Conselho Nacional de Desenvolvimento Científico e Tecnológico / Esta tese tem como foco os efeitos da desigualdade de renda na saúde bucal e as tendências em desigualdades socioeconômicas em saúde bucal. Qualquer injustiça social, pelo caráter moral é digna de estudo, porém nem toda desigualdade de renda é socialmente injusta. Ela se torna injusta quando as pessoas com menos recursos são aquelas que permitem que as desigualdades econômicas afetem direitos humanos, como o direito a um nível de vida que assegure ao indivíduo e a sua família uma vida saudável. As desigualdades de renda foram estudadas em duas vertentes:a) efeitos contextuais da desigualdade de renda na saúde bucal ; b) tendências na diferença de saúde bucal entre pessoas com maior e menor renda. A primeira parte contém quatro artigos originais que estudaram a associação e os mecanismos contextuais p elos quais a desigualdade de renda afeta a saúde bucal. Para isso, foram utilizados dados do inquérito em saúde bucal SBBrasil de 2002. Os resultados mostraram que: a) a associação entre desigualdade de renda e saúde bucal é mais forte em relação à cárie dental do que outras doenças bucais (e.g. doenças periodontais e maloclusões); b)seus efeitos estão mais fortemente associados à doenças bucais de menor latência; c) os efeitos associados à cárie dental afetam pobres e ricos igualmente; e d) a ausência de políticas públicas parece ser a melhor explicação para os efeitos da excessiva desigualdade de renda no Brasil. Ainda em relação às políticas públicas, foi encontrados que os ricos beneficiam-se mais de políticas públicas municipais do que os pobres. A segunda parte desta tese contém dois artigos originais que descrevem as tendências em saúde bucal e o uso dos serviços odontológicos em grupos de maior e menor renda, no Brasil e na Suécia. Para essas análises, foram usados dados dos inquéritos em saúde bucal no Brasil dos anos de 1986 e 2002, e para Suécia foram obtidos dados do "Swedish Level of Living Survey" para 1968, 1974, 1981, 1991 e 2000. As tendências relacionadas à prevalência de edentulismo mostraram que houve uma redução das desigualdade em percentuais absolutos nos dois países, porém, no Brasil houve um aumento das diferenças quando o desfecho foi a prevalência de nenhum dente perdido. As reduções das disparidades em edentulimo estiveram associadas à presença de uma diferença inicial significativa ,já o aumento das desigualdade na prevalência de nenhum dente perdido esteve relacionado a uma pequena desigualdade no início da coleta de dados. Em relação às desigualdades de uso dos serviços, ressalta-se que o grupo mais pobre permanece utilizando menos os serviços odontológicos em ambos os países e as diferenças continuam significantes através dos tempos. Entretanto, tanto no Brasil como na Suécia, essas diferenças reduziram levemente nas coortes jovens em função do declínio no percentual de pessoas mais ricas que visitam o dentista. Nossos dados permitem concluir que as desigualdades, em saúde bucal, mesmo em países altamente igualitários, como a Suécia. / This thesis focuses on the effect of income distribution on oral health and trends on socioeconomic disparities in oral health. Any social injustice, because of moral issues, is worth studying, though not all inequality of is unfair. Income inequality is unfair when people with less economic resources are penalized with poor health because of their condition of poverty. Unjust societies are those that allow economic inequalities to affect human rights as the right to a standard of living that ensures the individuals and their family a healthy life. Income inequalities were studied in two aspects: a) the contextual effects of income inequality in oral health, and; b) trends in the difference in oral health among people with higher and lower income. The first part contains 4 original articles that studied the association and the contextual mechanism by which income inequality affects oral health. For this we used data of the oral health survey SSBrasil in 2002. The results showed that: a) the association between income inequality and oral health is stronger in relation to dental caries than other oral diseases (e.g. periodontal diseases and malocclusions); b) the effects of inequality of income are more strongly associated with oral diseases of a shorter latency: c) that the effects associated with dental caries affect equally the rich and the poor. The second part of this thesis contains two original articles that described the trends in oral health and in the use of dental services into groups of higher and lower income, in Brazil and Sweden. For this analysis data were obtained from the Brazilian oral health surveys for the year 2002, while for Sweden were used data from the "Swedish Level of Living Survey" for the years 1968, 1974, 1981, 1991 and 2000. Trends in the prevalence of edentulismo showed a reduction in absolute disparities in both countries, but in Brazil trends in the prevalence of "no missing tooth" increased. Reductions in disparities in edentulismo were associated with the presence of a significant initiak difference, while the increase in inequality for outcome "no missing tooth" was related to small inequalities in the begining of data collection. Trends in the use of dental services highlighted that the poorer have been using less the dental services in both countries and the difference remain saignificant over time. however, in Brazil and Sweden, these differences decrease slightly in the cohort of young people because there was a decline in the percentage of rich people who visit the dentist. Our data show that income inequalities in oral health and use of dental serviceshave historically favored the more affluent population even in highly egalitarian countires as Sweden.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, the 5-year survival rate being less than 5%. At the time of diagnosis, 90% of PDACs extend beyond the pancreas and distant metastases are often present. Due to aggressive growth, local expansion and early appearance of metastasis, primary PDAC tumours are local enough for curative surgical resection in only 10–20% of the cases. Adjuvant chemotherapy is indicated in these curative-treated cases, with slight improvement in survival. PDAC is considered to represent a heterogeneous group of biologically and prognostically different malignancies. Characterization of these subgroups is essential and there is an urgent need for more accurate biomarkers and targeted treatments in PDAC. In the current work, we immunohistochemically investigated the expression levels and prognostic values of oxidative stress markers (8-OHdG, Keap1, Prx I, II, III, V and VI), epigenetic histone modifiers (KDM4A, KDM4B, KDM4D and SIRT1–4), and cell-cycle regulators (p16, Rb, CDK4) and DNA-repair enzymes (FEN1 and MGMT) in the cohort of surgically treated PDAC patients. We found that Keap1 expression was associated with better pancreatic cancer-specific survival. Expression of antioxidative peroxiredoxins I, III, V and VI was also connected with a more favourable tumour characteristics and Prx I and VI showed prognostic value. When considering the biology of PDAC, we noticed that pivotal epigenetic regulation also occurred in exocrine pancreatic tissue adjacent to resection margins. Overexpression of the cell-cycle regulator CDK4 and the DNA-repair enzyme FEN1 in the whole population, and elevated expression level of MGMT in the most high-risk patients were connected with worse prognosis. The results of the study can be utilized in the future when individualized therapies are being designed for PDAC patients. Due to occurrence of the epigenetic regulation also in exocrine pancreatic tissue adjacent to resection margins, it could be evaluated in future for routine diagnostics and treatment optimization. The potential role of MGMT in the development of PDAC chemoresistance should be studied in the future. / Tiivistelmä Haiman duktaalinen adenokarsinooma (PDAC) on yksi aggressiivisimmista syöpäsairauksista. Viiden vuoden elossaoloennuste on vain lähellä 5 prosenttia. Diagnoosihetkellä 90% haiman adenokarsinoomista yltää haiman ulkopuolelle ja usein kasvain on jo lähettänyt etäpesäkkeitä. Kasvutaipumuksen sekä metastasoinnin takia kuratiivinen kirurginen hoito on mahdollista vain 10–20% tapauksista. Liitännäissolunsalpaajahoito on aiheellista näissä kuratiivistavoitteisesti hoidetuissa tapauksissa. Kuitenkin vaikutus kokonaiselossaoloaikaan on melko vähäinen. Uusimman tutkimustiedon valossa PDAC:aa pidetäänkin heterogeenisenä ryhmänä biologisesti ja ennusteellisesti erilaisia tautiryhmiä. Näiden tautiryhmien tunteminen ja tunnistaminen riittävän tarkkojen merkkiaineiden avulla olisi ensiarvoisen tärkeää, jotta hoitoja voitaisiin kohdentaa niistä hyötyville potilaille. Väitöskirjatutkimuksessa selvitimme immunohistokemiallisin menetelmin oksidatiivisen stressin merkkiaineiden (8-OHdG, Keap1, Prx I, II, III, V ja VI), epigeneettisten histonimodifikaattorien (KDM4A, KDM4B, KDM4D ja SIRT1–4) sekä solusyklin säätelijöiden (p16, Rb, CDK4) ja DNA-korjausentsyymien (FEN1 ja MGMT) ilmentymistä ja ennusteellista arvoa kirurgisesti hoidetuilla PDAC-potilailla. Tutkimuksessamme totesimme, että kasvainkudoksen Keap1-ilmentymä yhdistyi parempiennusteiseen taudinkuvaan. Antioksidatiivisten peroksiredoksiinien I, III, V ja VI ilmentyminen yhdistyi niin ikään suotuisampaan kasvaimen fenotyyppiin ja Prx I ja VI osoittivat ennusteellista arvoa. Havaitsimme lisäksi, että PDAC:n biologiaan keskeistesti vaikuttavaa epigeneettistä säätelyä tapahtuu myös malignin haimakudoksen viereisessä eksokriinisessä haimakudoksessa. Solusyklin säätelijä CDK4:n ja DNA-korjausentsyymi FEN1:n voimakas ilmentyminen koko tutkimuspopulaatiossa sekä kohonnut MGMT:n ilmentyminen korkeimman riskin potilailla yhdistyivät huonompaan taudin ennusteeseen. Väitöskirjatyön tutkimustuloksia voidaan tulevaisuudessa hyödyntää, kun tutkitaan yksilöllisiä hoitomuotoja PDAC-potilailla. Koska epigeneettistä säätelyä tapahtuu myös syövän viereisessä eksokriinisessa haimakudoksessa, voidaan tulevaisuudessa tämän kudoksen arviointia mahdollisesti käyttää rutiinisti diagnostiikassa sekä hoidon optimoinnissa. MGMT:n mahdollinen rooli PDAC:n kemoresistenssin kehittymisessä tulisi tulevaisuudessa selvittää.

A Neoplasia endócrina múltipla tipo 1 (NEM1; OMIM 131100) é uma síndrome endócrina hereditária, que envolve tumores nas glândulas paratireóides, pâncreas endócrino/duodeno e hipófise. Mutações germinativas no gene supressor de tumor MEN1 são identificadas em aproximadamente 80% dos casos familiais. Os casos restantes podem apresentar grandes deleções no gene MEN1 (raras), não identificáveis ao seqüenciamento direto, ou mutações em outros genes, ainda pouco conhecidos. Recentemente, mutações germinativas em genes que codificam quinases dependentes de ciclinas, como o gene supressor de tumor p27Kip1, foram identificadas em cerca de 1-2% dos pacientes NEM1 sem mutação no gene MEN1. Esses pacientes apresentam uma clínica similar à NEM1, sendo chamada de NEM-like ou NEM4. Estudos in vitro mostraram que a proteína codificada pelo gene MEN1, MENIN, controla a expressão gênica de p27Kip1, indicando que ambos os genes fazem parte da mesma via celular supressora de tumor. Devido à correlação genótipo-fenótipo ser muito fraca nessa síndrome e à grande variabilidade fenotípica encontrada em pacientes com NEM1 (mesmo entre indivíduos/familiares que possuem mesma mutação no gene MEN1), no presente estudo investigamos a hipótese do envolvimento do gene p27Kip1, e de outro gene supressor de tumor recentemente associado com um fenótipo tumores hipofisários famílias, o gene AIP, como possíveis moduladores de fenótipo entre os pacientes com NEM1 de uma extensa família brasileira com a mutação germinativa MEN1 c.308delC e ampla variabilidade fenotípica. Dentre uma série de variáveis clínicas investigadas, observamos um possível papel modulador de fenótipo do gene p27Kip1 nesta família com NEM1. Foi encontrada associação significante entre o genótipo do polimorfismo p.V109G do gene p27Kip1, localizado em um domínio de ligação com a proteína p38 (que é um regulador negativo de p27 por levar à degradação dessa proteína), com os seguintes aspectos clínicos: maior agressividade do tumor hipofisário (macro vs. microadenomas), precocidade no desenvolvimento do tumor pancreático, e presença de carcinóides e metástases nos pacientes analisados (p< 0,05). Não foi observada nenhuma associação do gene AIP e o fenótipo dos pacientes com NEM1. O presente estudo investigou, pela primeira vez, o status germinativo do gene p27Kip1 em pacientes com mutação MEN1 e identificou uma associação significante em relação à susceptibilidade e agressividade dos tumores na coorte estudada / Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumoral syndrome that involves tumors in the parathyroids, anterior pituitary and in the pancreatic islet(s) cells. Germline mutations in the tumor suppressor gene MEN1 are detectable through direct sequencing in the majority (80%) of the patients with familial MEN1. The remaining patients may present large MEN1 gene deletions, not detectable through direct sequencing, or mutations in other genes, so far largely unknown. Recently, rare mutations in genes that encode cyclin-dependent kinases, as p27Kip1, have been reported in approximately 1-2% of the patients without a MEN1 mutation. These patients were reported as presenting a MEN1-like (or the MEN4) syndrome phenotype. In vitro studies have demonstrated that the protein encoded by the MEN1 gene, MENIN, controls the expression of the p27Kip1 gene and, therefore, these two genes seem to act in the same intracellular tumor suppressor pathway. Due to the lack of genotype-phenotype correlation in MEN1 and the large clinical variability usually observed within unrelated patients carrying the same MEN1 mutation, we hypothesized that p27Kip1 (as well as AIP gene, recently associated with familial predisposition to pituitary tumors) may act as phenotypic modifying gene(s) in the MEN1 syndrome. Herein, we analyzed possible correlations between p27Kip1 genotype and a number of clinical features. We identified significant statistic associations between the p.V109G p27Kip1 polymorphism and phenotype manifestations, indicating a potential role of p27Kip1 in modifying MEN1 phenotype, as follows: pituitary tumor size; early development of pancreatic tumors, and presence of carcinoids and metastasis (p< 0,05). In addition, a possible association with the AIP gene was excluded. The present study analyzed, for the first time, the germline status of p27Kip1 gene in MEN1-mutated patients and identified a potential interaction between the genotype of this tumor suppressor gene in regulating susceptibility and the tumor aggressiveness in MEN1 patients

Neste trabalho foi medida a tenacidade à fratura de quatro ligas fundidas com composição química base do aço AISI M2 – uma de composição química convencional (liga I), e as demais modificadas por adições de nitrogênio (liga II), cério (liga III) e antimônio (liga IV) – submetidas a tratamentos térmicos visando a decomposição do carboneto M2C, a esferoidização e engrossamento dos carbonetos produto M6C e MC, em altas temperaturas e por diversos tempos. A metodologia empregada nesta avaliação da tenacidade à fratura foi a dos corpos de prova curtos com entalhe chevron segundo ASTM E 1304-97, de forma a superar a necessidade do pré-trincamento por fadiga, procedimento de difícil controle e custoso em materiais como os aços rápidos temperados e revenidos. Verificou-se que a metodologia utilizada para obtenção e ensaio de corpos de prova chevron foi de fácil execução (comparada à metodologia convencional) permitindo grande número de experimentos. Para verificar a consistência dos resultados, em algumas condições, também se utilizou a metodologia convencional segundo a ASTM E 399-90, cujo pré-trincamento foi feito utilizando os procedimentos propostos por Harris e Dunegan. Os resultados obtidos para os aços fundidos foram correlacionados com os obtidos para outros aços rápidos convencionais (VM2, M2 Thyssen) e um aço rápido sinterizado (SINTER 23). A microestrutura foi caracterizada utilizando-se técnicas de ataques metalográficos diferenciais, metalografia quantitativa manual e computadorizada e microscopia eletrônica de varredura. A avaliação microestrutural indica que não ocorreu precipitação eutética do carboneto M6C, em nenhuma das ligas fundidas. O carboneto M2C apresenta morfologia tanto irregular (plaquetas – tipo 1) quanto regular-complexa (lamelas – tipo 2). As ligas I, III e IV, apresentaram a predominância da morfologia tipo 1 enquanto que a liga II modificada pelo nitrogênio, apresentou apenas a morfologia tipo 2. O carboneto MC apresentou-se com morfologia regular-complexa. Medidas do espaçamento interdendrítico indicam que não houve influência significativa dos elementos modificadores sobre este parâmetro. Ensaios de resistência à flexão, indicam pouca influência dos elementos modificadores, mas forte influência dos tratamentos térmicos sobre o limite de resistência à ruptura transversal do aço fundido. Em todas as ligas, a resistência à flexão cresceu com o tempo de tratamento a 1200°C, bem como com a temperatura de decomposição em tratamentos por 2 horas. Análise das fraturas por microscopia eletrônica de varredura indicou que o crescimento das trincas se deu na região interdendrítica. O aço convencional apresentou resistência à ruptura transversal muito superior à dos aços fundidos. Os ensaios de tenacidade à fratura apresentaram resultados compatíveis com a literatura para os aços AISI M2 convencional e SINTER 23. Os resultados obtidos para o aço fundido, indicam queda nos valores de tenacidade à fratura nos materiais tratados a 1050°C com o avanço do tempo de tratamento; pouca variação dos valores com o tempo nas amostras tratadas a 1150°C; e aumento significativo da tenacidade à fratura com o tempo de tratamento a 1200°C. Os valores de tenacidade obtidos para os aços rápidos fundidos foram mais elevados que os obtidos para os materiais trabalhados e para o material sinterizado. / Fracture Toughness of four cast alloys with chemical composition based on the High-Speed Steel AISI M2 were measured. One of the alloys (alloy I) had the conventional AISI M2 composition, while the other three were modified by the addition of N (alloy II), Ce (alloy III) and Sb (alloy IV). The cast alloys were heat-treated in order to promote the decomposition of the M2C carbide as well as spheroidize and coarsen the product M6C e MC carbides. The method chosen for measuring fracture toughness was based on the use of short rod and bar chevron notched samples, according to ASTM E1304 – 97, in order to evade the need for fatigue pre-cracking, notoriously difficult for High Speed Steels quenched and tempered. The chevron-notch method proved straightforward and allowed for successful testing a great number of specimens. Conventional compact sample fracture toughness, according to ASTM E 399-90, with pre-cracking obtained using Harris-Dunegan drop-weight procedure, was used to validate the results. The results for cast alloys were compared with conventionally produced High Speed Steels (VM2, M2 Thyssen) and with a powder metallurgy High Speed Steel (SINTER 23). Microstructural characterization was performed using selective etching of polished surfaces, manual and automated quantitative metallography and SEM. Microstructural evaluation of as-cast alloys showed that there was no eutectic precipitation of M6C carbides. The M2C carbides show an irregular eutectic morphology (Type 1- plates) as well as a regular-complex eutectic morphology. Measurements of interdendritic spacing did not detect any effect of the modification. The bending test rupture strengths did not vary with the addition of modifying elements, but increased with the time and temperature of decomposition, spheroidization and coarsening of carbides. Rupture strengths increased with the heat-treatment time at 1200°C as well as with increasing temperatures for 2 h heat-treatments. SEM examination of the fracture surfaces showed that crack preferential growth path was interdendritical. Conventional High Speed Steels tested in bending presented better results for the rupture strength than cast steels. Fracture toughness results for M2 conventional steels and for the SINTER 23 steel were similar to the results from the literature. Fracture toughness results obtained for cast steels diminished with increasing decomposition time at 1050°C, did not change much with increasing decomposition time at 1150°C, increased markedly withy increasing decomposition times at 1200°C. The fracture toughness results for the as-cast steels were higher than the results obtained for the wrought steels and for the powder metallurgy steel.

Esta tese investiga o modo de organização dos domínios nominal, verbal e dos adjetivos em Português do Brasil (PB), tendo como guia a aceitabilidade de sentenças com todo. Para o inglês, a natureza do parâmetro orienta a seleção de argumentos por operadores; já para o PB, o que importa é a oposição entre tipos de escala. O PB não tem determinantes que distingam entre nome contável e massivo, como much e many. O operador aspectual progressivo não modifica estados em inglês, mas em PB sim. Em inglês, very seleciona adjetivos de parâmetro relativo. Em PB, muito + adjetivo tem parâmetro relativo, e todo + adjetivo tem parâmetro absoluto. Todo é um operador interdomínios, sensível aos tipos de escala. Todo modifica a relação de predicação. Todo impõe condições (quantitativas) sobre como a saturação de um predicado por certo argumento deve ocorrer. Todo não é nem um modificador nominal, nem um quantificador canônico como cada. Todo não cria, apenas modifica uma relação existente. A distribuição que ocorre em sentenças com todo é uma entre as muitas formas de saturação de um predicado por um argumento: uma relação incremental. Se o argumento for quantizado, o predicado necessariamente também se tornará quantizado. Analisamos uma descrição definida (DD) como um sintagma de medida (SM). O artigo definido torna um predicado nominal em denotação quantizada, mas todo não. Relacionamos ser quantizado a ser argumental, e ser cumulativo a ser predicativo. E associamos sentidos diferentes às posições de todo na sentença. / This thesis takes the distribution of todo as a probe for the structure of nominal, verbal and adjective domains in Brazilian Portuguese (BP). Todo is a Degree Modifier (DM) and is sensitive to scale structure. English DMs (e.g., very) select adjectives by their standards; the BP DMs select adjectives only by their scale structure. However, they produce phrases with standard specialization. Todo + adjective shows absolute standard interpretation. We claim that the domains show the same properties in both languages, but the nature of scale standard matters in a distinct level for each one. We claim that todo is neither a noun modifier nor a true quantifier. Todo is a relation modifier. Todo modifies the way the argument saturates the predicate. A quantized incremental argument will make the predicate quantized as well. Todo is not the true source of distributivity, since incremental relations occur even in its absence. Definite Descriptions are treated as measure phrases. The definite article relates noun predicates to situations. So it will change a bare noun into a quantized denotation, which todo cannot do. Each land site corresponds to a different meaning for floating todo.

Le moteur à combustion, utilisé dans l’automobile est en perpétuelle évolution pour des raisons économiques et écologiques. Pour parvenir à de faibles consommations de carburant et émissions polluantes, l’un des axes étudiés est la réduction des pertes mécaniques par frottement du moteur qui constituent 15 à 20% de la consommation totale d’énergie du moteur. 50% de ces frottements proviennent des contacts Segment-Piston- Chemise et de la liaison Maneton-Bielle-Coussinet. De ce fait la compréhension de la tribologie de ce contact, l’optimisation de la lubrification et le vieillissement des lubrifiants deviennent primordiaux. L’objectif de cette thèse est d’étudier les mécanismes de lubrification de ces contacts segment/chemise et maneton/coussinet, et en particulier de comprendre l’influence du couplage additif, surface et matériau dans les différentes régimes de lubrification. Il s’agira de répondre à la question : comment maîtriser le frottement et l’usure en contrôlant la chimie du lubrifiant, la topographie et le matériau ? La démarche expérimentale choisie s’appuie sur l’analyse du comportement tribologique de deux additifs modificateurs de frottement sans cendres d’une part, puis sur l’impact du matériau et enfin sur l’influence de la topographie d’autre part. L’analyse de la cinétique d’évolution du coefficient de frottement et des traces d’usure en régime limite ont notamment permis d’identifier les mécanismes de réduction de frottement induits par les deux modificateurs étudiés. / The combustion engine used in automotive industry is constantly changing for economic and ecological reasons. To achieve low fuel consumption and pollutants emissions, one of research axes studied is the reduction of the mechanical friction loss of the motor which constitute 15-20 % of the total energy consumption of the engine. 50% of these come from friction contacts cylinder /piston rings and conrod bearing. Thereby understanding of tribology of the contact, optimizing lubrication and lubricants aging become paramount. The objective of this thesis is to study the mechanisms of lubrication of these contact (piston ring/cylinder and conrod bearing), and in particular to understand the influence of the additive coupling surface and material in the different lubrication regimes. This will answer the question : how to control the friction and wear by controlling the chemistry of the lubricant, the topography and the material ? The experimental approach chosen is based on the analysis of the tribological behavior of two friction modifiers additives ashless at first time, and on the impact of material and finally the influence of topography on the second time. XPS Analysis of the evolution of the coefficient of friction and wear track under boundary regime have enabled to identify mechanisms to reduce friction induced by the two modifiers studied.

Selon la théorie du syntagme nominal développée par Wilmet (2003), la notion de caractérisant est une notion fonctionnelle qui désigne tous les « accompagnateurs » du nom (ou déterminants) qui modifient l’extension du nom. Cette notion est indépendante des catégories morpho-syntaxique puisqu’on trouve parmi les caractérisants des adjectifs, des syntagmes prépositionnels, des noms, des adverbes, des propositions relatives voire des phrases entières.<p>Les linguistes du français se sont surtout intéressés à la position absolue de l’adjectif (antéposition ou postposition au nom), mais peu à leur ordre relatif. Il était intéressant d’étendre le point de vue à tous les caractérisants parce que le mélange de caractérisants de différentes natures, en particulier la séquence relative de l’adjectif et du complément du nom, pose d’intéressantes questions linguistiques. La notion fonctionnelle montre également sa valeur dans un cadre comparatiste, car différentes langues ne rendent pas le même concept avec la même catégorie morpho-syntaxique.<p>Notre théorie est que la séquence des caractérisants, tant en antéposition qu’en postposition, est régie par une hiérarchie de critères morpho-syntaxiques et sémantiques, en particulier par leur valeur classificatrice, descriptive ou spécificatrice. On a souvent classé les adjectifs en fonction de leur appartenance à une classe sémantique ontologique (couleur, forme, matière…). En réalité, de très nombreux adjectifs et caractérisants n’entrent pas dans ces catégories et ce type de classification n’est pas le premier critère à l’œuvre dans l’ordre des mots. <p>Le syntagme nominal apparaît dès lors comme structuré en différentes couches concentriques autour du nom ;il est délimité en antéposition par les quantifiants et en postposition par les caractérisants spécificateurs qui lui font en quelque sorte pendant. On observera dès lors d’intéressants phénomènes de sens et d’acceptabilité grammaticale dans le jeu des quantifiants et des caractérisants. Inversement, la position relative d’un caractérisant influe sur sa valeur. On pourrait résumer ces effets de sens par la formule :on dit d’abord ce que c’est, ensuite comment c’est, et enfin lequel c’est. De manière très générale donc, on observe que l’orientation des déterminants se fait selon un axe intrinsèque-extrinsèque ou objectif-subjectif.<p>L’étude d’expressions dans d’autres langues et dans des domaines spécialisés (cuisine, appellations officielles incluant des adjectifs géographiques, localisation de logiciels et chimie organique) permet de valider cette hypothèse tout en montrant que l’ordre des mots est un phénomène de génération, propre à chaque langue car la traduction modifie la nature morpho-syntaxique et peut modifier la valeur des caractérisants. <p>La partie technique de la thèse a exploité des techniques de traduction assistée par ordinateur, de traduction automatique et de traitement du langage, elle a fait appel aux langages de balisage standards de la famille XML pour la représentation des corpus et des règles ainsi que pour la réalisation des procédures. Les corpus spécialisés ont été constitués par alignement de corpus monolingues ou par traduction. Ils ont tous été mis au format XML ;les règles de traduction ont été formalisées dans le même format et elles ont été implémentées en XSLT. La formalisation des corpus en assure la portabilité et facilite les recherches de structures grammaticales sur un corpus catégorisé. Les corpus parallèles sont en outre d’une grande aide pour les traducteurs. Enfin, l’automatisation permet de valider les règles linguistiques proposées. / Doctorat en philosophie et lettres, Orientation langue et littérature / info:eu-repo/semantics/nonPublished

Skeletal muscle wasting is a consequence of numerous physiological conditions, including denervation, corticosteroid treatment, immobilization, and aging. The E3 ubiquitin ligases, MuRF1 and MAFbx, are induced under nearly all atrophy conditions and are believed to play a key role in protein degradation in atrophying muscle. However, the preliminary data described in this study provides new evidence that MuRF1 may also act as a transcriptional modulator of atrophy-induced gene activity, including the regulation of MAFbx and MuRF1 expression. To characterize the transcriptional regulation of MuRF1 and MAFbx, reporter gene constructs containing fragments of the proximal promoter regions of these genes were developed, transfected into C2C12 cells with or without a MuRF1 expression plasmid and monitored for differences in reporter gene activity. The MuRF1 and MAFbx reporters each showed repressed activity in cells ectopically expressing MuRF1 compared to cells that did not overexpress MuRF1. Furthermore, ectopic expression of the myogenic regulatory factors (MRFs), MyoD1 and myogenin, caused significant activation of the MuRF1 and MAFbx reporter constructs. However, co-overexpression of MuRF1 with MyoD1 or myogenin resulted in reversal of MRF induction of reporter gene activity, and synergistic repression of a constructed E-box reporter system. To further characterize the role of the MuRF1 gene product in repression of MuRF1 expression, a MuRF1 RING domain mutant and a MuRF1 c-terminal mutant were created. The mutant constructs were then co-transfected along with MRF expression plasmids and the MuRF1 reporter construct into C2C12 cells and reporter gene activity was assessed. The MuRF1 RING mutant failed to reverse MRF activation of the reporter gene, while the c-terminal mutant successfully reversed activation of the reporter gene. These findings suggest that ubiquitin ligase activity is required for MuRF1 transcriptional regulatory effects. These data offer exciting evidence of a potential new function for MuRF1 as a transcriptional modulator of atrophy-induced changes in gene expression.

Les amines grasses sont présentes dans la formulation de lubrifiants automobiles, en tant que modificateurs de frottement organiques (MFO), afin d'atténuer les effets négatifs entraînés par le frottement et l'usure induits au sein des pièces sujettes aux conditions limites (c'est-à-dire, sous haute pression et basse vitesse de glissement). Outre leurs propriétés de lubrification, ces additifs présentent l'avantage d'être compatibles avec les systèmes de dépollution des gaz d'échappement, puisque leur composition organique est exempte d'éléments nocifs, tels que le soufre, le phosphore et certains métaux. Ainsi, un protocole de calcul en dynamique moléculaire classique a été mis en place et utilisé pour étudier, à l'échelle moléculaire, les propriétés des surfactants. En particulier, trois mécanismes d'action ont été considérés, à savoir : leur diffusion dans un milieu liquide, leur adsorption sur des substrats solides, et leur comportement en frottement. Dans ce contexte, différents facteurs associés à la structure des constituants des lubrifiants ont été analysés, notamment leur effet sur la performance des MFO. Les simulations révèlent que : (i) Diffusion – le coefficient de diffusion des composés aminés sont considérablement impactées par les caractéristiques de l'huile de base (exemple: leur polarité et masse moléculaire), sachant que les modèles de solvant les plus polaires et les plus lourds provoquent le ralentissement du flux diffusif des MFO ; par ailleurs, la structure des additifs jouent également un rôle dans leur diffusion, où les molécules les plus petites et les moins polaires s'avèrent relativement les plus mobiles. (ii) Adsorption – les amines primaires réagissent chimiquement avec une surface d'oxyde de fer, en formant des monocouches auto-assemblées, dont l'organisation et l'épaisseur augmentent avec leur taux de recouvrement. (iii) Frottement – les films adsorbés contenant d'amines constituées d'une chaîne hydrocarbonée C18 linéaire et saturée sont capables de réduire le frottement d'un système modèle représentant un nano-contact en régime limite ; en plus, leur efficacité dépend de la microstructure développée par les amines adsorbées sur les substrats sous compression et cisaillement ; d'ailleurs, les films permettant la formation de(s) plan(s) de glissement bien défini(s) entre les molécules organiques confinées sont davantage disposés à diminuer la résistance de glissement. Par conséquent, ces études ont permis de confirmer l'intérêt de l'apport d'une approche numérique complémentaire aux techniques expérimentales dans le but de comprendre les phénomènes élémentaires des systèmes tribologiques. / Fatty amines and their derivatives are employed as organic friction modifiers (OFM) in lubricant oils in order to mitigate the negative effects of friction and wear, both induced by the moving and rubbing components of an internal combustion engine that are subjected to boundary lubrication conditions (i.e., high contact pressure and low sliding velocity). In addition to their tribological performance, these additives exhibit the benefit of being compatible with exhaust aftertreatment systems that equip the current light-duty vehicles, owing to their sulfur- and phosphorus-free chemical composition. For these reasons, we have developed a computational protocol, composed of equilibrium and non-equilibrium (classical) molecular dynamics simulations, in order to gain a deeper understanding into their mechanisms of action at nanoscale, and in particular into their diffusion, adsorption and friction behaviors. In this context, the influence of different molecular structure factors – related to lubricant constituents – on OFM working performance were investigated. The obtained results have shown that: (i) Diffusion – OFM diffusivity is substantially affected by the base oil structure and chemistry (e.g., polarity and molar mass), where solvents with relatively larger and higher polar groups tend to slow down their diffusive rate; besides, the OFM dynamics in liquid phase is also impacted by their own composition, being the molecules with relatively smaller and less polar structure the most mobile additives. (ii) Adsorption – primary alkyl amines do chemisorb onto iron-oxide substrates, thereby forming molecular films whose packing order and thickness increase with increasing surface coverage. (iii) Friction – adsorbed layers containing primary amines with linear, saturated, C18 hydrocarbon tails are able to reduce friction in a single-asperity, boundary nano-contact model, where their efficiency is dependent on their molecular ordering under confinement and shear; in addition, the organic films allowing the formation of well-defined slippage interface(s) with little molecular interdigitation are more prone to diminish the sliding resistance of solid substrates in relative motion.Therefore, those findings are expected to foster the exploration and development of computational simulation approaches, as a complement of experimental techniques, to investigate the fundamental phenomena present in tribological-relevant engineering systems.

The increasing demand for more readily bio-degradable, renewable and non-toxic environmentally adaptive lubricants with a lower degree of bioaccumulation has escalated the investigation of water-based lubricants as the potential alternatives for conventional mineral-based oils. Water is an excellent environmentally adapted lubricant; however, it is a low viscous fluid and holds downsides of having corrosive nature and extremely low pressure-viscosity coefficient leading to insufficient load-carrying capacity. These shortcomings make pure water a poor choice for operations involving high load and low speed, for instance, within hydropower applications. Therefore, the choice of appropriate modifiers and additives is crucial to improve the viscosity, friction-reducing performance and anti-wear properties of water as a base lubricant. Appropriate selection and combination of bearing materials also significantly improve the tribological performance of the lubricants. In the presented work, tribological behavior of polyvinylpyrrolidone (PVP) and poly(sodium 4-styrenesulfonate) (PSS) thickening agents with water as a base fluid in the lubrication of pure UHMWPE and SCF reinforced UHMWPE bearing materials has been investigated individually under reciprocating tribometer. The results showed that both PVP and PSS are excellent viscosity modifiers. PVP exhibited excellent friction-reducing and anti-wear performance, while PSS revealed increased wear rates with an insignificant reduction of friction coefficients. This study aims to explore the potential for using newly developed water-based lubricants in the replacement of traditional mineral-based lubricants for hydropower turbine bearings.