Köln, Universiẗat, Diss., 2004.

La téléologie a souvent été associée dans la pensée philosophique morale soit à une forme de déterminisme physique, soit aux théories de l’obligation. Il est pourtant possible de sortir de cette opposition ainsi que des autres antinomies apparentes de la pensée éthique. Le point central de notre travail consiste à fonder la théorie morale sur la relation entre la volonté humaine et le bien et à analyser tous les grands questionnements de l’éthique sous l’angle d’une pensée métaphysique qui cherche à comprendre le mécanisme qui conduit de l’imperfection à l’achèvement en l’appliquant différemment selon les êtres. Ce recentrage nous donne la possibilité de sortir de contradictions qui semblaient indépassables depuis la fixation des termes par la philosophie kantienne, en utilisant à profit certaines avancées de la philosophie analytique contemporaine. En plus des réflexions de cette école, l’outil intellectuel de l’analogie permet de penser le mouvement de perfectionnement en conservant tout à la fois la liberté humaine et la rationalité de l’acte. On peut ainsi légitimement penser concilier normes générales, liberté individuelle et désir humain. Notre approche double de la morale, d’une part par une théorie éthique affirmée, et d’autre part par l’étude détaillée de l’acte humain, permet d’aborder les questions de la motivation humaine et de nous sortir de l’opposition entre subjectivisme et objectivité. Notre point de vue résolument orienté vers la compréhension de la volonté comme désir nous permet de repenser la relation de l’individu à la cité et la continuité entre ses tendances natives et la vie politique. / In moral philosophical thought, teleology has often been associated either with a form of physical determinism or with obligation theories. However, it is possible to escape this opposition, and also the other apparent antinomies of ethical thought. The central point of our work consists in founding moral theory upon the relationship between the human will and the Good, and analysing all the great questions of ethical philosophy from the point of view of a metaphysical thought seeking to comprehend the process which leads from imperfection to achievement, by applying it in different ways, according to each entity. This return to the centre allows us to free ourselves from contradictions which seemed inescapable since the terms were fixed by Kantian philosophy. On the other hand, this work profits from certain advances of contemporary analytical philosophy. In addition to the reflections of this philosophical school, the intellectual tool of analogy allows us to think the movement towards perfection, without compromising either human freedom, or rationality of the action. We may thus reasonably think to reconcile general norms, individual freedom, and human desire. Our double approach of morality, on the one hand by a clear-cut ethical theory, on the other by detailed study of the human action allow us to consider the questions pertaining to human motivation and to escape the opposition between subjectivism and objectivity. Our point of view, firmly turned towards understanding the will as desire, allows us to rethink the relation of the individual towards the state, and the continuity between his native tendencies and political life.

This thesis is divided into two parts; Part I consisting of the theory and Part II the experimental work. Part I is divided into three sections; in Section 1 a summary is given of collision processes and how they have been used to explain various experimental results; this is followed in Section 2 by the author's interpretation of some previous experimental observations; a summary of the wave mechanical theory of collisions is given in Section 3. Part II consists of four sections; In Section 1an outline is given of the various ways of exciting spectra and this is followed by a description of the apparatus used by the author in Section 2; the results of the experiments with hydrogen and oxygen are given in Section 3, and the theoretical interpretation of these; the last Section deals with the experiments carried out with hydrogen and helium, and the facts which may be inferred from these experimental results.

Neste trabalho foi desenvolvida uma nova metodologia de produção de iodo-125, que resultou na primeira produção deste radionuclídeo no Brasil. Cápsulas de alumínio foram projetadas, fabricadas e avaliadas para que suportassem condições de pressão, temperatura e fluxo de nêutrons no reator nuclear IEA-R1 do IPEN sem a ocorrência de liberação de material radioativo. Foram projetados, desenvolvidos e fabricados sistemas de carregamento, descarregamento e recuperação dos gases para a manipulação do gás xenônio e do iodo. Foi desenvolvido um novo método de lavagem da cápsula, para dissolução do iodo-125 adsorvido nas paredes, por meio de imersão em banho ultrassônico. Foram irradiadas três cápsulas no reator nuclear IEA-R1, por um período de aproximadamente 60 h contínuas, a um fluxo de nêutrons de 5,5 x 1013 n cm-2 s-1. Foi produzido um total de 13,53 GBq (365,73 mCi) de iodo-125, e o único contaminante encontrado foi o radionuclídeo iodo-126. Na análise radioquímica, pelo método de cromatografia em papel ascendente, o iodo-125 em solução de NaOH apresentou percentual de iodeto acima de 98%, superior à exigência da farmacopeia americana para soluções de iodo radioativo que é de 95%. Para a análise radionuclídica foi desenvolvida uma fonte planar, a base de resina epoxídica, para a contagem do iodo-125 em detector de germânio de alta pureza. A correlação entre o iodo-125 e o iodo-126 produzido apresentou valores entre 0,5 e 0,7% após um período de decaimento de 10 d, grau de pureza suficiente para a utilização em técnicas de radioimunoensaio. / A new methodology of iodine-125 production was developed in this work, performing the first production of iodine-125 in Brazil. Aluminium capsules were designed, manufactured and evaluated to support condition as pressure, temperature and neutron flux in IEA-R1 Nuclear Reactor without releasing radioactive material into reactor pool. It was designed, developed and manufactured systems to load, unload and recover gases to manipulate the xenon gas and the iodine. A new method of capsule rinsing was developed, to dissolve the iodine-125 adsorbed in the walls, using immersion in ultrasonic bath. Three capsules were irradiated in IEA-R1 Nuclear Reactor for approximately 60 h continuous, at a neutron flux of 5.5 x 1013 n cm-2 s-1. It was produced a total of 13.53 GBq (365.73 mCi) of iodine-125 and the radionuclide iodine-126 was the only contaminant found. In radiochemical analysis, by ascending paper chromatography method, the iodine-125 in NaOH solution presented a percentage over 98%, higher than American pharmacopeia requirements for iodine radioactive solutions which is 95%. A planar source was developed, based on epoxy resin, to iodine-125 radionuclidic analysis in high purity germanium detector. The correlation between iodine-125 and iodine-126 produced showed values between 0.5 and 0.7% after a 10 d decay period, a purity grade enough to apply in radioimmunoassay techniques.

Betalaínas são pigmentos vegetais encontrados em algumas espécies de flores fluorescentes. Betalaínas derivadas de aminocumarinas primárias (cBeets) e carboestiril 124 (csBeet124) foram desenvolvidas em nosso grupo de pesquisa para serem usadas como sondas fluorescentes em aplicações de biologia celular. Esta dissertação de mestrado mostra o efeito da metilação das porções imínicas das cBeets e da csBeet124 sobre as suas cinéticas de hidrólise e propriedades fotofísicas. Os quatro derivados N-metilados foram semissintetizados a partir do acomplamento entre o ácido betalâmico e as aminas secundárias em rendimentos entre 15 − 60%. A N-metilação na porção imínica das betalaínas resultou em um aumento da estabilidade hidrolítica de cerca de 20 vezes, sem afetar drasticamente os perfis de absorção e fluorescência ou os rendimentos quânticos de fluorescência. Os resultados obtidos são importantes na ampliação do conhecimento acerca das relações entre a estrutura e as propriedades de betalaínas em solução aquosa. / Betalains are plant pigments found in some species of fluorescent flowers. Betalains derived from primary aminocoumarins (cBeets) and carbostyril 124 (csBeets124) were developed in our research group to be used as fluorescent cell probes. This dissertation shows the effect of the methylation at the imine portion from cBeets and csBeet124 on their hydrolitic kinetics and photophysical properties. The four N-methylated derivatives were semisynthesized from the coupling between betalamic acid and the secondary amines within 15 − 60% yields. N-methylation at the iminic portion of betalains resulted in a hydrolytic stability increase of about 20-fold without affecting drastically their absorption and fluorescence profiles or fluorescence quantum yield. The results obtained are important to increase the knowledgement about the relationships between structure and properties of betalains in aqueous solution

Betalaínas são pigmentos vegetais encontrados em algumas espécies de flores fluorescentes. Betalaínas derivadas de aminocumarinas primárias (cBeets) e carboestiril 124 (csBeet124) foram desenvolvidas em nosso grupo de pesquisa para serem usadas como sondas fluorescentes em aplicações de biologia celular. Esta dissertação de mestrado mostra o efeito da metilação das porções imínicas das cBeets e da csBeet124 sobre as suas cinéticas de hidrólise e propriedades fotofísicas. Os quatro derivados N-metilados foram semissintetizados a partir do acomplamento entre o ácido betalâmico e as aminas secundárias em rendimentos entre 15 − 60%. A N-metilação na porção imínica das betalaínas resultou em um aumento da estabilidade hidrolítica de cerca de 20 vezes, sem afetar drasticamente os perfis de absorção e fluorescência ou os rendimentos quânticos de fluorescência. Os resultados obtidos são importantes na ampliação do conhecimento acerca das relações entre a estrutura e as propriedades de betalaínas em solução aquosa. / Betalains are plant pigments found in some species of fluorescent flowers. Betalains derived from primary aminocoumarins (cBeets) and carbostyril 124 (csBeets124) were developed in our research group to be used as fluorescent cell probes. This dissertation shows the effect of the methylation at the imine portion from cBeets and csBeet124 on their hydrolitic kinetics and photophysical properties. The four N-methylated derivatives were semisynthesized from the coupling between betalamic acid and the secondary amines within 15 − 60% yields. N-methylation at the iminic portion of betalains resulted in a hydrolytic stability increase of about 20-fold without affecting drastically their absorption and fluorescence profiles or fluorescence quantum yield. The results obtained are important to increase the knowledgement about the relationships between structure and properties of betalains in aqueous solution

La mitochondrie est une organite ayant un rôle central dans le métabolisme énergétique de la cellule. Bien que la mitochondrie exprime son propre génome, plusieurs protéines et ARN non-codants issus du génome nucléaire sont nécessaires à la biogenèse et aux fonctions mitochondriales. Les microARNs (miRNAs) sont de petits ARN non-codants qui s'associent à la protéine Argonaute 2 (Ago2) pour moduler l'expression génique au niveau post-transcriptionnelle par ARN interférence. Classiquement, les miRNAs s’apparient à des sites de liaison complémentaires situés dans le 3’-UTR de l’ARNm cible. Nous faisons l'hypothèse que les miRNAs seraient impliqués dans la communication entre le noyau et la mitochondrie. Notre travail a donc porté sur l’étude du rôle des miRNAs dans le contexte de maladies génétiques caractérisées par une dysfonction mitochondriale. Nous avons choisi d’étudier l’ataxie de Friedreich, la plus fréquente des ataxies héréditaires, qui est causée par un déficit d’expression de la protéine mitochondriale frataxine (FXN). Nous avons montré qu'environ 90% de patients étaient homozygotes pour un haplotype spécifique des variants génétiques du 3'-UTR du gène FXN. Ce résultat a été retrouvé dans deux cohortes de patients indépendantes. Par une combinaison d’approche bioinformatique et d’expériences de co-transfections, nous avons montré que les miRNAs, et en particulier miR-124, ciblent les variants du 3’-UTR. En parallèle, nous avons évalué la possibilité que les miRNAs ciblent directement la mitochondrie. Pour cela, nous avons analysé l’expression des miRNAs dans des fractions d'ARN mitochondriale et cytosolique isolées à partir de mêmes cellules HeLa. Nous avons identifié une signature de 13 miRNAs spécifiquement enrichis dans la fraction d'ARN mitochondriale que nous avons appelé «mitomiRs». Nos prédictions ont révèle des fonctions spécifiques de ces mitomiRs à la mitochondrie, y compris la modulation de l'activité de la chaîne respiratoire. Nous avons également montré une localisation de la protéine Ago2 à l’espace inter-membranaire mitochondriale.Notre travail définit ainsi les miRNAs et Ago2 comme un nouveau niveau de communication entre le noyau et les mitochondries. Nous discutons de la possibilité que la mitochondrie agisse comme acteur du ARN interférence ou plutôt comme organite cible. Notre travail ouvre la voie à un nouveau domaine de recherche, qui pourrait avoir une utilité thérapeutique pour palier les dysfonctions mitochondriales. / Mitochondria are organelles that have a central role in the energetic metabolism of the cell. Although mitochondria express their own genome, they rely on the expression of the nuclear genome for their biogenesis and function. microRNAs (miRNAs) are small non-coding RNAs that associate with Argonaute 2 (Ago2) protein to regulate gene expression post-transcriptionallythrough RNA interference. The ‘classic’ view of RNA interference describes the pairing of miRNAs with complementary binding sites within the 3’untranslated region (3’-UTR) of the target mRNA. We hypothesized that miRNAs might be instrumental to the cross-talk between the nucleus and the mitochondria. In the first part, we assessed the role of miRNAs in the context of a rare genetic disease involving mitochondrial dysfunction. We focused on Friedreich's ataxia, the most frequent of inherited ataxia in Europe, which is caused by reduced expression of the mitochondrial protein frataxin (FXN). Intwo independent cohorts of patients, we discovered that about 90% of patients were homozygous forone specific haplotype of genetic variants of the FXN3'-UTR. By a combination of computational target prediction analysis and co-transfection experiments, we showed that miRNAs, and specifically miR-124, are involved in the regulation of the FXN.We then challenged further the relationship between the miRNAs and mitochondria through questioning their localization at mitochondria. To this end, we studied miRNAs from mitochondrial and cytosolic RNA fractions isolated from the same HeLa cells. We identified a signature of 13 miRNAs specifically enriched in the mitochondrial RNA fraction that we termed ‘mitomiRs’. Through pathway-enrichement analysis, we observed a specific mitochondrial role for mitomiRs, including regulation of ATP synthesis coupled electron trasport. We also provided the evidence of Ago2 protein location inside human mitochondria at the inter-membrane space. Our work sketches miRNAs and Ago2 as a novel layer of the interplay between the nucleus and the mitochondria. We discuss whether mitochondria may be instrumental to RNA interference or a target per se. Our work paves the way to a new field of research, which may unravel therapeutic outcomes to rescue mitochondrial dysfunction.

Sverige har som de flesta känner till ett antal olika monopol. Med monopol menas att detgenom reglering bara är svenska staten som får bedriva verksamhet inom Sveriges gränser.Några av de mest kända monopolen är Systembolaget, Apoteket och Svenska spel. Bolagenägs av staten och bedrivs i aktiebolagsform. Anledningen till att staten har valt att regleravissa branscher är för att kunna styra utbudet i form av kvantitet eller prissättning. Det är enform av skydd för den svenska folkhälsan. Systembolagets monopol är till för att kunnakontrollera användandet av alkohol.Vårt syfte med studien är att studera vilka effekter det kan bli om SOU 2008:124 (En framtidaspelreglering.) genomröstas och träder ikraft 2011-01-01.Studien är skriven ur ett samhällsperspektiv. Det empiriska material som vi valt att samla inkommer att vara i en undersökande form för att finna svar på våra forskningsfrågor samt sehur respondenterna uppfattar situationen med spelrätterna existens eller inte.Vår slutsats blev att de nya aktörerna som kan tänkas etablera sig i Sverige endast kommer attgöra detta för att positionera sig på den svenska marknaden ur ett marknadsföringssyfte.Vidare kommer självklart de bolagen som etablerar sig att följa de svenska lagar ochförordningar som gäller. Detta gäller även de svenska skattesatser och redovisningsregler somgäller. Frågan är om de väljer att göra det eller inte? Svaret kommer att helt och hållet att bliekonomiskt.

R.D. Maurer [and] Melvin A. Herlin. / "June 13, 1949." / Bibliography: p. 5. / Army Signal Corps Contract No. W36-039-sc-32037 Project No. 102B. Dept. of the Army Project No. 3-99-10-022.

MicroRNAs are small non-coding RNA molecules with length of about 22 nt. These molecules participate on regulation of gene expression at the post-transcriptional level. They represent the largest group of regulators in the cell and therefore are also involved in all key processes such as proliferation, differentiation or apoptosis. Moreover, they participate in tumor transformation. These small molecules have a great potential to be diagnostic markers or assist in the treatment and prevention of diseases. This research was focused on the development of isolation method using magnetic particles with subsequent electrochemical detection of microRNA. Optimization steps were performed and then the entire method was successfully applied to real samples of HEK293 cells expressing increased levels of miR-124. The developed method proved to be sufficiently specific and applicable to the analysis of microRNA.