O consumo de energia se torna cada vez mais importante para a arquitetura de processadores, onde o número de cores dentro de um mesmo chip está aumentando mas o total de energia disponível se mantém no mesmo nível ou até mesmo se reduz. Assim, técnicas para economizar energia, tais como opções de escala de frequência e desligamento automático de subsistemas, estão sendo usadas para manter a troca entre energia e desempenho. Para se obter alto desempenho, os atuais Chip Multiprocessors (CMPs) integram grandes memórias cache a fim de reduzir a latência média para acesso a memória principal, através da alocação do conjunto de dados da aplicação dentro do chip. Essas memórias cache tem sido projetadas tradicionalmente para explorar a localidade temporal usando políticas de substituição inteligentes e localidade espacial buscando todos os dados da linha da cache após uma falta de dados. Entretanto, estudos recentes mostraram que o número de sub-blocos dentro da linha da memória cache, que são realmente usados, costuma ser baixo, sendo que, os sub-blocos que são usados recebem poucos acessos antes de se tornarem mortos (isto é, nunca mais são acessados). Além disso, muitas da linhas da memória cache permanecem ligadas por longos períodos de tempo, mesmo que os dados não sejam usados novamente ou são inválidos. Para linhas de cache modificadas, a memória cache aguarda até que a linha seja expulsa para que esta seja gravada (write-back) de volta no próximo nível de memória. Essas escritas competem com as requisições de leitura (demanda do processador e prébusca da cache), aumentando a pressão no controlador de memória. Por essas razões, a eficiência energética e o desempenho das memórias cache não são ideais. Essa tese propõe a aplicação de preditores de uso de linhas da cache para aumentar a eficiência energética das memórias cache. São propostos os mecanismos Dead Sub-Block Predictor (DSBP) e Dead Line and Early Write-Back Predictor (DEWP) para permitir economia de energia sem que haja degradação do desempenho. DSBP é usado para prever quais sub-blocos da linha da cache serão usados e quantas vezes eles serão acessados de forma a trazer para a cache apenas os sub-blocos úteis e desliga-los após eles serem acessados pelo número de vezes previsto. DEWP prevê linhas de cache mortas assim que elas recebem o último acesso, desligando essas linhas. As linhas sujas são escalonadas para sofrerem write-back após a última operação de escrita, aumentando o potencial de salvar energia, reduzindo também a pressão no controlador de memória. Ambos os mecanismos propostos também reduzem a poluição nas memórias cache, dando prioridade para a expulsão de linhas mortas, melhorando as atuais políticas de substituição. Embora cada mecanismo apresentado seja capaz de funcionar separadamente dentro do sistema, ambos os mecanismos podem também ser misturados em uma mesma hierarquia de cache. Essa implementação mista é interessante pois a granularidade de sub-bloco é preferível para níveis de cache próximos do processador, onde as linhas de memória cache são expulsas rapidamente, enquanto o último nível de cache tende a usar toda a linha antes da sua expulsão. Com o intuito de avaliar os mecanismos propostos, é apresentado o Simulator of Non- Uniform Cache Architectures (SiNUCA). Esse simulador de microarquitetura com precisão de ciclos é validado em termos de desempenho e consumo de energia através da comparação com um processador real. Os resultados de desempenho foram obtidos executando aplicações das cargas de trabalho single-threaded do conjunto SPEC-CPU2006 e aplicações multi-threaded dos conjuntos SPEC-OMP2001 e NAS-NPB. Os resultados relativos a energia foram obtidos integrando o SiNUCA com as ferramentas de modelagem Multi-core Power, Area, and Timing (McPAT) e CACTI. Quando aplicados os mecanismos em todos os níveis de memória cache, observou-se em média uma redução de 36% no consumo de energia usando o DSBP, 25% usando o DEWP e 37% quando usou-se o DSBP nos níveis L1 e L2 e o DEWP no último nível. Todas essas reduções causaram uma perda desprezível de desempenho de menos de 4% em média. / Energy consumption is becoming more important for processor architectures, where the number of cores inside the chip is increasing and the total power budget is kept at the same level or even reduced. Thus, energy saving techniques such as frequency scaling options and automatic shutdown of sub-systems are being used to maintain the trade-off between power and performance. To deliver high performance, current Chip Multiprocessors (CMPs) integrate large caches in order to reduce the average memory access latency by allocating the applications’ working set on-chip. These cache memories have traditionally been designed to exploit temporal locality by using smart replacement policies, and spatial locality by fetching entire cache lines from memory on a cache miss. However, recent studies have shown that the number of sub-blocks within a line that are actually used is often low, and those sub-blocks that are used are accessed only a few times before becoming dead (that is, never accessed again). Additionally, many of the cache lines remain powered for a long period of time even if the data is not used again, or is invalid. For modified cache lines, the cache memory waits until the line is evicted to perform the write-back to next memory level. These write-backs compete with read requests (processor demand and cache prefetch), increasing the pressure on the memory controller. For these reasons, the energy efficiency and performance of cache memories are not ideal. This thesis introduces cache line usage predictors to increase the energy efficiency of cache memories. We propose the Dead Sub-Block Predictor (DSBP) and Dead Line and Early Write-Back Predictor (DEWP) mechanisms to enable energy savings without performance degradation. DSBP is used to predict which sub-blocks of a cache line will be actually accessed and how many times they will be used in order to bring into the cache only those sub-blocks that are necessary, and power them off after they are accessed the predicted number of times. DEWP predicts dead lines as soon as they receive the last access, and turns off these lines. Dirty lines are scheduled for write-back after the last write operation occurs, increasing the energy savings potential and also reducing the pressure on the memory controller. Both proposed mechanisms also reduce pollution in cache memories by prioritizing dead lines for eviction in the existing replacement policy. Although each introduced mechanism is capable of performing separately inside a system, both mechanisms can also be mixed in the same cache hierarchy. This mixed implementation is interesting because the sub-block granularity is more suitable for cache levels closer to the processor, where the cache lines are quickly evicted, while the Last- Level Cache (LLC) tends to use the whole cache line before its eviction. In order to evaluate our proposed mechanisms, we introduce the Simulator of Non- Uniform Cache Architectures (SiNUCA). This cycle-accurate microarchitecture simulator is validated in terms of performance and energy consumption by comparing it to a real processor. Our performance results were obtained executing single-threaded applications from SPEC-CPU2006 and multi-threaded applications from SPEC-OMP2001 and NASNPB benchmark suites. The energy related results were obtained by integrating SiNUCA with the Multi-core Power, Area, and Timing (McPAT) framework and the CACTI power modeling tool. When applying our mechanisms on all the cache levels, we observe on average a 36% energy reduction for DSBP, 25% energy reduction using DEWP and an average reduction of 37% in the energy consumption applying DSBP on L1 and L2 and DEWP on the LLC. All these reductions caused a negligible performance loss of less than 4% on average.

Made available in DSpace on 2017-06-01T18:18:37Z (GMT). No. of bitstreams: 1 eneida_roselia_nascimento_silva.pdf: 1309092 bytes, checksum: eb6d9272ee6dba6f967d2bb52872a84f (MD5) Previous issue date: 2016-11-18 / This study aims to verify the (im) possibility of alienation of the fundamental right to the body under the central focus of surrogacy or solidarity belly, addressing the need or not to build a specific regulatory system. To do so will be raised studies on how the possibility of alienation of a fundamental right takes place within our society with the financial goal, disregarding often ethical, moral, legal and social values, often making women vulnerable against current bioethical developments. data and documents will be presented in order to verify that the current regulations in Brazil is sufficient for effective control of body disposal of possibility in cases of surrogacy. Depending on the technical procedures to work, the research involved literature, consisting primarily analysis of books, journal articles and materials available on the Internet; documentary, with analysis of Brazilian legislation and other countries, about the surrogacy. The method used is the inductive which is based on observation of particular facts and realities notes the existence of disposal of cases across the board. The search result has the function to inform on the need for a mechanism to force Act in order to make more effective and efficient control over these technological advances that grow increasingly in our society. / O presente estudo tem a finalidade de verificar a (im) possibilidade de alienação do direito fundamental ao corpo sob o enfoque central da maternidade de substituição ou barriga solidária, abordando a necessidade ou não de construção de um sistema regulatório específico. Para tanto, foram levantados estudos sobre de que maneira essa possibilidade de alienação de um direito fundamental ocorre dentro de nossa sociedade com o objetivo financeiro, desconsiderando, muitas vezes, valores éticos, morais, legais e sociais, tornando, muitas vezes, as mulheres vulneráveis frente à evolução bioética atual. Apresentaram-se dados e documentos com o objetivo de verificar se a regulamentação existente no Brasil é suficiente para o efetivo controle da possibilidade de alienação do corpo nos casos de maternidade de substituição. Consoante aos procedimentos técnicos ao trabalho, a pesquisa envolveu pesquisa bibliográfica, constituída basicamente de análise de livros, artigos de periódicos e material disponibilizado na internet; documental, com análise de legislação brasileira e de outros países, acerca da maternidade de substituição. O método utilizado foi o indutivo, fundamentado na observação de fatos de realidades particulares, constatando-se a existência de casos de alienação de forma generalizada. O resultado da pesquisa tem a função de informar sobre a necessidade de um mecanismo com força de Lei, de modo a tornar mais efetivo e eficiente o controle sobre esses avanços tecnológicos que crescem cada vez mais em nossa sociedade.

Congenital heart defects (CHDs) constitute a major proportion of clinically significant birth defects and are an important component of pediatric cardiovascular disease. Atrioventricular septal defects (AVSDs) include a range of anomalies characterized by atrial, ventricular, and atrioventricular (AV) valve defects. AVSDs commonly occur in the presence of a syndrome, most frequently Down syndrome; they also occur in isolation and are referred to as non-syndromic AVSDs (NSAVSDs). These studies were performed to evaluate for presence of an intermediate phenotype in parents and siblings of a child with a NSAVSD, risk factors associated with NSAVSDs, and prognostic risk factors for left AV valve replacement following primary repair of an AVSD. It was shown that the mean body surface area-standardized AV septal length (AVSL) was significantly shorter in the NSAVSD parents and siblings than in parents and siblings of syndromic AVSD case and control children. Using age- and gender-adjusted body surface area-standardized AVSL, it was determined that there was evidence for two component distributions in parents and siblings of NSAVSD children, suggesting the presence of an intermediate. Broadening the definition of AVSD to include those with a shortened AVSL may increase the power of genetic association and mapping studies to identify susceptibility genes. Risk factors associated with NSAVSD were examined using the 1997-2005 National Birth Defects Prevention Study database. Mothers who actively smoked or were exposed to passive smoke anytime from one month prior to pregnancy through the end of the first trimester were more likely to have an infant with a NSAVSD. There was a suggestive association between AVSDs and use of antibacterial, antifungal, and antiviral medications. Additional investigations are warranted to investigate associations with specific medications as well as to uncover possible gene-environment interaction effects that may modify these risks in order to develop improved primary prevention strategies. Using the Pediatric Cardiac Care Consortium database, factors associated with time to first reoperation and time to replacement following primary AVSD repair were evaluated. Type of AVSD repair, closure of the mitral valve cleft, moderate to severe postoperative left AV valve regurgitation, and presence of postoperative complete heart block were associated with earlier time to reoperation after adjusting for age and weight at AVSD repair. Down syndrome and presence of postoperative mitral stenosis were associated with earlier time to replacement. Prognostic risk factors following left AV valve replacement in children who had previously undergone AVSD repair were also identified. A prosthetic valve size to body weight ratio of greater than 3 and the presence of Down syndrome were identified as predictors of in-hospital death following left AV valve replacement. By adding to our knowledge of the AVSD familial and environmental risk factors from these studies, we will be able to (1) improve genetic counseling, (2) identify other family members for genetic testing, (3) begin to devise primary prevention strategies, and (4) improve treatment modalities. By recognizing prognostic factors which influence survival, optimal patient care can be devised which will not only improve treatment modalities, but also long-term survival.

Les maladies lysosomales forment un groupe hétérogène d’une cinquantaine d’affections qualifiées de « rares ». Actuellement, seulement 9 maladies lysosomales disposent d’un traitement spécifique, principalement par enzymothérapie substitutive, mais les effets bénéfiques sont souvent limités. Le manque de ciblage pour le Récepteur du Mannose 6-Phosphate (RM6P), responsable de l’internalisation dans les lysosomes, expliquerait en partie cette efficacité modérée des enzymes thérapeutiques. Dans ce contexte, nous avons développé une approche de ciblage innovante basée sur des Analogues synthétiques du Mannose 6-Phosphate fonctionnalisés sur l’Aglycone (appelés AMFA) afin de répondre aux besoins non satisfaits par les traitements actuels.Les travaux de cette thèse portent principalement sur la maladie de Pompe, myopathie causée par la déficience d’une enzyme lysosomale, l’Alpha Glucosidase Acide (GAA), responsable de la conversion du glycogène en glucose. Afin d’améliorer l’adressage de l’enzyme thérapeutique aux lysosomes via le RM6P, nous avons fonctionnalisé la GAA recombinante humaine (rhGAA) avec les AMFA. Nos études sur la forme adulte de la maladie ont démontré une augmentation significative de l’internalisation et pour la première fois, chez des souris âgées modèles de la maladie, une restauration de la santé musculaire et une amélioration significative de la fonction motrice ont été observées (article 1). Nous nous sommes ensuite intéressés aux propriétés de la rhGAA-AMFA. Nous avons démontré que l’efficacité de la rhGAA-AMFA n’était pas uniquement due à une meilleure internalisation mais également à une meilleure maturation intracellulaire de l’enzyme (article 2). En effet, nos résultats ont démontré que chez les patients atteints de la maladie de Pompe, il existe une surexpression des phosphatases acides ACP2 et ACP5. Ces phosphatases peuvent détruire le signal mannose 6-phosphate (M6P) naturellement présent sur l’enzyme, ce qui interrompt sa maturation en forme active. L’AMFA, contrairement au M6P, est insensible à cette dégradation et assure donc la stabilité de l’adressage de l’enzyme in vitro, mais également in vivo.L’ensemble de ces résultats suggèrent que le greffage des AMFA sur des enzymes recombinantes représente une nouvelle solution thérapeutique pour le traitement de la maladie de Pompe et potentiellement pour le traitement d’autres maladies lysosomales. / Lysosomal diseases form a heterogeneous group of about fifty rare diseases. At present, only 9 lysosomal diseases have a specific treatment, mainly by enzyme replacement therapy but the beneficial effects appear often limited. The lack of targeting for the Mannose 6-Phosphate Receptor (M6PR), responsible for internalization into the lysosomes, would partly explain this moderate efficiency of the therapeutic enzymes. In this context, we have developed an innovative targeting approach based on Mannose 6-Phosphate Synthetic Analogues Functionalized at the Aglycone position (called AMFAs) to address the unmet needs of current treatments.The work of this thesis focuses mainly on Pompe disease which is a myopathy caused by the deficiency of a lysosomal enzyme, Acid Alpha Glucosidase (GAA), responsible for the conversion of glycogen into glucose. In order to improve the targeting of the therapeutic enzyme to lysosomes via the M6PR, we have functionalized the human recombinant GAA (rhGAA) with the AMFAs. Our studies on aged mice model of the adult form of the disease have demonstrated a significant increase of the enzyme internalization and for the first time, the restoration of muscle health and the significant improvement in motor function (article 1). We then investigated the properties of rhGAA-AMFA. We have proved that the effectiveness of rhGAA-AMFA is not only due to a better cell uptake but also to a more complete intracellular processing of the enzyme (article 2). Indeed, our results demonstrated that in myoblasts of patients affected by Pompe disease there is an overexpression of ACP2 and ACP5 acid phosphatases. These phosphatases can destroy the mannose 6-phosphate signal (M6P) naturally present on the enzyme, therefore possibly interrupting its processing into the active form. AMFA, unlike M6P, is insensitive to this degradation and thus ensures the stability of enzyme addressing in vitro, but also in vivo.All together, these results suggest that the grafting of the AMFAs on recombinant enzymes represents a new therapeutic solution for the treatment of Pompe disease and potentially for other lysosomal diseases.

This study, that is a research and product development process, is based on sustainable development and the negative impacts of the growing consumption, and wear-and-tear habits of today’s society. The way we handle our resources, from mine to landfill cause devastating effects on the climate. LAST, is a multi-functional table made from wooden waste materials, that represents product design that allows the user to build a strong, long-lasting relationship with the product. The table is versatile, allows easy dismantling and incorporates qualities that create an incentive for the user to build an attachment to it to increase its lifetime. This has been done through applying different strategies within emotional design, product attachment and design for sustainability as well as applying knowledge within timeless design, aesthetic nourishment. The Japanese philosophy of Wabi Sabi has acted as inspiration to help navigate the projects design proposal that could allow for the user to appreciate their product for longer and indorse product longevity. The research question for the study is as follows: How can you promote product longevity by means of product design for sustainable development?

The diploma thesis deals with possibilities and subsequent proposal of individual measures to achieve the reduction of energy intensity in the company fischer Vyškov, s.r.o. At the beginning of the thesis is the analysis of the current state of the areas on which the work is further focused. These include the production of compressed air, cooling technology and lighting. The main cost-saving measures for the production of compressed air is a proposal to purchase a new compressor. For cooling, there are free cooling options, including the design of a dry cooler and its inclusion in the cooling circuit. The last part is the design of a new lighting system using LED lamps.

This diploma thesis deals with an experimental analysis of lubrication of total hip joint replacement using fluorescence microscopy, focusing on so-called soft bearing pairs. Experiments were realized using a hip joint simulator, which was modified and refined for fluorescence microscopy. The aim of this diploma thesis was to determine the effect of the individual components of the synovial fluid on the lubrication mechanisms. For this purpose, different model fluids were designed to represent the composition of proteins and other synovial fluid constituents to elucidate the effect of albumin, -globulin and hyaluronic acid on the resulting lubrication performance. The experiments were separate into two categories different in type of load, dynamic (representative walking) and combined (representing standing with short walk). The experimental results were time-dependent fluorescence intensity values, representing dimensionless film thickness parameters. The values were recorded on the graphs and supplemented with fluorescence images taken during the characteristic sections of the measurements. The measured data was subsequently confronted with previously published articles. It was found that the dominant constituent responsible form film thickness is albumin, while -globulin and hyaluronic acid forms thin stable layer enhancing adsorption ability of albumin which contributes to increase of film thickness eventually.

The aim of this diploma thesis is a rehabilitation study of the sewer network on Vídeňská street in the city of Brno. The first part of the thesis includes an accompanying review including basic data about the sewage gutter, including the characteristics of the affected area with a detailed description of the geological and hydrogeological rates. This is followed by a technical review, which consists of hydrotechnical calculations and overal summary of the construction-technical condition. The subject of the following part is a proposal and description of several varying solutions for the rehabilitation, including, particularly, trenchless technologies. Further on, all of the proposed variants are evaluated based on technical, economical and environmental impact. Finally, all the observations are summarized and a final recommendation for the way of solving the rehabilitation is carried out.

Cílem této diplomové práce je navrhnout peristaltické čerpadlo pro hemodialýzu s ohledem na minimalizaci tlakových pulzací. Pomocí analytické analýzy je navržen nový koncept redukce tlakových pulzací, který využívá zrychlení k navýšení tlaku v prostoru mezi válečky. Fungování peristaltického čerpadla je simulováno pomocí programu Ansys Fluent pro získání lepší představy o proudění v čerpadle. Souběžně s návrhem nového konceptu bylo navrženo více tradiční čerpadlo, které bylo následně vyrobeno a experimentálně odzkoušeno. Data získaná z experimentu mohou být dále použita pro nový koncept.

This diploma thesis is focused on dental materials used in prosthetic medicine. In the introduction, the most important characteristic of dental materials is summarised, which is biocompatibility. Further it contains distribution of nowadays used dental materials, which are oxidic ceramics and titanium alloys. It describes pitfalls of machining of those materials. Final part is devoted to process of the production of the new dental crown, from the first arrival of the patient to the machining of final product. The thesis also compares the economics of dental crown production using milling and 3D printing.