère la signalisation médiée par ErbB2/ErbB3 ainsi que l’activité hormonale de ER dans des cellules cancéreuses mammaires. Nous travaux ont permis d’identifier et de caractériser l’impact de la signalisation médiée par des récepteurs membranaires sur la réponse transcriptionnelle de ER dans des cellules cancéreuses mammaires. La signalisation membranaire est un facteur pouvant contribuer à la résistance aux thérapies endocriniennes et donc cibler les récepteurs impliqués s’avèrerait utile pour améliorer les traitements existants et mettre au point de nouvelles approches. / Induction of estrogen-regulated gene transcription by estrogen receptors ERα and ERβ plays an important role in breast cancer development and growth. High expression of the chemokine receptor CXCR4 and its ligand CXCL12/SDF-1 has also been correlated with aggressive breast tumor phenotypes. Here, we describe a positive regulatory loop between CXCR4/SDF-1 signaling pathway and ER transcriptional competence in human breast cancer cells. Treatment of breast carcinoma MCF-7 cells with SDF-1 increased ER transcriptional activity and expression of ER target genes, including SDF-1 itself. These effects were blocked by the antiestrogen ICI-182780 and by CXCR4 silencing, and conversely, estrogen-induced gene expression and growth of MCF-7 cells were impaired upon CXCR4 inhibition. Growth factor signaling also plays an important role in breast cancer. Overexpression and deregulated signaling of receptor tyrosine kinase ErbB2 correlate with aggressive breast tumor phenotype and poor outcomes. However, how ErbB2 and CXCR4 signaling is functionally related to regulate ER response in breast cancer cells is not known. Here we show that steady-state levels of ErbB2 and its dimeric partner ErbB3, as well as ErbB2 tyrosine phosphorylation were negatively regulated with the expression of CXCR4. CXCR4 downregulated ErbB2/ErbB3 dimer activation of the PI3-K/Akt pathway in response to ErbB3 ligand heregulin-β, whereas addition of SDF-1 restored activation levels. We found that heregulin-β promoted CXCR4 phosphorylation at serine 339, an important site for CXCR4 internalization and signaling. In addition, ErbB2 recruitment to CXCR4 was enhanced by ErbB3 and heregulin-β. Transcriptional activity and gene expression measurement showed that the hormonal repression of ER was relieved with the expression of CXCR4 and partially recuperated with the addition of SDF-1. Together, these results show that CXCR4 recruitment to ErbB2 alters ErbB2/ErbB3 signaling pathway and downstream regulation of ER hormonal activity in in breast cancer cells. Our work has enabled us to identify and characterize the impact of membrane receptors signaling on ER transcriptionnal response in breast cancer cells. Membrane signaling is one of the factors involved in endocrine therapy resistance and targeting the receptors implicated could be benificial to improve existing treatments and to work on the creation of new ones.

Les chimiokines sont des petites protéines secrétées dont la fonction principale est la stimulation de la migration de cellules immunitaires vers différents organes et tissus. Elles sont souvent impliquées lors des maladies inflammatoires, auto-immunes et des cancers. Ainsi, les chimiokines et leurs récepteurs couplés aux protéines G (RCPG) sont la cible pharmacologique de plusieurs molécules, actuellement testées en essais cliniques. Nous avons pris comme modèle, lors de notre étude, le récepteur atypique CXCR7. Ce récepteur est dit atypique, car il ne signalise pas via la voie classique des protéines G, mais plutôt via la voie de la β-arrestine. CXCR7 est impliqué dans de nombreux cancers, favorise la progression métastatique et est un co-récepteur pour le virus de l’immunodéficience humaine (VIH). Cependant, aucune donnée sur son mode de liaison avec ses ligands CXCL11/ITAC et CXCL12/SDF-1 n’existe à date. Nous pensons que cette information est essentielle pour le développement efficace d’agonistes et d’antagonistes, et nous nous sommes intéressés à identifier les résidus essentiels à la liaison des deux ligands de CXCR7 et à son activation par ces derniers. Pour cela, nous avons créé une série de mutants par substitution ou délétion d’acides aminés de la partie N-terminale, des boucles extracellulaires et des domaines transmembranaires du récepteur. Nous avons testé leur marquage en surface cellulaire par cytométrie en flux, leur liaison des deux ligands par expériences de radio-liaison, et leur capacité à recruter la β-arrestine en réponse aux ligands par essais BRET. Les résultats obtenus ont permis d’identifier des résidus importants à l’interaction des systèmes CXCR7/SDF-1 et CXCR7-ITAC et suggèrent des modes de liaison à CXCR7 différents entre ITAC et SDF-1. Tout comme la liaison d’ITAC à son autre récepteur CXCR3, sa liaison à CXCR7 suivrait le mode conventionnel de liaison en deux étapes des récepteurs de chimiokines. Cependant, la liaison de SDF-1 à CXCR7 suivrait un autre mode de liaison, contrairement à sa liaison à son autre récepteur, CXCR4. / Chemokines are small secreted proteins whose major function is to stimulate the migration of immune cells to different organs and tissues. They are often involved in inflammatory and auto-immune diseases as well as cancers. Thus, chemokines and their G proteins Coupled Receptors (GPCR) are the pharmacological target of multiples molecules, currently tested in clinical trials. The model of our study is the atypical receptor CXCR7. This receptor is called atypical because it doesn’t signalize through the classical G protein pathway but rather signalizes through the β-arrestin pathway. CXCR7 is involved in many cancers, promotes metastatic progression and is a co-receptor for human immunodeficiency virus (HIV). However, there are, to date, no data concerning its binding mode to its ligands CXCL11/ITAC and CXCL12/SDF-1. We think that this information is crucial for the efficient development of agonists and antagonists and thus decided to identify the residus that are important for the binding of the two ligands of CXCR7 to the receptor and its subsequent activation. For that, we created a set of mutants by substitution or deletion of amino acids of the N-terminus, extracellular loops and transmembrane domains of the receptor. We then tested their surface expression by antibody staining and flow cytometry, their binding of the two ligands by binding assays and their capability to recruit β-arrestin in response to the ligands by BRET assays. The results obtained allowed us to identify important residues for the interaction of the systems CXCR7/SDF-1 and CXCR7/ITAC. They also suggest different binding modes of the chemokines ITAC and SDF-1 to CXCR7. Just like the binding of ITAC to its other receptor CXCR3, the binding mode of ITAC to CXCR7 follows the conventional two steps binding model of chemokine receptors. However, the binding of SDF-1 to CXCR7 follows another binding mode than the classical two step model, unlike its binding to its other receptor CXCR4.