Yes / Brittleness in manganese steels can be associated with processing in a "wet¿ [micro]climate resulting in the formation of continuous oxide networks. The formation of these networks can be prevented by sintering in an atmosphere, also ¿local¿ in a semiclosed container, adhering to the Ellingham-Richardson oxide reduction criteria. When this requirement is satisfied, however, further types of ductile ¿ brittle transitions are observed. Rapid cooling, typically above 40°C/min, produces enough martensite to render Fe-(3-4)Mn-(0·6-0·7)C material macroscopically brittle. Quenched and conventionally tempered structures remain brittle. It is tentatively suggested that segregation of minor alloying/tramp element(s), as in cast materials, is responsible for this temper embrittlement. To overcome it, heat treatment at a temperature no higher than 200°C, recovery/stress relief, is recommended.

No description available.

No description available.

A proteína nucleolar Nop8p de levedura foi identificada inicialmente através de sua interação com Nip7p e está envolvida na formação da subunidade ribossomal 60S. A depleção de Nop8p em células de levedura leva à degradação prematura dos rRNAs, porém o mecanismo bioquímico responsável por este fenótipo ainda não é conhecido. Neste trabalho, mostramos que a interação de Nop8p com o rRNA 5.8S se dá através de sua região amino-terminal, enquanto que a porção carboxi-terminal é responsável pela interação com Nip7p e complementa parcialmente o defeito no crescimento observado na cepa mutante condicional Δnop8/GAL::NOP8. Além disso, Nop8p media a associação de Nip7p com as partículas pré-ribossomais. Nop8p também interage com a subunidade Rrp6p do exossomo e inibe a atividade do complexo in vitro, sugerindo que a diminuição dos níveis da subunidade ribosomal 60S detectada após a depleção de Nop8p pode ser resultado da degradação dos pré-rRNAs pelo exossomo. Estes resultados indicam que Nop8p pode regular a atividade do exossomo durante o processamento do pré-rRNA. / The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxylterminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Δnop8/GAL::NOP8. Interestingly, Nop8p mediates the association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control exosome function during pre-rRNA processing.

A proteína nucleolar Nop8p de levedura foi identificada inicialmente através de sua interação com Nip7p e está envolvida na formação da subunidade ribossomal 60S. A depleção de Nop8p em células de levedura leva à degradação prematura dos rRNAs, porém o mecanismo bioquímico responsável por este fenótipo ainda não é conhecido. Neste trabalho, mostramos que a interação de Nop8p com o rRNA 5.8S se dá através de sua região amino-terminal, enquanto que a porção carboxi-terminal é responsável pela interação com Nip7p e complementa parcialmente o defeito no crescimento observado na cepa mutante condicional Δnop8/GAL::NOP8. Além disso, Nop8p media a associação de Nip7p com as partículas pré-ribossomais. Nop8p também interage com a subunidade Rrp6p do exossomo e inibe a atividade do complexo in vitro, sugerindo que a diminuição dos níveis da subunidade ribosomal 60S detectada após a depleção de Nop8p pode ser resultado da degradação dos pré-rRNAs pelo exossomo. Estes resultados indicam que Nop8p pode regular a atividade do exossomo durante o processamento do pré-rRNA. / The yeast nucleolar protein Nop8p has previously been shown to interact with Nip7p and to be required for 60S ribosomal subunit formation. Although depletion of Nop8p in yeast cells leads to premature degradation of rRNAs, the biochemical mechanism responsible for this phenotype is still not known. In this work, we show that the Nop8p amino-terminal region mediates interaction with the 5.8S rRNA, while its carboxylterminal portion interacts with Nip7p and can partially complement the growth defect of the conditional mutant strain Δnop8/GAL::NOP8. Interestingly, Nop8p mediates the association of Nip7p to pre-ribosomal particles. Nop8p also interacts with the exosome subunit Rrp6p and inhibits the complex activity in vitro, suggesting that the decrease in 60S ribosomal subunit levels detected upon depletion of Nop8p may result from degradation of pre-rRNAs by the exosome. These results strongly indicate that Nop8p may control exosome function during pre-rRNA processing.

<p>Cancer immunotherapy aims at reversing the immunosuppressive tumor environment and enhancing anti-tumor immunity. This thesis comprises studies on murine models for prostate (TRAMP-C2) and bladder (MB49) cancer with the aim to explore if the introduction of an adenoviral vector expressing CD40 ligand (AdCD40L) can induce anti-tumor immune responses.</p><p>We show in subcutaneous mouse models that AdCD40L treatment suppresses tumor growth. Bladder cancer is known to secrete immunosuppressive IL-10 which may inhibit T cell function. We show that introducing AdCD40L into mouse bladder tumors inhibits IL-10 production and reverses immunosuppression. AdCD40L-transduced mouse prostate cancer cells showed caspase activation and reduced cell viability. Vaccination with CD40L-modified prostate cancer cells induces anti-tumor responses and protects mice against rechallenge with native TRAMP-C2 cells. In order to enhance AdCD40L therapy, we explored the possibility of combining it with the histone deacetylase inhibitor FK228, also known as depsipeptide. We show that FK228 upregulates coxsackie and adenovirus receptor expression and thereby enhances adenoviral-mediated CD40L expression in both murine and human prostate cancer cells. Increasing amounts of FK228 or AdCD40L reduces prostate cancer cell viability, while the combined treatment gives at least an additive therapeutic effect. Moreover, we show that AdCD40L transduction of prostate cancer cells induces endogenous CD40 expression and sensitize them for CD40L-mediated therapy.</p><p>In order to conduct prostate-specific gene therapy, prostate-specific promoters can be used to drive transgene expression. However, there are no reports on prostate-specific promoters that are transcriptionally active in mouse cells. Here we show that by using the two-step transcription activation system (TSTA), we can enhance the activity of a recombinant human promoter sequence and obtain activity in mouse prostate cancer cells as well. This finding paves the way for future studies of prostate-specific gene therapy in immunocompetent mouse models.</p>

Cancer immunotherapy aims at reversing the immunosuppressive tumor environment and enhancing anti-tumor immunity. This thesis comprises studies on murine models for prostate (TRAMP-C2) and bladder (MB49) cancer with the aim to explore if the introduction of an adenoviral vector expressing CD40 ligand (AdCD40L) can induce anti-tumor immune responses. We show in subcutaneous mouse models that AdCD40L treatment suppresses tumor growth. Bladder cancer is known to secrete immunosuppressive IL-10 which may inhibit T cell function. We show that introducing AdCD40L into mouse bladder tumors inhibits IL-10 production and reverses immunosuppression. AdCD40L-transduced mouse prostate cancer cells showed caspase activation and reduced cell viability. Vaccination with CD40L-modified prostate cancer cells induces anti-tumor responses and protects mice against rechallenge with native TRAMP-C2 cells. In order to enhance AdCD40L therapy, we explored the possibility of combining it with the histone deacetylase inhibitor FK228, also known as depsipeptide. We show that FK228 upregulates coxsackie and adenovirus receptor expression and thereby enhances adenoviral-mediated CD40L expression in both murine and human prostate cancer cells. Increasing amounts of FK228 or AdCD40L reduces prostate cancer cell viability, while the combined treatment gives at least an additive therapeutic effect. Moreover, we show that AdCD40L transduction of prostate cancer cells induces endogenous CD40 expression and sensitize them for CD40L-mediated therapy. In order to conduct prostate-specific gene therapy, prostate-specific promoters can be used to drive transgene expression. However, there are no reports on prostate-specific promoters that are transcriptionally active in mouse cells. Here we show that by using the two-step transcription activation system (TSTA), we can enhance the activity of a recombinant human promoter sequence and obtain activity in mouse prostate cancer cells as well. This finding paves the way for future studies of prostate-specific gene therapy in immunocompetent mouse models.

Dietary factors may affect development and progression of prostate cancer. Experimental and epidemiological studies have suggested an effect of phytoestrogens on prostate cancer. Lignans are the predominant phytoestrogen in a Western diet. The effects of a diet rich in phytoestrogens and in particular lignans, as compared to a control diet, were assessed in several prostate cancer models. In paper I, 70 athymic nude mice with transplanted subcutaneous LNCaP tumours, an androgen sensitive human prostate cancer cell line, were fed one out of six phytoestrogen rich diets or a control diet after tumour injection. The rye diet, with high lignan content, decreased tumour take and growth, decreased secretion of prostate specific antigen and increased apoptosis. Addition of fat to the rye diet decreased the beneficial effects. In paper II, transgenic mice designed to develop prostate cancer (TRAMP) were fed rye bran or a control diet from the age of four weeks. Rye bran decreased prostate epithelial cell volume by 20%, and increased cell apoptosis by 31% as compared to the control diet. In paper III, we examined the effects of 7-hydroxymatairesinol (HMR), a purified lignan, in nude mice with subcutaneous LNCaP tumours in two different concentrations as compared to a control diet. Mice on the HMR diets had a reduced tumour take rate, lower total tumour volume, increased proportion of non-growing tumours, and increased apoptosis as compared to the control diet. Paper IV was a three week intervention study exploring the effects of rye bran bread vs. a control diet in men with prostate cancer. The men in the rye group had increased levels of plasma enterolactone and in biopsies from the prostate after the intervention an increase in apoptosis was observed in comparison with biopsies obtained before the intervention. In paper V, we examined the association between plasma levels of enterolactone, and risk of prostate cancer in a nested case control study. In the Northern Sweden Health and Disease Cohort, enterolactone concentrations were measured in plasma obtained at a mean time of 5 years before diagnosis from 265 cases of prostate cancer, and from 525 matched controls. We found no significant association between plasma enterolactone and risk of prostate cancer. Men with very low enterolactone levels (bottom decile) however, had significantly higher risk of prostate cancer. Phytoestrogen rich diet including soy, rye bran, substances purified from rye, and a purified lignan (HMR) all inhibited prostate tumour growth. However, it cannot be concluded that the effects observed were due solely to lignans as other components in rye grain such as tannins, phytic acid, ferulic acid, vitamins and minerals may have contributed to the beneficial effects. Thus, additional studies are needed to further elucidate the effects of phytoestrogens on prostate cancer development and progression.

Orientador: Ana Maria Pellegrini / Banca: Cynthia Yukiko Hiraga / Banca: José Angelo Barela / Resumo: A coordenação intermembros é exigida em inúmeras atividades motoras. Nestas atividades, os indivíduos precisam coordenar muitos componentes do corpo, mantendo relações entre eles e destes com o ambiente. Em um sistema dinâmico complexo, as relações entre as partes do sistema limitam ou influenciam o comportamento de outras partes, levando à emergência de padrões de coordenação. Crianças com Transtorno do Desenvolvimento da Coordenação (TDC) têm sido caracterizadas por apresentarem dificuldade em coordenar ritmicamente as partes do corpo em padrões específicos de coordenação intermembros. O presente estudo investigou a emergência e a estabilidade de padrões motores de crianças com TDC em uma tarefa rítmica de coordenação intermembros, analisando suas capacidades de sincronizar os deslocamentos dos membros superiores e inferiores em diferentes superfícies de apoio. Doze crianças com Desenvolvimento Típico (DT) e 12 crianças com TDC realizaram a tarefa de saltar e bater palma, durante 15 segundos, em duas superfícies: rígida (chão) e elástica (mini-trampolim). Foi solicitado à criança saltar e bater palma em quatro condições de coordenação: (i) de livre escolha do participante - Livre; (ii) batendo palma toda vez que os pés tocavam a superfície de apoio - Palma em Baixo; (iii) batendo palma toda vez que o corpo alcançava a máxima altura do salto - Palma em Cima; e (iv) batendo palma toda vez que os pés tocavam a superfície de apoio e toda vez que o corpo alcançava a máxima altura do salto - Duas Palmas. Quando a tarefa foi executada na condição Livre, os resultados mostraram que o padrão emergente das crianças com TDC foi diferente e mais variável na superfície mini-trampolim comparado com o das crianças com DT e com o delas mesmas na superfície chão. Além disso, na condição Palma em Baixo e Palma em Cima, as crianças... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Interlimb coordination is required in many motor activities. To perform these activities, people have to coordinate all body segments at the same time, keeping a relationship between segments and with the environment. In a complex dynamic system, the relationships between its parts limit or influence the behavior of other parts, so coordination patterns emerge. Children with Developmental Coordination Disorder (DCD) have been characterized by showing difficulty in rhythmically coordinate body segments, in specific interlimb coordination patterns. The purpose of this study was to investigate the emergency and stability of coordination patterns in children with DCD when they perform a rhythmic interlimb coordination task, analyzing their abilities to synchronize the movements of upper and lower limbs in two different surfaces. Twelve children with Typical Development (TD) and 12 children with DCD performed a jumping and clapping task during 15 seconds in two surfaces: rigid (on the floor) and elastic (on the mini-tramp). Children were required to clap while jumping (i) in their chosen pattern - Free; (ii) when the feet touched on the surface - Clapping-surface; (iii) when the body reached the maximum jumping height - Clapping-jumping; and (iv) when the feet touched the surface and when the body reached the maximum jumping height - Clapping-both. For the Free condition, the results showed that the DCD children emergent pattern was different and more variable on the mini-tramp than on the floor as compared with TD children coordination pattern. Furthermore, children with DCD were more variable in Clapping-surface and Clapping-jumping conditions compared with TD children. Clapping-jumping condition, characterized by relative phase of 180°, was more difficult for both DCD and TD children to perform than Clapping-surface condition, characterized by relative phase... (Complete abstract click electronic access below) / Mestre

Aluminium has great properties that are utilised the world over, but the production of primary aluminium is very energy intensive. In order to reduce the energy-cost, the aluminium can be recycled by re-melting aluminium scrap. This results in a circularity of the aluminium, as it is produced from ore to a metal and then the metal scrap can be re-melted again for other use.  The study also focuses on secondary production in Sweden. Through interviewing diverse actors in Sweden and analysing literature, an understanding of how the circulatory systems work was developed and the problems that can occur within it.  The major problems found is that through re-melting, the previous alloying elements can become impurities in the new scrap-based material. These impurities can change the properties in the aluminium. Separating these impurities from the aluminium is not an easy process, but a growing research question. Easiest is to minimise these contaminations, companies do this by sourcing where scrap is coming from and its compositional information, so to better organize or use the scrap for a similar purpose aluminium alloy.  This study looked at how the circulation of aluminium scrap works and how used scrap is once again returned to new reusable aluminium. With an understanding of how the processes it is easier to locate problems to improve the processes. / Aluminium har mycket goda mekaniska egenskaper som används i hela världen, men att producera primär aluminium är extremt energikrävande. För att minska energikostnaden kan man återvinna aluminiumet, det görs genom att återanvända gammalt aluminiumskrot. När man gör detta så leder det till ett cirkulärt kretslopp, där det börjar från malm som produceras till metall, när metallen blir till skrot så kan det återanvändas för att producera nytt aluminium.  Genom att intervjua folk inom branschen och att analysera litteratur inom ämnet, så skapades en förståelse hur det cirkulär kretsloppet fungerar och problem som kan uppstå inom systemet.  Det största problemet som hittades var att genom att återvinna aluminium skrot, så kan det tidigare legeringselement bli föroreningar i den nya skrot baserade materialet. Dessa föroreningarna kan ändra egenskaperna hos aluminiumet. För att får bort dessa föroreningar kan vara en svår process eller fortfarande utvecklande processen. Det är mycket lättare att försöka undvika dessa föroreningarnas från börja. Företagen gör detta genom att veta var skrotet kommer ifrån och skrotets legeringsämnen innan de återanvänder det. Då kan de organisera skrotet bättre och använda det till liknande skrot material i framtiden.  Denna studien fokuserar på hur skrotbaserat aluminium fungerar i ett kretslopp och hur gammalt skrot kan återanvändas till ny användbar aluminium. Med en förståelse på hur processen fungerar, så är det mycket lättare att hitta problem som kan leda till möjligheter att förbättra processen.