Inherited metabolic disorders (IMD) form a diverse group of several hundred different diseases with a relatively high cumulative incidence (stated up to 1:600). They are associated with accumulation of the substrates and lack of the products in specific metabolic pathways, which is caused by deficiency of the enzyme or its activator, or dysfunction of the transport protein. However, the underlying cause is at the DNA level. The grounds for different phenotype manifestation in patients with the same genotype are often not known. During my work at the Institute of Inherited Metabolic Disorders, I designed several new methods for the research of IMD and applied them in the patients and their families. I created procedures for the isolation of lysosomal membranes that are used for the research of lysosomal storage disorders and general properties of lysosomes. Next, I introduced several novel assays for determination of the X-inactivation ratio, which led to a significant increase of informative women. Nowadays, we use these methods in heterozygous women with X-linked diseases in order to study the influence of X-inactivation on the manifestation of the diseases. The cases of a girl with mucopolysaccharidosis type II, a girl with OTC deficiency and a family with the mutation in HPRT1 gene are described...

Cette thèse propose une analyse approfondie de la dynamique des changements observés au sein d’une communauté de chasseurs-cueilleurs, les Baka du Gabon. Ce groupe se compose de moins de 1000 individus et parle une langue oubanguienne dans un environnement bantuphone. Une comparaison avec les autres langues du même sous-groupe linguistique met en évidence les spécificités du baka et met au jour des affinités entre cette langue et le monzombo. Ces deux groupes ethnolinguistiques semblent avoir entretenu des relations qui s’inscrivent dans une dynamique d’échange de compétences (chasse-cueillette vs pêche-maîtrise du fer). Ce type de complémentarité se retrouve dans les relations entre les Baka et leurs voisins bantu actuels, dont en particulier les Fang, pour ce qui concerne le Gabon.Le mode de vie des Baka demeure, encore aujourd’hui, largement marqué par la mobilité et la forêt. Toutefois, la sédentarisation imposée par voie gouvernementale, la contigüité avec les Fang de même que l’influence croissante de la mondialisation entraînent des transformations par rapport auxquelles les Baka cherchent à se positionner. Ces dernières touchent la langue (système et utilisation) de même que bon nombre de pratiques socioculturelles (habitat, mobilité, alimentation, subsistance, religion, etc.).La thèse s’efforce d’identifier ces transformations, de les décrire et d’en évaluer l’impact en tenant compte de la diversité des situations. Elle comporte, par ailleurs, une réflexion critique des principes de catégorisation fondée sur l’étude de plusieurs domaines lexicaux (faune, flore, maladie). Certains changements peuvent apparaître en surface sans pour autant remettre en cause, de manière fondamentale, leur attachement à la forêt et à certaines valeurs ancestrales. Toutefois, les différentes pressions exogènes (i.a. sédentarisation, mondialisation) et endogènes (i.a. attitude des individus, transmission) qui déterminent alors le degré d’avancement des différentes transformations, ne doivent pas être sous évaluées en tant qu’elles sont une menace pesant sur la langue, la connaissance de la flore et de la faune et certaines pratiques socioculturelles. / This thesis proposes a detailed analysis on the dynamic of change observed among the Baka from Gabon, a hunter-gatherer community. This group is composed of less than 1000 individuals speaking an Ubangian language inside a Bantu environment. By comparing their language with others from the same linguistic sub-group, some singularities from Baka and some resemblance with the Monzombo sub-group can be seen. These two ethnolinguistic groups, Baka and Monzombo groups, seem to have kept close contact based on skill exchanges (hunting/gathering and fishing/iron skills). This interaction is witnessed in the exchanges the Baka population preserves with their current Bantu neighbors, especially with Fang in Gabon.Nowadays, the Baka way of life is still characterized by their mobility and the forest. Nevertheless, due to a non-migratory lifestyle imposed by the State, the proximity with the Fang group and the growing globalization, dramatic changes are inflicted to the Baka community. Changes at which they are trying to adapt. These constraints do not affect only their language (system and use) but also many sociocultural habits such as settlement, mobility, food and means of support or religion.The aim of this thesis is to identify these ongoing transformations, to describe and to evaluate their impact bearing in mind the singularity of many contexts. An argumentative reflection on categorization principles is also proposed on lexical domains such as fauna, flora and diseases. Certain changes could arise without necessarily questioning their bonds to the forest and ancestral values. Nonetheless, both exogenous (globalization and a sedentary life) and endogenous pressures (individual behavior and culture transmission) determining the progress of different transformations should not be under evaluated as being a threat to the language, to the knowledge of the flora and fauna and to certain sociocultural practices.

Inherited metabolic disorders (IMD) form a diverse group of several hundred different diseases with a relatively high cumulative incidence (stated up to 1:600). They are associated with accumulation of the substrates and lack of the products in specific metabolic pathways, which is caused by deficiency of the enzyme or its activator, or dysfunction of the transport protein. However, the underlying cause is at the DNA level. The grounds for different phenotype manifestation in patients with the same genotype are often not known. During my work at the Institute of Inherited Metabolic Disorders, I designed several new methods for the research of IMD and applied them in the patients and their families. I created procedures for the isolation of lysosomal membranes that are used for the research of lysosomal storage disorders and general properties of lysosomes. Next, I introduced several novel assays for determination of the X-inactivation ratio, which led to a significant increase of informative women. Nowadays, we use these methods in heterozygous women with X-linked diseases in order to study the influence of X-inactivation on the manifestation of the diseases. The cases of a girl with mucopolysaccharidosis type II, a girl with OTC deficiency and a family with the mutation in HPRT1 gene are described...

No description available.

[pt] A Marinha do Brasil presta o seu apoio logístico em cenários, por vezes, inóspitos, a partir de uma rede logística que, na sua origem, formou-se com base em conceitos e necessidades operativas, podendo também conviver com ineficiências e acomodações pela falta de concorrentes. Em 2008, fruto de uma decisão política e estratégica, dentro do contexto das relações internacionais no qual o Brasil está inserido, iniciou-se o processo de aquisição de novos submarinos convencionais (S-BR) e o apoio à elaboração do projeto e construção de um submarino nuclear (SN-BR), que se constitui no mais complexo e significativo projeto conduzido pela Marinha nos últimos tempos. Não obstante a importância desse projeto, estaria a cadeia de suprimento de sobressalentes (CSS) da Marinha pronta para prestar o devido apoio logístico ao novo meio operativo? O atual desenho de rede da Marinha atende as necessidades deste apoio? Qual o atual estágio de desenvolvimento da CSS e como promover uma maior integração dessa rede, com vistas a um melhor gerenciamento? Em meio a poucos estudos sobre o assunto e uma significativa carência de informações, o presente trabalho apresenta respostas a essas e outras questões correlatas, que se mostram cada vez mais prementes, diante da previsão de início dos testes de mar do primeiro submarino já 2017. Indubitavelmente, a Marinha é reconhecida pela sua grande capacidade de organização e pelo comprometimento de seus profissionais, mas serão necessárias algumas ações a mais para vencer este enorme desafio logístico. / [en] The Brazilian Navy provides logistics support in areas, sometimes inhospitable, using a logistics network that, in its origin, was formed on the basis of military concepts and needs, and, sometimes coexisting with inefficiencies and without competitors. In 2008, the result of a political and strategic decision, in a context of international relations in which Brazil is inserted, began the process of acquiring new Brazilian hunter-killer Submarine (SSK) and the support for design and construction of the Brazilian Nuclear-Powered Attack Submarine (SSN), which constitutes the most complex and significant Navy project in recent times. Despite the importance of this project, the Navy spare parts supply chain (SSC) would able to provide the appropriate logistics support for the new submarines? The current Navy network design meets the needs of this support? What is the current development stage of SSC and how to upgrade the integration of this network for improve the SCM? Few studies about this subject exist and a significant lack of information, therefore, this presents answers to these and other related issues that are becoming increasingly pressing, given the early prediction of sea tests of the first SSK submarine in 2017. Undoubtedly, the Navy is known to be a great organizational due to her organizational skills and the commitment of its seamen, but this project will require a little more to overcome this huge logistical challenge.

This study focuses on the semi-subterranean houses in northern Sweden, specifically in the counties Jämtland, Västerbotten and Västernorrland. The semi-subterranean houses were usedby hunter-gatherers and the houses date to the end of the Mesolithic and the Neolithic. In this study two separate types of semi-subterranean houses are being investigated. Both types of semi-subterranean houses are categorized as ‘settlement embankments’ (Sw. boplatsvall). Within the study one type is called ‘embankments of fire-cracked stones’ (Sw. skärvstensvall) which are situated in the interior part of Norrland, and the other type is called ‘embankmentsof gravel/sand’ (Sw. grusvall) which are mainly found in the coastal areas of Norrland. The purpose of this study is to investigate the number of individuals residing within the semi-subterranean houses. Cross-cultural studies based on ethnographic material is used to calculate how many individuals lived in each house. The cross-cultural study of floor area has resulted in a mean of how much space (6.1 m2) a prehistoric human needs in a dwelling. This number is used to calculate the number of individuals that lived in each house based on the size of the floor area. Another purpose of this study is to investigate if there are any differences between the embankments of fire-cracked stone and the embankments of gravel/sand. Are they simply different construction techniques or are there any other differences between them, such as size, social structure and chronology.

The desire to enhance and make ourselves better is not a new one and it has continued to intrigue throughout the ages. Individuals have continued to seek ways to improve and enhance their well-being for example through nutrition, physical exercise, education and so on. Crucial to this improvement of their well-being is improving their ability to remember. Hence, people interested in improving their well-being, are often interested in memory as well. The rationale being that memory is crucial to our well-being. The desire to improve one’s memory then is almost certainly as old as the desire to improve one’s well-being. Traditionally, people have used different means in an attempt to enhance their memories: for example in learning through storytelling, studying, and apprenticeship. In remembering through practices like mnemonics, repetition, singing, and drumming. In retaining, storing and consolidating memories through nutrition and stimulants like coffee to help keep awake; and by external aids like notepads and computers. In forgetting through rituals and rites. Recent scientific advances in biotechnology, nanotechnology, molecular biology, neuroscience, and information technologies, present a wide variety of technologies to enhance many different aspects of human functioning. Thus, some commentators have identified human enhancement as central and one of the most fascinating subject in bioethics in the last two decades. Within, this period, most of the commentators have addressed the Ethical, Social, Legal and Policy (ESLP) issues in human enhancements as a whole as opposed to specific enhancements. However, this is problematic and recently various commentators have found this to be deficient and called for a contextualized case-by-case analysis to human enhancements for example genetic enhancement, moral enhancement, and in my case memory enhancement (ME). The rationale being that the reasons for accepting/rejecting a particular enhancement vary depending on the enhancement itself. Given this enormous variation, moral and legal generalizations about all enhancement processes and technologies are unwise and they should instead be evaluated individually. Taking this as a point of departure, this research will focus specifically on making a case for ME and in doing so assessing the ESLP implications arising from ME. My analysis will draw on the already existing literature for and against enhancement, especially in part two of this thesis; but it will be novel in providing a much more in-depth analysis of ME. From this perspective, I will contribute to the ME debate through two reviews that address the question how we enhance the memory, and through four original papers discussed in part three of this thesis, where I examine and evaluate critically specific ESLP issues that arise with the use of ME. In the conclusion, I will amalgamate all my contribution to the ME debate and suggest the future direction for the ME debate.