In the normal adult human, hemopoiesis appears to be maintained by the simultaneous activity of many stem cell-derived clones. Conversely, most examples of human myeloid malignancies have been shown to represent clonal populations arising as a result of the unregulated expansion of a single transformed hemopoietic stem cell. The limits of the proliferative capacity of normal hemopoietic stem cells in humans and their persistence in hemopoietic malignancies have, however, not been extensively Investigated. One of the most likely reasons for this is the lack, until very recently, of a widely applicable method to analyze the clonality status of human cell populations. Methylation analysis of two polymorphic genes. HPRT and PGK, now allows such studies to be performed in approximately 50 % of females. The possibility that normal human hemopoietic stem cells might have the capacity to mimic the behaviour of some transformed stem cells by generating clones of progeny that could dominate the entire hemopoietic system was then examined. Such a phenomenon has been well documented in animal models of marrow cell transplantation. I therefore undertook an analysis of all allogeneic marrow transplants performed over a 1 to 1-1/2 year period where the genotype of the donor made clonality analysis using the HPRT or PGK systems possible. Using this approach, I obtained evidence in two patients suggesting that a single or, at most, a very small number of normal primitive hemopoietic stem cells were able to reconstitute the hemopoietic system. In one case the data suggested that such reconstitution was likely to have derived from a stem cell with both lymphopoietic and myelopoietic potential. However, in all other cases hemopoiesis in the transplant recipient was found to be polyclonal. Such findings indicate that clonal dominance in the hemopoietic system is not sufficient to infer that a genetically determined neoplastic change has occurred. In addition, these findings have implications for the design of future gene therapy protocols. The same methodology was also applied to investigate the clonality of different hemopoietic cell populations in patients with chronic myelogenous leukemia (CML) and essential thrombocytosis (ET). In both of these myeloproliferative disorders, the neoplastic clone produces terminally differentiated progeny that appear minimally different from normal. Data from the CML studies confirmed the non-clonal nature of the cells emerging in long-term CML marrow cultures. Similarly, patients transplanted with cultured autologous marrow were shown to undergo polyclonal and bcr-negative reconstitution of their hemopoietic system. Analysis of a series of patients with a clinical diagnosis of ET showed that polyclonal hemopoiesis in the presence of an amplified neoplastic clone is not a rare event in this disorder, and that clonality results do not always correlate with other neoplastic markers associated with myeloproliferative diseases in general. Another example of polyclonal hemopoiesis in the presence of an amplified neoplastic clone was demonstrated in a patient with Ph¹-positive ALL whose disease appeared to have originated in a lymphoid-restricted stem cell. The studies described in this thesis reveal a level of complexity of normal and neoplastic stem cell dynamics not previously documented. They highlight the need for more precise information about the molecular basis of regulatory mechanisms that govern hemopoietic cell proliferation and survival at every level of differentiation. Finally they support the accumulating evidence that acquisition of full malignant potential requires several additive genetic changes first postulated many years ago as the somatic mutation theory of carcinogenesis. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

The master's thesis focuses on the study of algorithms dealing with noise separation from musical signal. The first chapter is an introduction into methods which are used for noise removal of the musical signal. Furthermore, this chapter describes theory to the issue, specifically a description of transformations for converting from time to frequency domain, and finally thresholding method of spectral coefficients is explained in detail. The aim of the second chapter is an analysis of the proposed algorithm, which is engaged in testing. From the beginning fast algorithms of gradual transformation are described and then a detailed description of the algorithm as a whole. Later, this chapter deals with the selection of audio recordings and with preparation of these recordings for the actual testing. Finally, testing of audio samples is presented in the third chapter of this thesis. This chapter also concludes comparison of individual transformations, achieved results and review of algorithm.

In Kiruna, a city transformation is taking place as a result of the mining company LKAB's iron ore mining. As the mining goes deeper, the city is affected above ground. The central parts of the city and 33% of the population will, according to the prognosis, be directly affected by the forthcoming urban transformation. The aim of the study is to reach an increased understanding of how individuals who are affected in different ways by urban transformation experience and create meaning in a new situation. The study also aims to investigate whether power dimensions have an impact on sensemaking and how it manifests itself. Furthermore, the study aims to investigate whether it is possible to find any common opinions in the creation of meaning despite the different individual backgrounds and experiences. The study’s results are based on qualitative semi-structured interviews with individuals who are in some way affected by urban transformation. The theoretical framework of the study is based primarily on Weick's theory of sensemaking and then supplemented by a perspective of power since there is a lack of this in Weick's theory usually ignores it. The study also takes into account Gidden's concept of trust and ontological security to be used in the analysis of the study's results. The results of the study show that there are a number of factors that affect an individual's sensemaking. Some of the factors that are important for sensemaking are access to information, the possibility of participation and power in relation to the sense of control. / I Kiruna sker en stadsomvandling till följd av gruvföretaget LKABs malmbrytning. En malmkropp lutar in under staden och i takt med att brytningen går djupare påverkas staden ovan jord. Stadens centrala delar och 33 procent av befolkningen kommer enligt prognosen direkt påverkas av den kommande stadsomvandlingen. Syftet med studien är att nå en ökad förståelse för hur individer som på olika sätt berörs av stadsomvandlingen upplever och skapar mening i en för dem ny situation. Studien syftar även till att undersöka om maktdimensioner har någon inverkan på meningsskapande och hur det i så fall yttrar sig. Vidare syftar studien till att undersöka om det går att finna några gemensamma uppfattningar i meningsskapandet trots individernas olika upplevelser och erfarenheter. Studiens resultat baseras på kvalitativa semistrukturerade intervjuer med individer som på något sätt påverkas av stadsomvandlingen. Studiens teoretiska ramverk utgår främst från Weicks teori om meningsskapande och kompletteras med ett maktperspektiv då teorin vanligtvis bortser från det. Studien tar också hänsyn till Giddens begrepp tillit och ontologisk trygghet vilka används för att analysera studiens resultat. Resultatet av studien visar att det finns ett antal omständigheter som påverkar en individs meningsskapande. Några av omständigheterna som har betydelse för meningsskapandet är tillgången till information, möjligheten till delaktighet samt makt i relation till känslan av kontroll.

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The saturation of markets due to globalization has caused a need for digital evolution of organizations to generate innovative manufacturing practices to assure sustained competitive capabilities. Even though technological capabilities have the impact to generate competitive capabilities strategic implementation is a must for optimal performance. The phenomenon of digital transformation and relating strategic efforts are subject to greatly varying viewpoints which has made it challenging for manufactures to engage with digital transformation. The purpose of the thesis is to decipher the phenomenon digital transformation and to further identify the vital aspects of approaching digital transformation strategies through analysing literature and manufacturing companies. In order to fulfil the purpose of this research project two research questions was formulated: • RQ 1: Which are the crucial aspects of digital transformation? • RQ 2: How should digital transformation strategies be approached? This thesis is a part of digital transformation coordination project which include four industrial partners. The case companies were therefore set before the initiation of this thesis with including work packages. A literature review was performed to generate an understanding of the different viewpoints and to provide the case companies with an academic insight. Empirical findings were established through the gathering of data through observations during project meetings and the through the use of questionnaires. An analysis was conducted by comparing the different datasets. Establishing a frame of reference were vital in understanding the scattered phenomenon of digital transformation. Through identifying the contents of Industry 4.0 subsequent digital transformation and related strategical efforts provided the thesis with a profound theoretical support. The empirical findings provided the thesis with an understanding of how four different manufacturing companies viewed digital transformation. The different state of digital transformations was identified with additions to stating the possibilities and challenges. The crucial aspects of digital transformation were found through analysing the different views and meanings of digital transformation, presenting technology, and organizationally driven digital transformation and finally the fundamental aspects of digital transformation. A sound approach for manufacturers to strategize digital transformation was found through analysing the key factors of digital transformation strategies and the current constraints of digital transformation strategies. Furthermore, a discussion of additional themes which does not apply to the research questions were found to be the cause of digital transformation disparity throughout the case companies and the communication of digital transformation. The crucial aspects of digital transformation are found to be the identification of internal and external company objects that require a holistic, organizational changing continuous process. Which furtherutilizes the potential of novel disruptive technologies to develop novel business practices to generate value and competitive competences. A sound approach towards digital transformation strategies is suggested to be through generating a current state understanding to recognize the appropriate activities that must be performed and understanding the financial aspects of said activities and formulating them in a practical holistic way to assure adequate organizational support. Furthermore, understanding and communicating each strategical phase is vital to assure that the organizational aspects can support the digital transformation.

Suite aux premiers travaux réalisés par Ito, Hayashi, Unimoto et Hashmi à la fin du siècle dernier, de nombreux groupes de recherche à travers le monde ont contribué à l’important développement de la catalyse homogène à l’or. Ce dernier, possédant une activité catalytique unique, donne accès à un bon nombre de nouvelles synthèses de composés, jusque-là inaccessible en utilisant d’autres méthodes.Les ynamides, un sous-groupe d’alcynes hétéro-substitués, sont des intermédiaires de synthèse ayant une réactivité et une stabilité modulable. Ils trouvent leur application dans des réactions telles que les additions, les cycloadditions et les cycloisomérisations.Dans ce manuscrit sont présentés deux travaux impliquant des réactions d’ynamides en présence d’un catalyseur à l’or.1) Réarrangement d’éthers de propargyliques d’ynamides catalysé par l’or (I) : Un accès pratique aux allénamides substitués.Les allénamides sont des composés qui présentent de nombreuses applications, d’où l’engouement présent pour accéder à ces composés. Nous avons montré que des allénamides substitués et fonctionnalisés sont facilement accessibles par une réaction de transfert d’hydrure [1,5] suivi d’une fragmentation, le tout catalysé par de l’or et en utilisant des ynamides comme substrats.Notre méthode est rapide et pratique. En effet, la réaction se fait dans des conditions douces (température ambiante) avec une charge catalytique faible (4 mol% de catalyseur à l’or) et donne d’excellents rendements (jusqu’à 99%). En plus d’une bonne compatibilité fonctionnelle sur le carbone terminal (R1 et R2), notre méthode tolère aussi des substituants azotés variés (R’ et R’’). De plus, d’autres transformations in-situ sur les allénamides formés in-situ ont été effectuées. Quelques composés spiros et diènes interessants ont été obtenus avec des rendements excellents.2) Catalyse duale à l’or : Une synthèse originale de dérivés tertahydroquinolines par un mécanisme formel d’addition [4+2]Bien qu’une vaste majorité de la catalyse à l’or contient une activation du système π d’une liaison multiple par un seul complexe d’or, des innovations récentes mettant en jeu deux atomes d’or sur une seule molécule ont été développées par plusieurs groupes, dont le nôtre.Le cycle catalytique est initié par la formation de l’acétylénure d’or et par la coordination d’un autre complexe d’or de la liaison triple de l’ynamide. Après une attaque nucléophile de l’acétylenure d’or sur l’ynamine, un vinylidène d’or est formé. Ce dernier est piégé par la double liaison, donnant naissance au cycle aromatique. / General introductionSince the pioneering work by Ito, Hayashi, Unimoto and Hashmi in late of last century, homogeneous gold catalysis has witnessed tremendous development by contributions from research groups all over the world. Gold catalysts, possessing unique catalytic reactivity, intrigued a large number of novel approaches to target molecules which cannot be accessed by other methodology. Ynamide, which belongs to a subclass of hetero-substituted alkynes, represents a versatile building block with balanced reactivity and stability and found a series of applications in useful transformations, such as additions, cycloadditions and cycloisomerizations.As part of our ongoing interest in gold catalysis and ynamide chemistry, in this manuscript, two works involving ynamide in the presence of gold catalyst was presented:1). Gold(I)-Catalyzed Rearrangement of Propargyl Ethers of ynamides: A Practical Method for the synthesis of Substituted AllenamidesAllenamides are versatile synthetic building blocks that have seen numerous applications and therefore great efforts have been devoted to the access to such compounds. We have shown that a series of substituted and functionalized allenamides were easily accessible via a gold catalysted 1,5-hydride shift/fragmentation sequence using ynamides as the starting material. Our method is rapid and practical. It can be performed under very mild conditions (room temperature) with low catalyst loading (4% gold catalyst) and gave excellent yields (up to 99% yield). Besides the good functionality compatibility in the carbon terminal (R1 and R2), our method also tolerate variuous Nitrogen substituents (R’ and R’’). Moreover, further transformation using in-situ formed allenamides was achieved. Some interesting spiral and diene compounds were also formed in excellent yield.2). Dual gold catalysis: a unique approach to derived-tetrahydroquinolines by a formal [4+2] pathwayAlthough vast majority of gold catalysis features π-activation of a multiple bond by a single gold complex, recent innovative advance involving two gold centers in one single molecule was disclosed recently by several research groups and also by our group.The catalytic cycle was initiated by the formation of gold acetylide and coordination of another gold complex to the triple bond of ynamide. After nucleophilic attack of gold acetylide onto ynamide, gold vinylidene was generated. The formed gold vinylidene was then trapped by double bond, giving rise to aromatic rings.

While aspect-oriented programming (AOP) addresses the introduction of “aspects” at the code level, we argue that addressing this at the level of software architecture is conceptually and methodologically more adequate, since many aspects, that is, “crosscutting concerns”, are formulated already in the requirements, and therefore can be dealt with in a more controlled manner in the “earlier” phase of software architecture design. We use the precise concept of software architectures organised as diagrams over a category of component specifications, where the architecture semantics are defined as a colimit specification (Fiadeiro and Maibaum, 1992). The diagram structure suggests aspect introduction via an appropriate variant of graph transformation. Singlepushout rewriting in categories of total homomorphisms has already been used previously for different kinds of “enrichment” transformations; we identify “zigzag-path homomorphisms” as producing a category where many practically useful aspect introductions turn out to be such single-pushout transformations, and present the relevant theorems concerning pushout existence and pushout construction. Practical aspect introduction (e.g., privacy) always breaks some properties (e.g., “message can be read in transit”); therefore, aspect introduction transformations cannot be designed to be semantics preserving. Our special categorical setting enables selective reasoning about property preservation in the transformed specifications, and property introduction from the introduced aspects. This method enables us to detect and resolve both conflicts and undesirable emergent behaviors that arise from aspect introduction or interaction. We have developed tool support to introduce and analyze aspects at the system architecture level through zigzag graph transformation. The implementation is based on Hets, an initiative of Mossakowski et al. (2007) and consists of two key parts: the language development and the zigzag transformation. The development of the MFLogic language is based on the specification language Casl (Astesiano et al., 2002) and uses the logic introduced by Fiadeiro and Maibaum (1992). Besides parsing, syntactic and static semantics correctness checking, the language inclusion in Hets opens the door for automatic property preservation analysis and conflict detection. The main contribution of the tool support in Hets is the automatic aspect introduction and the “result architecture” generation by applying our zigzag graph transformation. / Thesis / Doctor of Philosophy (PhD)

Ce mémoire étudie les loisirs à Sherbrooke, à partir de l'impact des changements sociaux, technologiques et économiques, de 1945 à 1970 et aussi la transformation du rapport entre les gens et le loisir suite à ces changements. Dans un premier temps, c'est la situation du loisir prévalent tout juste avant la période concernée qui est présentée. On remarque la prépondérance de loisirs traditionnels, fortement influencé par le passé rural de la population, qui se distingue par un attachement aux valeurs et coutumes du passé. Il y a cependant un début de développement d'un loisir de type urbain qui prend forme, ainsi qu'un engouement de plus en plus marqué pour des activités nouvelles. On voit également l'intérêt marqué des différentes élites quant à ce phénomène et les efforts qu'ils déploient pour régir son essor. Une catégorie sociale en particulier a une relation particulière avec le loisir. La jeunesse ne fait pas que prendre part aux loisirs, mais s'en sert également pour se définir vis-à-vis des générations précédentes en plus de l'utiliser comme moteur de son émancipation.Ce qui ressort clairement c'est l'ampleur de l'implication de la jeunesse dans le domaine du loisir. La portion adulte de la population vit elle aussi d'énormes transformations dans ce domaine. Celles-ci sont dues particulièrement aux changements sociaux et économiques de l'après-guerre ainsi que par l'introduction de nouvelles technologies permettant de nouvelles formes de loisir. L'expansion du réseau routier et l'appropriation de l'automobile amène des modifications dans les relations entre les gens et leur environnement. Le loisir y vit lui aussi des changements profonds tant dans sa nature qu'au niveau de la place qu'il occupe désormais au sein de la société.

The aim of the study was to investigate the impact of the intersection of race, gender and social class on women leaders’ work experience and career progression in order to come up with strategies for gender transformation at leadership level in corporate South Africa. The problem statement of this research study concerns the indication in the annual report of the Commission for Employment Equity (Department of Labour 2012) that there is under-representation of women, especially African and Coloured women, at top management level relative to the economically active population. The Women Empowerment and Gender Equality Bill was published in the Government Gazette No. 37005 of 6 November 2013. This Bill aims to enforce compliance with the stipulated minimum representation of women at senior levels in both the private and public sectors. This study, with its objective of reaching an understanding of the impact of the intersection of race, gender and social class on women’s career progression, is therefore timeous. Getting the perspective of woman CEOs across race and class on how to transform gender at leadership level could add an important voice to transformation and could be of benefit to decision makers in business and in government. Based on this problem statement the following research questions were formulated: - To what extent does the intersection of race, social class and gender impact on women CEOs’ experience in their work roles and career progression? - How might an understanding of women leaders’ experiences in their roles assist with strategies to transform gender at leadership level in corporate South Africa? Qualitative research methodology was chosen as the appropriate methodology and grounded theory was employed. Purposive, snowball and theoretical sampling methods were used to identify fourteen participants (13 CEOs and one chairman).The life story method was employed for in-depth semi-structured interviews from which rich descriptive data was collected and which was analysed using grounded theory. Findings confirmed that the intersection of race, gender, age and class does have an impact on women’s career progression and their life experiences. The dominant social identity was race for blacks and gender whites; class and age were the overlay. In terms of strategies for gender transformation, first-order constructs from the participants were related to abstract second-order constructs from the literature, which led to the formulation of the WHEEL Theoretical Model. The theoretical model is an integration of different elements required for the formulation of strategies for gender transformation at leadership level. The different elements were women themselves; domestic and family support; the organisation; society and government. Despite some limitations that were encountered, the aim of the study was achieved by making a contribution not only to the development of theory related to strategies for gender transformation at leadership level, which other scholars can build from, but also to the gaining of insights into the intersection of multiple social identities and their impact which can be used by business leaders and policymakers to address inequalities in organisations. In addition, this research study made various recommendations for future research / Business Management

The thesis deals with contact manifolds and their groups of transformations and relatedly with contact fibre bundles. We apply the framework of convenient calculus on in finite dimensional smooth manifolds to study the Chern-Weil theory of groups of strict contactomorphisms producing several non-vanishing type results on the cohomology of the classifying spaces of these groups. Moreover, we prove that the space of isocontact embeddings of one contact manifold to another can be given the structure of a smooth manifold and a principal bundle. Using this we describe a particular smooth model of the classifying space for the group Cont+(M; ) of (co-orientation preserving) contactomorphisms of a closed contact manifold (M; ). Lastly, we show that the standard action of the unitary group U(2) on the standard contact 3-sphere S3 induces a homotopy equivalence Cont+(S3; std) ' U(2).