Osteopetrosis is a metabolic bone disease in mammals characterized by a generalized skeletal sclerosis caused by reduced bone resorption. This reduced bone resorption is manifested in afflicted animals by abnormal bone shape, reduced or absent marrow cavities, extramedullary hemopoiesis, abnormal mineral homeostasis and absent or delayed tooth eruption. The available osteopetrotic animal mutations have been a constant source of fruitful investigations concerning the systemic regulation of osteoclastogenesis and bone metabolism. Tooth eruption, on the other hand, is a localized manifestation of the timely activation of bone resorption and bone formation on opposite sides of an erupting tooth. Its rate-limiting step is the speed of bone resorption to form the eruption pathway. In this dissertation, we used two osteopetrotic rat mutations, toothless (tl) and microphthalmia blanc (mib), to investigate the abnormal development of osteoclasts and tooth eruption in mutant rats with an emphasis on the role of systemic and local factors. The significant contributions to this work are listed below. 1. In the toothless rat, a mutation lacking erupted dentition due to severely reduced bone resorption, colony-stimulating factor-1 (CSF-1) promoted tooth eruption but this was delayed compared to normal rats. Eruption was accompanied by changes in the populations of tartrate-resistant acid phosphatase-positive (TRAP+) mononuclear cells in the dental follicle and TRAP+ osteoclasts on adjacent alveolar bone surfaces. These cell populations were dramatically increased in treated mutants compared to untreated tl rats, but the timing of their appearance was delayed compared to normal littermates. This lag in the appearance of osteoclasts and their precursors corresponded to the delay in eruption of first molars in treated tl rats. 2. CSF-1 also accelerated the eruption of molars in normal rats. CSF-1 increased the number of TRAP+ mononuclear cells in the dental follicle and TRAP+ osteoclasts on adjacent alveolar bone surfaces, but had no effect on the timing of their appearance in normal rats. 3. Our data revealed a differential effect on tooth eruption of the growth factors CSF-1 and epidermal growth factor (EGF). CSF-1 accelerated eruption of molars in normal rats, but had no effect on incisor eruption. On the other hand, EGF accelerated incisor eruption; but did not affect molar eruption in normal rats. 4. We have described the mechanism for the transient, mild form of osteopetrosis inherited by mib rats. Mutant animals possess a typical sclerosis at birth, which diminished--but was not resolved--during the first postnatal month. These characteristics are caused by early reductions in osteoclast number and function which improve to normal levels by 4 weeks. Osteoclast numbers were severely reduced in mib rats between birth and 2 weeks, but improved to near normal levels by 4 weeks. Neonatal abnormalities in osteoclast function included reduced staining for the functional enzymes TRAP and TrATPase, decreased levels of mRNA for both TrATPase and CAll, and inability to form a well-developed ruffled border. None of these defects were apparent after the first postnatal month. 5. Finally, we have shown that the dental abnormalities caused by the mild, transient form of osteopetrosis in mib rats are limited to incisor defects and delayed eruption of all teeth. Histologic and radiographic examination of mutant incisors revealed that, contrary to the situation in normal rats, the apex of the incisors of mib rats failed to extend past the first molar region to the third molar. The incisor apex of newborn mib rats was misshaped due to ankylosis of incisor matrices with alveolar bone. This ankylosis was temporary, being resolved by the third postnatal day. The delayed eruption of incisors in mib rats and abnormal shape and occlusion of these teeth in older animals is a consequence of the temporary ankylosis in newborn rats.

Avian leukosis virus (ALV)-induced osteopetrosis is a proliferative disorder of the bone affecting the growth and differentiation of osteoblasts. Osteopetrosis is a polyclonal disease in which cells of the bone contain, on average, multiple viral DNA copies. Osteopetrotic bone is also characterized by the accumulation of unintegrated viral DNA, suggesting an atypical life cycle of the virus in the infected osteoblasts. To better understand virus-host interactions in the induction of osteopetrosis by ALVs, infected chick osteoblast cultures and osteopetrotic bone were examined for aspects of the virus life cycle and effects of infection on osteoblast function. Levels of infection and virus expression were compared in cultured osteoblasts and osteopetrotic bone. Osteopetrotic bone contained higher levels of viral DNA and correspondingly higher levels of viral proteins than infected osteoblast cultures, suggesting a higher viral load in the diseased bone. A significant level of mature Gag protein was present in the bone, suggesting the accumulation of mature virus particles in the diseased bone. It is possible that the accumulation of virus could facilitate the high levels of infection observed in the diseased bone. The mechanism by which unintegrated viral DNA persisted in osteopetrotic bone was investigated by examining the susceptibility of infected osteoblasts to superinfection. The results indicated that, in culture, infected osteoblasts were able to establish interference to superinfection. This suggests that the persistence of unintegrated viral DNA in osteopetrotic bone may not result from the continuing infection of productively infected osteoblasts. The effect of virus infection on osteoblast function was examined in the diseased bone and in osteoblast cultures. In infected chickens, osteoblast activity, as evidenced by the expression of osteoblast phenotypic markers, was increased only in chickens developing severe osteopetrosis. In culture, virus infection had no apparent effect on either the proliferation or differentiation of osteoblasts. This indicates that infection was itself not sufficient to perturb osteoblast function. Furthermore, it suggested that additional components of the bone may be required for ALV infection to induce the abnormal activity of osteoblasts observed in osteopetrosis.

Synapse development and injury-induced reorganization in the nervous system have been extensively characterized morphologically, although, relatively little is known regarding the molecular and biochemical events that underlie these processes. In an attempt to better understand, at the molecular level, the role of the expression of synaptic proteins during synapse establishment and regeneration, this dissertation examines the dynamics of expression of the neuron-specific gene synapsin I during development and in response to selective lesions of the rat central nervous system. Synapsin I is the best characterized member of a family of nerve-terminal specific phosphoproteins implicated in the regulation of neurotransmitter release. During development, the expression of synapsin I correlates temporally and topographically with synapse formation, and recent physiological studies by Lu et al., (1992) have suggested that synapsin I may participate in the functional maturation of synapses. To better understand the temporal relationship between synapsin I gene expression and particular cellular events during development, we have used in situhybridization histochemistry to localize synapsin I mRNA in the rat central and peripheral nervous systems throughout embryonic and postnatal development, and into the adult period. During development, from the earliest embryonic time point examined (E12), the expression of the synapsin I gene was detectable in both the rat central and peripheral nervous systems. While, in general, levels of synapsin I mRNAs were high in utero, synapsin I cDNA probes revealed specific patterns of hybridization in different regions of the embryonic nervous system. To precisely determine the temporal onset of expression of the synapsin I gene during neuronal development, we examined in detail the appearance of synapsin I mRNA during the well characterized postnatal development of the cerebellum and hippocampus. In both regions, the onset of synapsin I gene expression correlated with the period of stem cell commitment to terminal differentiation. In a second phase, in accord with prior analyses, synapsin I gene expression increases to a maximum for a given neuronal population during synapse formation. In the adult rat brain, our data demonstrates a widespread yet regionally variable pattern of expression of synapsin I mRNA similar to that seen at earlier time points, with noteworthy exceptions. The greatest abundance of synapsin I mRNA was found in the pyramidal neurons of the CA3 and CA4 fields of the hippocampus, and in the mitral and internal granular cell layers of the olfactory bulb. Other areas abundant in synapsin I mRNA were the layer n neurons of the piriform and entorhinal cortices, the granule cell neurons of the dentate gyrus, the pyramidal neurons of hippocampal fields CA1 and CA2, and the cells of the parasubiculum. In general, the pattern of expression of synapsin I mRNA paralleled those encoding other synaptic terminal-specific proteins, such as synaptophysin, VAMP-2, and SNAP-25. Then, to determine specifically how synapsin I mRNA levels are related to levels of synapsin I protein in the adult rat brain, we employed in situhybridization histochemistry and immunohistochemistry to examine in detail the local distribution of both synapsin I mRNA and protein in the hippocampus. In short, these data revealed differential levels of expression of synapsin I mRNA and protein within defined synaptic circuits of the rat hippocampus. Based on these data we hypothesized that locally high levels of synapsin I mRNA in neuronal somata may reflect the ability of the nervous system to respond to select enviromental stimuli and/or injury by producing longterm changes in synaptic circuitry. To test this hypothesis and to better understand the regulation and putative role of synapsin I gene expression in the development of functional synapses in the central nervous system, we first examined the developmental pattern of expression of the synapsin I gene; in dentate granule neurons of the dentate gyrus and their accompaning mossy fibers during the main period of synaptogenic differentiation in the rat hippocampus. The results of these studies indicate a significant difference between the temporal expression of synapsin I mRNA in dentate granule cell somata and the appearence of protein in their mossy fiber terminals during the posmatal development of these neurons. Next, to investigate the regulation and putative role of synapsin I gene expression during the restoration of synaptic contacts in the central nervous system, we examined the expression of the synapsin I mRNA and protein following lesions of hippocampal circuitry. These studies show marked changes in the pattern and intensity of synapsin I immunoreactivity in the dendritic fields of dentate granule cell neurons following perforant pathway transection. In contrast, changes in synapsin I mRNA expression in target neurons, and in those neurons responsible for the reinnervation of this region of the hippocampus, were not found to accompany new synapse formation. On a molecular level, both developmental and lesion data suggest that the expression of the synapsin I gene is tightly regulated in the central nervous system, and that considerable changes in synapsin I protein may occur in neurons without concommitant changes in the levels of its mRNA. From a functional standpoint, our results suggest that the appearance of detectable levels of synapsin I protein in developing and sprouting synapses does not reflect simply synaptogenesis, but coincides with the acquisition of function by those central synapses.

Dielektrické materiály jsou použivány v elektronice i v elektrotechnice. Jako jejich základní vlastnost může považovat změnu jejich charakteristik během jejich životnosti. Změny jsou způsobeny namáhaním materiálu vyvolané elektrickými či teplotími vlivy. Možnost jak určit průběh jejich charakteristik v závislosti na čase je měření proudu během aplikování elektrického napětí na materiál. Tyto experimenty vědci z LEMD provaděli ručně, tento postup ale není přílíš učinný pro vysokofrekvenční signály nebo pro experimenty s dlouhou periodou. Hlavním cílem této práce bylo vytvořit aplikaci v LabVIEW k ovládaní měřícího přístroje Keithley (generátor napětí) a k automatickému získavání měřených hodnot v pikoampérech. Tato aplikace nabízí uživateli různé funkce: - Zadání vystupního napětí. - Vyběr typu průběhu. - Definování délky periody. - Ovládaní přístroje. - Měření proudu, ukládaní dat do souboru vhodného pro jiné aplikace (textový soubor). - Analýzu naměřených dat.

Objet d’un intérêt tardif dans la recherche universitaire, la musique noise représente pourtant une forme d’art emblématique de l’underground sonore. Elle porte et cristallise une approche radicale en faisant du bruit sa matière, en se jouant de la forme et du développement, en hybridant ses territoires stylistiques. Les pratiques de jeu ne signent plus la suprématie de l’instrument ni de la composition, mais se placent sous le régime d’une expérimentation ludique et bricoleuse. On n’évalue plus la qualité musicale selon le niveau de compétence technique de l’artiste, tandis que les modalités d’écoute sollicitent de manière spécifique le corps et l’environnement. Les pratiques de production, d’organisation et de diffusion de la musique, empruntes de l’éthos du Do it Yourself (DIY) placent l’autonomie, la polyvalence et l’amateurisme au cœur de ce monde de l’art. A partir d’une approche interdisciplinaire marquée par la musicologie, l’esthétique et les sciences sociales, cette thèse entend questionner, à partir d’analyses musicales, d’archives de presse, d’enquêtes, de cartographies et d’une ethnographie menée au sein de la scène parisienne, comment la musique noise et les pratiques sociales qui l’accompagnent nous interrogent sur nos manières conventionnelles d’appréhender ce qu’est la musique et même une « bonne » musique, la figure du musicien, les intermédiaires artistiques ou la scène du concert, au regard de ce qui semble sans doute constituer un nouveau paradigme contemporain de l’expérimentation. / Although noise music has only recently become an object of interest for academic research, it still represents a form of art emblematic of the underground music scene. It is characterized by a radical approach which implies using noise as work material, playing with form and development, and hybridizing its stylistic territories. This approach is reflected by playing practices in which the emphasis is no longer laid on the supremacy of instruments and composition, but rather on playful and makeshift experimentation. Musical quality is not assessed on the artist’s technical skills anymore, while the listening conditions call for a specific implication of both body and environment. The practices of production, organization, and diffusion of music, borrowing from the éthos of DIY, place autonomy, versatility, and amateurism at the heart of this art world. This PhD research, based on musical analyses, press archives, field surveys, topographies, and an ethnographic study of the Parisian scene, proposes an interdisciplinary approach marked by musicology, aesthetics, and social sciences. Its aim is to question the way noise music and its specific social practices challenge the manner in which we conventionally apprehend what we consider as music, and even “good” music, the image of the musician, the artistic intermediaries or the stage, in light of what seems to constitute a new contemporary paradigm of experimentation.

L'objectif principal de cette thèse de doctorat est de porter un nouveau regard sur le processus de conception architecturale, au travers des cultures constructives, en tissant des liens étroits entre théorie et pratique. Il s'agit de « réhabiliter » la construction au sein du processus de conception architecturale, en tant qu'outil de conceptualisation, au même titre que tout autre fondement du projet. Explorer les conditions d'émergences, symboliques, physiques et matérielles, du projet d'architecture au long d'un cheminement qui relie, pour ne pas dire unifie, sa conception à sa matérialisation, au travers des questions techniques. L'un des objectifs de ce travail de recherche est de proposer un modèle original du processus de conception architecturale, intimement liée aux cultures constructives, autant dans sa signifiance théorique que dans sa pédagogie appliquée. Cette modélisation décrit la manière dont l'esprit d'un architecte praticien conçoit, jusqu'à son édification, un projet d'architecture, en montrant, d'une part comment sa pensée interagit avec les cultures constructives pour conceptualiser ses idées à partir des conditions d'émergence dont il dispose, et d'autre part comment la construction structure sa méthodologie en lui apportant tous les référents iconiques de la matérialité dont elle a besoin, pour atteindre à la matérialisation du projet. Son originalité se situe autant dans l'importance qu'elle donne aux questions constructives que dans la double considération, théorique et pragmatique, qu'elle entretient avec ces questions. Sa spécificité réside quant à elle dans sa dimension cognitive, que sont les modes de pensée des architectes-constructeurs, par rapport à leurs modes d'action / The main goal of this doctoral thesis is to bring a new view on the process of architectural design, through Building cultures, and by evaluating the close links between theory and practice. The purpose is to re-establish the construction within architectural design process, as a conceptualization tool, equally to any other project foundation. Explore conditions of emergence, symbolic, physical or material of the architectural project through the design process, connecting, even unifying, its conceptualization to its embodiment thanks to the technical questions. One of the goal of this work is to propose a pioneering model of architectural conception process, closely linked to building cultures, both in its theoretical means and its applied pedagogy. This modelling describes how the architect- practitioner's mind creates, up to the construction, an architectural project picturing on one side how his mind interacts with building cultures to conceptualize his ideas based on the emergence conditions and on the other side how the construction techniques will structure his methodology by bringing all needed iconic references of the materiality, to finally perform the materialization of the project. Its innovation comes both from the weight of the constructional approach and the dual estimation, theoretical and pragmatic of those topics. Its specificity lies in its cognitive dimension of the thinking of the architect-builders, and how they interact with execution modes

This work assesses the evolution of textile production in the Czech lands during the Eneolithic, a period that is the earliest source of broader archaeological information for the study of textile manufacturing. The basis for the study is provided above all by archaeological finds of textile tools (spindle whorls, weights, spools and awls) that are evaluated within individual archaeological cultures in terms of quantity, shape, size and function, archaeological context and chronological development. This is supplemented by a survey of fragmentary textiles and their imprints dating from the Stone Age in the Czech Republic. Another important source of information is provided by findings from research into Eneolithic pile-dwelling settlements around Alpine lakes that have provided numerous finds of archaeological textiles as well as textile-making tools and tool fragments that have not been found in the Czech lands. An interesting comparative set of artefacts is provided by the objects found in the possession of the mummy of Ötzi dating from the Middle Eneolithic Period. The second part of the work focuses on the experimental testing of several hypotheses formulated on the basis of the study of archaeological materials. The experiments focused on the potential of working bast fibre from trees as an...

La valorisation de résidus agricoles, industriels ou urbains se révèle, à mesure des recherches et des avancées, un recours pertinent aux défis s’imposant à l’industrie de la terre cuite et au domaine de l’habitat. L’incorporation de résidus agricoles à travers des produits conventionnels a permis au long de cette étude une économie de ressource argileuse et d’énergie, tout en améliorant les performances mécaniques et thermiques à la base des matériaux de construction. Des matières végétales ajoutées au mélange argileux de fabrication entrainent une formation de porosité, durant la cuisson des produits, selon la libération d’espaces occupés par les particules, à des températures allant de 200 à 400°C. Les pores en formation adoptent alors les formes et les tailles de particules constitutives, en procurant une maitrise de la microstructure et des propriétés usuelles de la terre cuite. Les résidus agricoles à fines particules se décomposent au sein de la matrice argileuse et procurent, en réduisant la taille moyenne des pores, une amélioration des performances mécaniques de près de 40%. Les matières végétales à particules fibreuses suscitent en revanche une augmentation de l’anisotropie originelle de la microstructure et une amélioration notable de 40% des performances thermiques. La combustion de la matière organique assure, en prime, un apport énergétique au procédé de cuisson s’élevant à 35% des besoins en combustible et compensant un coût d’achat éventuel. L’incorporation de matières végétales au sein des produits de terre cuite apparait comme un succès sur le plan économique, environnemental et technique en raison d’une valorisation matière, entrainant une amélioration des performances usuelles, et d’une valorisation énergétique, accordant une réduction des consommations en gaz et des émissions en dioxyde de carbone. / Waste and biomass valorization appears, on a way of research and advances, as a relevant answer in the challenge offered to the clay bricks industry and housing field. Incorporations of agricultural wastes into clayey ceramic bodies accorded, along those investigations, raw material and energy savings, since improving the mechanical and thermal properties on the basis of every building material. Biomass incorporations amongst argillaceous mixtures induce a porosity formation through the firing process under a release, on a range of temperatures going from 200 to 400°C, of the material spaces previously filled by the organic particles. The porous cavities assume the sizes as well as shapes of the biomass particles and provide a microstructure control affording a functional properties command. The agricultural wastes including thin particles fade out into the clayey bodies and provide, through a median pore size reduction, an improvement of the mechanical strength up to 40%. Crops residues showing fibrous particles induce on the other hand an increase of microstructure and porous network anisotropy, leading to a tremendous improvement of nearly 40% in the insulation behavior. The biomass combustion provides a calorific contribution as well, to the industrial process of firing, surrounding 35% of the usual fuel requirements and supplies an eventual cost of agricultural wastes. Biomass incorporation into clayey ceramic appears as a success on economical, environmental and technical terms, according to the material purpose offering an improvement of the functional performances, and energy purpose assuming a diminution of gas consumptions or a reduction of carbon dioxide release.

Background: The rapidly changing world of digital technologies forces many companies to undertake a digital shift by transforming existing business models into digital business models to achieve sustainable value creation and value capture. Especially, for established companies, that have been successful leaders before the dot-com bubble (1995-2000) and whose business models have been threatened by the emergence of digital technologies, there is a need for a digital shift. We refer to this digitization of business models as digital business model innovation. However, often adoption and implementation of digital technologies require tremendous changes and thus, can be challenging for established companies. Therefore, agile methods and business experimentation have become important strategic elements and are used to generate and test novel business models in a fast manner. We introduce lean startup as an agile method for digital business model innovation, which has proven to be successful in digital entrepreneurship. Thus, it requires further empirical investigation on how to use lean startup in established companies for successful digital business model innovation. Purpose: The purpose of our study is to identify enablers and barriers of lean startup as a tool for digital BMI in established companies. Thus, we propose a framework showing how established companies can be successful in digital business model innovation by using lean startup. Method: We conducted exploratory, qualitative research based on grounded theory following an abductive approach. Using a non-probability, purposive sampling strategy, we gathered our empirical data through ten semi-structured interviews with experts in lean startup and digital business model innovation, working in or with established companies, shifting their business model towards a digital business model. By using grounded analysis, we gained an in-depth understanding of how lean startup is used in practice as well as occurring barriers and enablers for established companies. Conclusion: We emphasize that successful use of lean startup for digital business model innovation is based on an effective (1) lean startup management, appropriate (2) organizational structures, fitting (3) culture, and dedicated (4) corporate governance, which all require and are based on solid (5) methodical competence of the entire organization. Furthermore, (6) external influences such as market conditions, role of competition, or governance rules indirectly affect using lean startup as a tool for digital business model innovation.

In Sweden, it is expected that more than 90% of the population will live in cities by 2040. Therefore, cities have an important role in sustainable development to ensure high quality of life in the face of climate change and social challenges. This thesis uses the framework of Urban Living Labs as a form of experimentation to analyse how evaluation and learning in municipalities take place. Districts identified as sites of experimentation in the six mid-sized municipalities Umeå, Gävle, Jönköping, Borås, Örebro, and Lund are studied using a multiple case study approach. Secondary data is discussed together with findings from interviews. The results show that the aims and challenges of experimentation are similar in all cases. Municipalities aim at increasing their attractivity with these extraordinary districts, but they also contribute to sustainable development through innovation in different sectors (e.g., energy, construction, social life). The importance of structured evaluation for learning is recognized, but only few have (as of now) developed a framework for this. Double-loop learning (or reflectivity) is hinted at in the interviews, but for most projects, it is too early to identify whether it will take place. Experiments are contributing to sustainable development on a larger scale mostly through interactions in networks. Personal Networks, as well as international networks (e.g., initiated by the EU), have a special role as these provide incentives for experimentation, quick informal exchange, as well as spread findings and knowledge to municipalities outside of Sweden.