Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The objective of this study was to evaluate carcass characteristics, the non carcass components, the lipid profile and the sensorial characteristics of meat from steers finished in feedlot fed diets containing different levels of inclusion of soybean soapstock. We used 30 Nellore and Charolais-Nellore crossbred steers with initial mean age of 20 months and initial mean weight of 20 months and 328.3 kg (±18.8 kg) were allotted to five dietary treatments: 0, 30, 60, 90 and 120 g of soybean soapstock/kg dry matter (DM) of diet . The diet consisted of forage(corn silage):concentrate ratio of 39:61 (DM basis), and was offered "ad libitum" during 84 days. A inclusão de até 120 g de borra de soja/kg de MS na dieta não alterou o peso de abate e os rendimentos de carcaça quente e fria, assim como os componentes teciduais músculo, gordura e osso. The inclusion up to 120 g of soybean soapstock/kg DM in the diet did not alter the slaughter weight and hot and cold carcass yields, as well as the muscle, fat and bone tissues. It also did not alter the empty body weight and yield, and hot and cold carcass yields adjusted for the empty body weight. The relative weight of the blood decreased with the addition of up to 55 g of soybean soapstock/kg DM in the diet, but the inclusion of up to 120g/kg DM in the diet promoted a linear increase in the relative weight of the lung and spleen, a linear reduction of the relative weight of the omasum and rumen fat. The kidney fat deposition, when adjusted for empty body weight, increased with the inclusion of up to 50 g of soybean soapstock/kg DM. The total weight of external components, vital, gastrointestinal and internal fat did not differ. With respect to meat quality, including between 83 to 91 g soybean soapstock/kg of diet DM promoted the highest levels of Vacenic (C18: 1 trans -11) and CLA (C18: 2 cis-9 trans-11) fatty acids, however, promoted also the highest levels of trans fats in the steers meat. The levels of fatty acids of the omega-3 group decreased linearly with the inclusion of dietary soybean soapstock , increasing the omega-6:omega-3 ratio in the steers meat. The lipid content increased linearly with the addition of soybean soapstock , but the content of cholesterol remained similar. The inclusion of dietary soybean soapstock did not affect meat marbling, color, palatability, juiciness, tenderness, and losses of the thawing and cooking liquid. / Objetivou-se nesse estudo avaliar as características da carcaça, dos componentes não integrantes da carcaça e do perfil lipídico e sensorial da carne de novilhos terminados em confinamento, alimentados com dietas contendo diferentes níveis de inclusão de borra de soja. Foram usados 30 novilhos Nelore e cruzas Charolês-Nelore com idade média inicial de 20 meses e peso médio inicial de 328,3 kg (±18,8 kg), distribuídos em cinco tratamentos alimentares: 0; 30; 60; 90 e 120 g de borra de soja/kg de matéria seca (MS) da dieta. A dieta foi constituída de volumoso (silagem de milho):concentrado com relação de 39:61 (com base na MS), e ofertada à vontade durante 84 dias. A inclusão de até 120 g de borra de soja/kg de MS na dieta não alterou o peso de abate e os rendimentos de carcaça quente e fria, assim como os componentes teciduais músculo, gordura e osso. A inclusão de até 120 g de borra de soja/kg de MS na dieta também não alterou o peso e rendimento de corpo vazio, e rendimentos de carcaça quente e fria, ajustada ao peso do corpo vazio. O peso relativo do sangue reduziu com a inclusão de até 55 g de borra de soja/kg de MS na dieta, porém a inclusão de até 120g/kg de MS na dieta promoveu aumento linear no peso relativo do pulmão e baço, redução linear no peso relativo do omaso e da gordura ruminal. A deposição de gordura renal, quando ajustada ao peso de corpo vazio, aumentou com a inclusão de até 50 g de borra de soja/ kg de MS. Os pesos totais dos componentes externos, vitais, gastrintestinais e das gorduras internas não diferiram. Com relação a qualidade da carne, a inclusão entre 83 a 91 g de borra de soja/kg de MS da dieta promoveu os maiores teores dos ácidos graxos Vacênico (C18:1 trans-11) e CLA (C18:2 cis-9 trans-11), entretanto, promoveu também os maiores teores de gorduras trans na carne dos novilhos. Os teores de ácidos graxos da família ômega-3 reduziu linearmente com a inclusão da borra de soja na dieta, refletindo com isso, no acréscimo da relação ômega-6:ômega-3 na carne de novilhos. O teor de lipídios aumentou linearmente com a inclusão da borra de soja, porém o de teor de colesterol se manteve semelhante. A inclusão da borra de soja na dieta não alterou a marmorização, cor, palatabilidade, suculência, maciez, e perdas de líquidos ao descongelamento e cocção da carne.

Il existe deux populations d’adipocytes thermogéniques, les adipocytes bruns du tissu adipeux bruns et les adipocytes ‘’brites’’ qui apparaissent au sein du tissu adipeux blanc. Récemment, la caractérisation d’adipocytes bruns et brites fonctionnels chez l’homme adulte a permis d’envisager de nouvelles approches nutritionnelles et thérapeutiques pour traiter l’obésité. Mon projet de thèse a porté sur l’étude des effets des acides gras polyinsaturés ω6 et ω3 d’origine alimentaire sur la conversion des adipocytes blancs en brites, d’abord chez l’homme in vitro puis chez les rongeurs in vivo. Nous avons pu ainsi démontrer que l'acide arachidonique ω6 à l’origine de nombreux métabolites oxygénés, exerce 1) un effet inhibiteur sur la formation des adipocytes brites grâce aux prostaglandines E2 et F2α, et 2) un effet inducteur via la prostacycline. En effet, celle-ci active la conversion des adipocytes blancs en brites par une voie impliquant le récepteur membranaire IP et les récepteurs nucléaires PPARs. En nous basant sur les recommandations nutritionnelles actuelles chez l’Homme, qui ont pris en considération l’insuffisance de l’apport en acides garsω3 par rapport à l’excès des ω6, nous avons pu montrer chez la souris qu’une supplémentation en acides gras ω3 dans le régime alimentaire était capable d’inhiber l’effet néfaste des acides gras ω6 et d’activer le tissu adipeux brun. Nos résultats démontrent l’importance de la biodisponibilité de l’acide arachidonique dans la biologie du tissu adipeux et permettent de renforcer l’idée que le rééquilibrage du ratio ω6/ω3 est un outil de choix dans la prévention du surpoids et de l’obésité et les maladies métaboliques associées / There are two types of thermogenic adipocytes able to use fatty acids and glucose to produce heat. We distinguish brown adipocytes from the brown adipose tissue and ‘’brite’’ adipocytes which occur into the white adipose tissue. Recently, the characterization of functional brown and brite adipocytes in adult humans has led to the consideration of their use to treat obesity by increasing energy expenditure. My thesis project was to study the effect of dietary polyunsaturated fatty acids, on the conversion of white into brite adipocytes, in vitro and in vivo, in humans and rodents respectively. We demonstrated that arachidonic acid ω6, precursor of prostaglandins, has 1) an inhibitory effect on the recruitment of brite adipocytes via prostaglandins E2 and F2α and 2) an activatory effect via prostacyclin. In fact, prostacyclin induces the conversion of white into brite adipocytes through the IP receptor and the PPARs signaling pathways. Based on human present nutritional recommendations, we demonstrated that a supplementation of ω3 fatty acids in mice diet was able to inhibit the negative effect of ω6 fatty acids and activate brown adipose tissue. Our data highlights the importance of arachidonic acid bioavailability on the biology of adipose tissue and reinforce the idea that an equilibrate ω6/ω3 ratio is a tool that can be used to prevent overweight obesity and associated metabolic disorders

Submitted by Jessica Franzão Ganzaroli (jessicaganzaroli@hotmail.com) on 2018-06-14T19:04:24Z No. of bitstreams: 1 Jéssica Franzão Ganzaroli de Oliveira.pdf: 1826504 bytes, checksum: 014ea667caf3e8adf1c194b73c589410 (MD5) / Approved for entry into archive by Fabio Sampaio Rosas null (fabio@dracena.unesp.br) on 2018-06-15T13:16:14Z (GMT) No. of bitstreams: 1 oliveira_jfg_me_dra.pdf: 1826504 bytes, checksum: 014ea667caf3e8adf1c194b73c589410 (MD5) / Made available in DSpace on 2018-06-15T13:16:14Z (GMT). No. of bitstreams: 1 oliveira_jfg_me_dra.pdf: 1826504 bytes, checksum: 014ea667caf3e8adf1c194b73c589410 (MD5) Previous issue date: 2018-04-26 / A relação entre o consumo de ácidos graxos ω-6/ω-3 na dieta é um importante fator para determinar a ingestão adequada de ácidos graxos bem como prevenir o aparecimento de doenças, podendo interferir no desempenho, na qualidade de ovos e no comportamento plasmático dos lipídios das galinhas poedeiras. Estes ovos podem trazer benefícios para os consumidores que estão cada vez mais preocupados com a ingestão de alimentos saudáveis. O objetivo desta pesquisa foi avaliar diferentes relações ômega-6/ômega-3, visando obter incremento no desempenho, nas variáveis bioquímicas séricas e na qualidade dos ovos de galinhas poedeiras às 81 semanas de idade. Para tanto, foram utilizadas 224 poedeiras da linhagem Hysex White com 81 semanas de idade, distribuídas em um delineamento experimental inteiramente casualizado constituído de sete tratamentos com oito repetições de quatro aves por gaiola, perfazendo um total de 56 gaiolas. Os tratamentos experimentais consistiram em sete diferentes relações de ácidos graxos ω-6/ω-3: 1,0:1,0; 2,0:1,0; 4,0:1,0; 8,0:1,0; 16,0:1,0; 32,0:1,0; 64,0:1,0. Para a formulação dessas dietas foram utilizados o óleo de girassol, rico em ômega-6 e o óleo de linhaça, rico em ômega-3. Não foram observadas diferenças significativas para as variáveis de desempenho, exceto para consumo de ração que aumentou linearmente conforme ascendeu a relação ω-6/ω-3 da dieta, destacando que a inclusão de óleo de linhaça em maiores proporções na dieta resultou em menor consumo de ração, indicando que o óleo de linhaça por ser rico em ômega-3 proporciona sensação de saciedade no animal. Os valores encontrados para as variáveis de qualidade de ovos também não apresentaram diferença significativa entre as dietas, sendo possível a suplementação da ração com ácidos graxos polinsaturados, em diferentes relações, sem promover alterações na qualidade de ovos com exceção da unidade Haugh, em que observou-se efeito quadrático, indicando melhor valor para a relação ω-6/ω-3 de 32. Concluiu-se que o aumento na relação ω-6/ω-3 eleva o consumo de ração das galinhas poedeiras. A relação ω-6/ω-3 de 34,64 proporciona maior unidade Haugh de ovos, diminuindo a partir desse ponto. As demais variáveis de desempenho e de qualidade de ovos permanecem inalteradas. As relações ω-6/ω-3 não influenciam as variáveis bioquímicas séricas das galinhas. / The relation between consumption of ω-6/ω-3 fatty acids in the diet is an important factor in determining the adequate intake of fatty acids and preventing the onset of diseases, which may interfere with performance, egg quality and plasma lipids behavior of laying hens. These eggs can bring benefits to consumers who are increasingly concerned about eating healthy foods. The aim of this study was to evaluate different omega-6/omega-3 ratios, and its influence to increase performance, serum biochemical variables and egg quality of laying hens at 81 weeks of age. For this, 224 laying hens of the Hysex White, 81 weeks old, distributed in a completely randomized experimental design consisting of seven treatments with eight replicates of four poultries per cage, making a total of 56 cages. The experimental treatments consisted of seven different fatty acid ratios ω-6/ω-3: 1.0: 1.0; 2.0: 1.0; 4.0: 1.0; 8.0: 1.0; 16.0: 1.0; 32.0: 1.0; 64.0: 1.0. For formulation of these diets we used sunflower oil, rich in omega-6 and linseed oil, rich in omega-3. No significant differences were observed between variables, except about feed intake that increased linearly as ω-6/ω-3 ratio of the diet rose. This result showed that the inclusion of flaxseed oil in higher proportions can lead to lower intake of ration, indicating that flaxseed oil being rich in omega-3 provides animal satiation. Values found for egg quality variables also did not present a significant difference between diets, indicating the possibility to supplement the diet with polyunsaturated fatty acids, in different ratios, without promoting changes in egg quality, except for Haugh unit, in which it observed quadratic effect. By increasing ω-6/ω-3 ratio also increases feed consumption of laying hens, suggesting better value for the ω-6/ω-3 ratio as 32. The ω-6/ω-3 ratio of 34.64 provides higher Haugh unit of eggs, decreasing from that point. Other performance and egg quality variables remain unchanged. The ω-6/ω-3 ratios did not influence the serum biochemical variables of laying hens.

Orientador: Fernando Antonio Cabral / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos / Made available in DSpace on 2018-08-08T22:12:06Z (GMT). No. of bitstreams: 1 FollegattiRomero_LuisAlberto_M.pdf: 666792 bytes, checksum: 9ae97012c5bd9df738d34f847f6ef5b7 (MD5) Previous issue date: 2007 / Resumo: A extração supercrítica do óleo das sementes de sacha inchi (plukenetia volubilis L.) usando CO2 como solvente é apresentada neste estudo. O objetivo foi investigar os principais efeitos das variáveis de processo como a pressão, a temperatura e o diâmetro médio de partícula (0,387, 0,595 e 0,842 mm) no rendimento da extração. O rendimento de extração aumentou com a diminuição do diâmetro de partícula, indicando a importância do efeito da difusão intra-partícula nas partículas maiores (0,842 mm). A extração supercrítica foi realizada a 30 e 40 MPa, temperaturas de 40, 50 e 60°C, utilizando 0,842 mm de diâmetro de partícula a uma vazão de 1,5L de CO2/min. O rendimento máximo de extração para as sementes trituradas foi de 92%, obtido a 40MPa, 60°C e 0,842 mm de diâmetro médio de partícula. Para extração por prensagem a frio, seguida da extração supercrítica a 40Mpa, 60ºC e 0,716 mm de diâmetro médio geométrico da partícula o rendimento total de extração foi de 99%. A solubilidade do óleo da semente de Sacha inchi em dióxido de carbono supercrítico (SC-CO2) foi medida nas temperaturas de 40 e 60 °C e pressões entre 10 e 40 MPa. Os valores de solubilidade mostraram um comportamento retrógrado, abaixo de 35 MPa a solubilidade diminuiu com o aumento da temperatura.A tendência observada acima desta pressão foi um aumento da solubilidade com o aumento da temperatura a pressão constante. O modelo matemático de Chrastil foi usado para correlacionar os valores experimentais de solubilidade. O conteúdo de óleo determinado com hexano em equipamentos soxhlet foi de 54,32% e o rendimento de óleo extraído por prensagem a frio foi de 46,8%. As características físicas e químicas do óleo foram obtidas. As composições em ácidos graxos do óleo obtido por SC-CO2 e do óleo obtido com hexano não apresentaram diferenças significativas. O principal ácido graxo foi o ácido alfa-linolênico (Ômega-3) aproximadamente 50,5%, seguido peloácido linoléico (34,12%) e ácido aléico (14%). O conteúdo de ácidos graxos livres (AGL) e de tocoferóis (tocoferol e tocotrienol) dos óleos obtidos por SC-CO2, solvente e prensagem a frio foram determinados. O conteúdo de tocoferóis so óleo extraído com SC-CO2 variou de 222,8 a 306,8 mg/100g, do óleo extraído por prensagem a frio foi 278,4 mg/100g e do óleo extraído com hexano foi 238,7 mg/100g. O teor de AGL no óleo extraído com hexano foi de 2,98% (medido como % de ác. Linolênico), ligeiramente menor do que aquele extraído por prensagem a frio (3,75%) e SC-CO2 (3,97-4,26%). O óleo de sementes de Sacha inchi pode ter grande potencial debtro do mercado crescente de óleos especiais / Abstract: The supercritical fluid extraction of oil from sacha inchi (plukenetia volubilis L.) seeds, using Co2 as a solvent, it is presented in this study. The objective was to investigate the main process parameters such as extraction pressure and temperature, mean particle size of (0,387, 0,595 and 0,842 mm) on the extraction yield. The extraction yield increased as the particle size decreased, indicating the importance of the effect of the intraparticle diffusion in larger particles (0,84 mm). The extraction was carried out at operating pressures of 30 and 40 MPa, operating temperatures of 40, 50 and 60°C, particle 0,84 mm and flow rate of CO2 1,5L/min. Maximum extraction yield was 92% obtained at 40 MPa, 60°C, 0.84 mm of particle sizes and 1.5 L of CO2/min. For the cold-pressed extraction, followed of supercritical extraction 40 MPa, 60ºC and 0,716 mm of geometric average diameter of the particle, the maximum extraction yield was 99%. The solubility of Sacha inchi seed oil in supercritical carbon dioxide (SC-CO2) were measured in the temperatures from 40 to 60 °C and pressures between 10 and 40 MPa. Under working conditions, the values of solubility showed retrograde behavior. Solubility, increase with pressure and temperature above the crossover pressure, which found between 30 and 40 MPa, and decreased with temperature below the crossover pressure. Mathematical modeling (Chrastil) of the solubility. The oil content was 54,32% and 46.80% determined bu solvent extraction and cold-pressed, respectively. Physical and chemical characteristics of the oil were obtained. The results in terms of fatty acid compositions of oil obtained with SC-CO2 were compared with those obtained when hexano was used as the solvent, and no significant differences between the oils extracted by both methods were found. The main fatty acid was alpha-linolênico acid (Ômega-3) making up 50.5%, followed by linoleic acid (34,12%) and oleic acid (14%). The level of FFA and tocol composition (tocoferol and tocotrienol) contents of the oils obtained by SC-CO2, solvent and cold-pressed extraction was determined. Tocol content of the SC-CO2 - extracted oil varied from 222.85 to 306.82 mg/100g, which was higher than that of hexane-extraced oil (238.72 mg/100g) and cold-pressed oil (278.4 mg/100g). The level of FFA in the solvent-extraced oils (2.98%) (% as ác. Linolenic) was lower than cold-pressed extraced oil (3.75%) and SC-CO2)-extraced oils (3.97-4.26%). Sacha inchi seed oil may have potential in the growing specialty oil market / Mestrado / Mestre em Engenharia de Alimentos

About 20 to 25 % of psychiatric patients treated with typical antipsychotics may develop an important movement disorder named tardive dyskinesia, with complex etiology and no effective treatment. Cognitive loss is also associated with antipsychotic treatment being harmful and often difficult to identify. Some studies have shown beneficial effects of Omega 3 polyunsaturated fatty acids on tardive dyskinesia and on cognition. Considering the available evidences, we conducted a randomized, double-blind, placebo-controlled, clinical trial, which evaluated the effect of fish oil supplementation rich in n-3 polyunsaturated fatty acids (3 g/dia) or placebo (3 capsules / day), for 12 weeks, on motor and cognitive disturbances of patients on use of neuroleptics. Two evaluations were performed, one before supplementation (baseline) and another at the end of it. For this, were used the following evaluation tools: Abnormal Involuntary Movement Scale for tardive dyskinesia and Mini-Mental State Examination for cognition. Peripheral blood samples were collected before supplementation (baseline) and 4, 8 and 12 weeks after, in order to monitor the supplementation effects on biochemical parameters- triglycerides (TG), fasting glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and on parameters of blood clotting- prothrombin time and partial thromboplastin time. The biological material collected was also used to run the Comet Assay in leukocytes with the aim of investigate the treatment effect on the DNA damage index. After 3 months of supplementation, we observed that fish oil caused an improvement of 18.5 % in tardive dyskinesia, while cognitive performance did not change when compared with the baseline assessment. Furthermore, lipid profile of the patients was not modified, fasting glucose was reduced in all assessments and prothrombin time increased in the last evaluation. In addition, fish oil did not show genotoxic effect (DNA damage index did not change). Therefore, we have demonstrated the therapeutic potential of fish oil rich in Omega 3 on tardive dyskinesia of patients treated with neuroleptics and its low risk of side effects. The increase of prothrombin time suggests a possible anticoagulant effect, requiring its monitoring during chronic treatment. / Cerca de 20 a 25 % dos pacientes psiquiátricos tratados com antipsicóticos típicos podem desenvolver uma importante síndrome motora denominada discinesia tardia (DT), de etiologia complexa e ainda sem tratamento efetivo. Perdas cognitivas também estão associadas ao uso desses medicamentos, sendo muitas vezes de difícil identificação e igualmente prejudiciais. Alguns estudos têm demonstrado efeitos benéficos dos ácidos graxos poliinsaturados Omega 3 (AGPI n-3) sobre a DT e sobre a cognição. Considerando as evidências disponíveis, realizamos este trabalho que consistiu de um ensaio clínico randomizado, duplo-cego, controlado por placebo. Avaliamos os efeitos da suplementação com de óleo de peixe rico em AGPI n-3 (3 g/dia) ou placebo (3 cápsulas/dia) sobre distúrbios motores e cognitivos de pacientes sob uso de neurolépticos, por um período de 12 semanas. Foram efetuadas duas avaliações, uma antes da suplementação (basal) e outra ao final da mesma. Para isso utilizamos as seguintes ferramentas de avaliação: Escala de Movimentos Involuntários Anormais (EMIA), para a DT e Mini-Exame do Estado Mental (MEEM), para a cognição. Amostras de sangue periférico foram colhidas antes da suplementação (basal) e 4, 8 e 12 semanas após, com o propósito de acompanhar seus os efeitos sobre parâmetros bioquímicos- triglicerídeos (TG), glicemia de jejum, colesterol total, colesterol ligado à lipoproteína de alta densidade (HDL-C) e colesterol ligado à lipoproteína de baixa densidade (LDL-C), bem como sobre parâmetros de coagulação sanguínea- tempo de protrombina (TP) e tempo de tromboplastina parcial (TTP). Com o material biológico colhido, também executamos o Ensaio Cometa em leucócitos, para investigar a influência do tratamento sobre o índice de dano no DNA. Após 3 meses de suplementação, observamos que o óleo de peixe produziu uma melhora de 18,5 % na DT, enquanto o desempenho cognitivo não sofreu alteração em relação à avaliação basal. Por sua vez, o perfil lipídico dos pacientes não foi modificado, a glicemia de jejum foi reduzida em todas as avaliações e o TP aumentou na última avaliação. Ainda, o índice de dano no DNA não foi alterado, mostrando que o óleo de peixe não apresentou efeito genotóxico. Com isso, demonstramos o potencial terapêutico do óleo de peixe rico em Omega 3 sobre a DT de pacientes tratados com neurolépticos e seu baixo risco de efeitos colaterais. O aumento do TP sugere um possível efeito anticoagulante, necessitando de acompanhamento durante tratamentos crônicos.

Le but du présent travail est d’évaluer le potentiel d’oméga-3 à induire la fonction endothélial, et à inhiber la contraction des artères coronaires en réponse aux plaquettes activées.L’induction des relaxations dépendantes de l’endothélium est affecté à la fois par le ratio et la pureté des formulations, avec un effet maximal obtenu pour la formulation EPA:DHA 6:1 à haut degré de pureté via une activation redox-sensible des voies de signalisation PI3-kinase/Akt et/ou MAPKs menant à l’activation de eNOS. La formulation EPA:DHA 6:1 inhibe les contractions induites par les plaquettes impliquant la sérotonine dans les artères coronaires de porc, et les contractions à la sérotonine dans les artères coronaires porcines et mammaires internes humaines, principalement par une augmentation de la formation endothéliale de NO. Ces résultats indiquent que la formulation optimisée EPA:DHA 6:1 exerce un effet bénéfique sur le système cardiovasculaire via l’activation de la fonction endothéliale. / The aim of the present work was to evaluate both the potency of omega-3 formulations to induce the endothelial function and the effect of omega-3 on the platelet-induced coronary artery contraction.The endothelium-dependent relaxations induced by EPA:DHA formulations is dependent on both the ratio and the purity of the formulation, with the maximal effect obtained with a highly purified EPA:DHA 6:1 ratio through a redox-sensitive activation of PI3-kinase/Akt and/or MAPKs pathways and subsequent activation of eNOS. The EPA:DHA 6:1 formulation inhibits the platelet-induced serotonin-mediated contraction of porcine coronary rings and the 5HT-induced contraction in both porcine coronary artery and human internal mammary artery rings, mainly due to an increased endothelial formation of NO. Taken together, the present findings indicate that the optimized EPA:DHA 6:1 formulation is able to exert potent beneficial cardiovascular effects through the activation of the endothelial function.

The cancers of the skin, melanoma and the keratinocyte cancers, basal cell andsquamous cell carcinomas (BCC and SCC), are among the most common cancersin white populations. While ultraviolet radiation (UVR) is their principal cause,links with non-UVR-related factors have also been noted. Ultimately, theinteraction of these elements results in malignancy however, understanding oftheir specific contributions remains incomplete. This thesis reports findings fromsix studies aiming to investigate gaps in current knowledge of the role of UVR andnon-UVR-related risk factors on skin cancer. The papers are groupedaccording to the aspects of skin cancer epidemiology and aetiology they address. The first two papers address the descriptive epidemiology of melanoma inEngland, a country with low ambient solar UVR. They arise from ecologicalstudies using national melanoma registration data and document rising trends inmelanoma incidence by anatomic site (Paper 1), and by region of residence andsocio-economic deprivation (Paper 2). Their findings were consistent with thesuggestion that increases in recreational UVR exposure are driving rises inmelanoma rates. These results emphasise both the need to closely monitor UVRexposure and melanoma trends and the importance of public health campaigns. The second group of three papers considers the assessment of associations ofnutritional factors with keratinocyte cancer. Two studies use data from aprospective cohort to evaluate the relationship between dietary intake (Paper 3)and blood concentrations (Paper 4) of omega-3 and omega-6 polyunsaturatedfatty acids (PUFA) in relation to BCC and SCC risk. Associations with both PUFAtypes were observed. In addition, Paper 5, a three-way correlational assessment,demonstrated that questionnaire and blood circulating levels of omega-3 PUFAwere highly correlated with measures of skin bioavailability. Collectively, thesestudies give evidence for associations of these nutrients with skin cancer and forthe utility of both intake and biomarker measures for assessing the relationships. The final paper explores the relationship between a widely cited non-UVR riskfactor, namely scars and cancers of the skin. It reports a systematic review of allpublished observational studies quantifying this association. While innumerablecase reports were found, quantitative analyses were rare. The review identifieda major gap in the literature where knowledge of scar malignancies is notevidence-based, but rather founded mainly on cumulative anecdotal reporting. Taken together, this body of published work highlights the largely unrecognisedcomplexity of the aetiology of cancers of the skin. Future research must bebroad in scope in order to advance understanding of the interaction betweenUVR and other risk factors and to provide a base for health messages aimed atreducing the burden of these malignancies.

Cette thèse traite de la theorie de la preuve pour les logiques a points fixes, telles que le μ-calcul, lalogique lineaire a points fixes, etc. ces logiques sont souvent munies de systèmes de preuves finitairesavec des règles d’induction à la Park. Il existe néanmoins d’autres sytèmes de preuves pour leslogiques à points fixes, qui reposent sur la notion de preuve infinitaire, mais qui sont beaucoupmoins developpés dans la litterature. L’objectif de cette thèse est de pallier à cette lacune dansl’état de l’art, en developpant la théorie de la preuve infnitaire pour les logiques a points fixes,avec deux domaines d’application en vue: les langages de programmation avec types de données(co)inductifs et la vérification des systèmes réactifs.Cette thèse contient trois partie. Dans la première, on rappelle les deux principales approchespour obtenir des systèmes de preuves pour les logiques à points fixes: les systèmes finitaires avecrègle explicite d’induction et les systèmes finitaires, puis on montre comment les deux approchesse relient. Dans la deuxième partie, on argumente que les preuves infinitaires ont effectivement unréel statut preuve-theorique, en montrant que la logique lineaire additive multiplicative avec pointsfixes admet les propriétés d’élimination des coupures et de focalisation. Dans la troisième partie,on utilise nos developpements sur les preuves infinitaires pour monter de manière constructive lacomplétude du μ-calcul lineaire relativement à l’axiomatisation de Kozen. / The subject of this thesis is the proof theory of logics with fixed points, such as the μ-calculus,linear-logic with fixed points, etc. These logics are usually equipped with finitary deductive systemsthat rely on Park’s rules for induction. other proof systems for these logics exist, which relyon infinitary proofs, but they are much less developped. This thesis contributes to reduce thisdeficiency by developing the infinitary proof-theory of logics with fixed points, with two domainsof application in mind: programming languages with (co)inductive data types and verification ofreactive systems.This thesis contains three parts. In the first part, we recall the two main approaches to theproof theory for logics with fixed points: the finitary and the infinitary one, then we show theirrelationships. In the second part, we argue that infinitary proofs have a true proof-theoreticalstatus by showing that the multiplicative additive linear-logic with fixed points admits focalizationand cut-elimination. In the third part, we apply our proof-theoretical investigations to obtain aconstructive proof of completeness for the linear-time μ-calculus w.r.t. Kozen’s axiomatization.

In the present work, phase transformations in TIMETAL LCB tita- nium alloy and their influence on mechanical properties were studied. Different initial conditions were prepared by solution treating above β-transus immedi- ately followed by heat treatment in α/β temperature regime. These resulted in different grain boundary α thicknesses and contiguities at a fixed α vol- ume fraction. The subsequent ageing response of this material was studied by low temperature ageing at 400 ◦ C, 450 ◦ C and 500 ◦ C. Phase transformations were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and resistivity measurements. Mechan- ical properties were investigated using microhardness measurements and tensile tests. It has been proved that metastable ω phase is formed during annealing at 400 ◦ C and 450 ◦ C. ω particles further transform to very fine precipitates of α phase when exposed to annealing for longer time periods. These fine precip- itates significantly contribute to increase of microhardness and achieving high value of yield stress. Keywords: Metastable beta Ti alloys, phase transformations, microstructure changes, ω phase 1

Förlust av muskelmassa med åldrande försämrar den fysiska funktionen, vilket även minskarlivskvaliteten och kan leda till svaghet och för tidig död. Omega-3-fettsyror stimulerar protein-anabolism och kan därför vara användbart för att förebygga och behandla sarkopeni. Syfte:Syftet med denna studie var att utvärdera effekten av omega-3-fettsyra-tillskott på graden avmuskelproteinsyntes hos vuxna. Metod: Studien är utförd som en litteraturstudie där relevantavetenskapliga och publicerade studier utvärderats och dess resultat har analyserats för attbesvara studiens syfte. Studiernas relevans bedömdes utifrån artiklarnas titel och abstrakt. 234studier i Onesearch, 5 studier i PubMed gicks igenom till en början. 30 abstrakt lästes, 21studier lästes i fulltext, 7 studier baserat på in- och exklusionskriterierna valdes ut till studienefter läst fulltext. Resultat: De flesta studier har utvärderat effekten av omega-3-tillskott hosyngre vuxna 18-30 år och äldre vuxna 65 år och äldre. Även om det finns en relativ brist påstudier som utvärderar effekten av omega-3-tillskott på muskelproteinsyntes (MPS) hos vuxna30-70 år, verkar det som om omega-3 kan främja anabola ökningar vid styrketräning hos äldreindivider. Slutsats: Ytterligare forskning behövs inom detta område för att dra relevantaslutsatser. Denna litteraturstudie drar slutsatsen att omega-3-fettsyror stimulerar syntesen avmuskelprotein hos vuxna och kan vara användbart för att förebygga och behandla sarkopeni. / Loss of muscle mass with aging impairs physical functions, but also reduces quality of life andcan lead to weakness and premature death. Omega-3 fatty acids stimulate protein anabolism andmay therefore be usefull to treat sarcopenia. Purpose: The aim of this study was to evaluate theeffect of omega-3 fatty acid supplements on the degree of muscle protein synthesis in adults.Metod: The study is conducted as a literature study where relevant scientific and publishedstudies, evaluations and its results have been analyzed to answer the purpose of the study. Therelevance of the studies were assessed on the basis of the title and abstract of the articles. 234studies in Onesearch, 5 studies in PubMed were initially reviewed. 30 abstracts were read, 21studies were read in full text, based on the inclusion and exclusion criteria 7 studies wereselected for the study after reading in full text. Results: Most studies have evaluated the effect ofomega-3 supplements in younger adults (18-30 years) and older adults (65 years and older).Although there is a relative lack of studies evaluating the development of omega-3 supplementson MPS in adults 30-70 years, it seems that omega-3 can promote anabolic increases in olderindividuals. Couclusion: Further research is needed in this area to draw relevant conclusions.This literature review concludes that omega-3 fatty acids stimulate the synthesis of muscleprotein in adults and may be useful to prevent and treat sarcopenia.