Low latency reconfiguration mechanism for fine-grained processor internal functional units

The strive for performance, low power consumption, and less chip area have been diminishing the reliability and the time to fault occurrences due to wear out of electronic devices. Recent research has shown that functional units within processors usually execute a different amount of operations when running programs. Therefore, these units present different individual wear out during their lifetime. Most existent schemes for re-configuration of processors due to fault detection and other processor parameters are done at the level of cores which is a costly way to achieve redundancy. This paper presents a low latency (approximately 1 clock cycle) software controlled mechanism to reconfigure units within processor cores according to predefined parameters. Such reconfiguration capability delivers features like wear out balance of processor functional units, configuration of units according to the criticality of tasks running on an operating system and configurations to gain in performance (e.g. parallel execution) when possible. The focus of this paper is to show the implemented low latency reconfiguration mechanism and highlight its possible main features

Real-time dynamic hardware reconfiguration for processors with redundant functional units

The tiny logic elements in modern integrated circuits increase the rate of transient failures significantly. Therefore, redundancy on various levels is necessary to retain reliability. However, for mixed-criticality scenarios, the typical processor designs offer either too little fault-tolerance or too much redundancy for one part of the applications. Amongst others, we specifically address redundant processor internal functional units (FU) to cope with transient errors and support wear leveling. A real-time operating system (RTOS) was extended to control our prototypical hardware platform and, since it can be configured deterministically within few clock cycles, we are able to reconfigure the FUs dynamically, at process switching time, according to the specified critically of the running processes. Our mechanisms were integrated into the Plasma processor and the Plasma-RTOS. With few changes to the original software code, it was, for example, possible to quickly change from fault-detecting to fault-correcting modes of the processor on demand

Pan-cancer analysis of the metabolic reaction network

Metabolic reprogramming is considered a hallmark of malignant transformation. However, it is not clear whether the network of metabolic reactions expressed by cancers of different origin differ from each other or from normal human tissues. In this study, we reconstructed functional and connected genome-scale metabolic models for 917 primary tumor samples across 13 types based on the probability of expression for 3765 reference metabolic genes in the sample. This network-centric approach revealed that tumor metabolic networks are largely similar in terms of accounted reactions, despite diversity in the expression of the associated genes. On average, each network contained 4721 reactions, of which 74% were core reactions (present in >95% of all models). Whilst 99.3% of the core reactions were classified as housekeeping also in normal tissues, we identified reactions catalyzed by ARG2, RHAG, SLC6 and SLC16 family gene members, and PTGS1 and PTGS2 as core exclusively in cancer. These findings were subsequently replicated in an independent validation set of 3388 genome-scale metabolic models. The remaining 26% of the reactions were contextual reactions. Their inclusion was dependent in one case (GLS2) on the absence of TP53 mutations and in 94.6% of cases on differences in cancer types. This dependency largely resembled differences in expression patterns in the corresponding normal tissues, with some exceptions like the presence of the NANP-encoded reaction in tumors not from the female reproductive system or of the SLC5A9-encoded reaction in kidney-pancreatic-colorectal tumors. In conclusion, tumors expressed a metabolic network virtually overlapping the matched normal tissues, raising the possibility that metabolic reprogramming simply reflects cancer cell plasticity to adapt to varying conditions thanks to redundancy and complexity of the underlying metabolic networks. At the same time, the here uncovered exceptions represent a resource to identify selective liabilities of tumor metabolism

Advancing CRISPR technologies to engineer yeast metabolism

The advent of genetic engineering tools has initiated an era of manipulating microorganisms for the production of valuable compounds for our society. Precise engineering of these microbes commonly requires introducing genetic modifications such as gene deletion, overexpression, and accurate regulation in order to enhance the production of the compound of interest. In this context, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 technology, adapted from the prokaryotic adaptive immune system, has revolutionized our ability to manipulate a broad range of living organisms. In contrast to other methods, this technology works like a molecular pair of scissors (Cas9) which is guided by a programmable RNA (gRNA) molecule binding at a specific location in the DNA. The programmability and time-efficiency offered by this technology have in the recent years been successfully exploited in rewiring the metabolic network to enhance the production of metabolites used in various areas of industrial biotechnology. \ua0In this thesis, I present several studies applying the technological diversity provided by CRISPR in the context of building efficient yeast cell factories for the production of oleochemicals -sustainable substitutes for plant derived lipids. Since oleochemicals derive from lipid products, the main engineering strategies presented essentially focus on fatty acid metabolism and its precursors. First, we exploited CRISPR/Cas9 endonuclease capacity to extensively remodel yeast lipid metabolism. We showed that the disruption of several metabolic fluxes allows to overcome the main limiting steps in fatty acid biosynthesis and favors the production of free fatty acids and triacylglycerols, two important precursors for the production of oleochemicals. Second, we harnessed the ability to precisely regulate genes using the catalytically deactivated form of the Cas9 protein (dCas9) coupled to transcription factors for fine-tuning the expression of genes involved in lipid biogenesis. Additionally, we proposed a framework for dCas9-based applications based on computational techniques for predicting key genes potentially favoring the production of yeast endogenous metabolites. Finally, we expanded the CRISPR repertoire by building new tools to accelerate yeast cell factory design. We exploited a Type I CRISPR-associated endoribonuclease for multiplex genome engineering and transcriptional regulation via processing an RNA transcript into multiple gRNAs, and we developed a computational tool for designing gRNAs targeting multiple loci at once. In summary, the work presented in this thesis provides various ways to efficiently engineer yeast metabolism by exploiting the diversity of CRISPR technologies, as well as new tools to the community for future engineering strategies

Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion

Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid activation genes (the first step in β-oxidation), main storage lipid formation genes, and phosphatidate phosphatase genes resulted in a constrained lipid metabolic network in which fatty acid flux was directed to a large extent toward phospholipids. This resulted in simultaneous increases of phospholipids by up to 2.8- fold and of FFAs by up to 40-fold compared with wild-type levels. Further deletion of phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and 105% increase in phospholipid levels, suggesting that phospholipid hydrolysis plays an important role in FFA production when phospholipid levels are increased. The multiple deletion mutant generated allowed for a study of fatty acid dynamics in lipid metabolism and represents a platform strain with interesting properties that provide insight into the future development of lipid-related cell factories

Do poeta-crítico ao poeta-teórico: a poiesis amazônica na escritura literária de Paes Loureiro

O presente trabalho propõe-se a discutir acerca da poética amazônica formulada pelo poeta, professor e ensaísta paraense João de Jesus Paes Loureiro, para ser mais preciso, elenca-se aqui não apenas a produção de poesia do citado escritor, mas também os escritos ensaísticos de íntima relação com o processo criativo manifesto por este artista. Assim, é com base nos volumes I e II (Poesia), III (Ensaios) e IV (Produção Acadêmica) das Obras reunidas (2000) de Paes Loureiro que tal tarefa hermenêutica-reflexiva far-se-á aqui possível. Com isso, analisar o fazer poético deste autor enquanto uma transmutação do universo real amazônico ao ambiente ficcional proposto pela arte da palavra, intenta ao conteúdo formal e temático de sua poesia uma real “encantaria da linguagem”, onde um mundo mítico transcende-se ao material linguístico, compondo assim uma mitopoética devaneante da cultura amazônica, fruto de suas reflexões sobre poiesis. Para isso, serão de grande contribuição as reflexões de Maurice Blanchot (2005) sobre o espaço literário, os apontamentos de Gilles Deleuze (1992) acerca da escritura, bem como os fundamentos de Gaston Bachelard (1997) no que diz respeito ao devaneio e imaginação

O novo Brasil, uma nova superpotência?

TCC (Graduação) - Universidade Federal de Santa Catarina. Centro Socioeconômico. Curso de Graduação em Relações Internacionais.Desde a explosão da crise em 2008, as conhecidas Grandes Potências vêm apresentando sinais de recessão econômica, o que vem aumentando o descontentamento da população interna e as críticas ao modelo capitalista atual. Neste mesmo cenário de crise está inserido o Brasil que até o ano de 2012 não havia sofrido muito com a crise. Como muito se ouviu falar na mídia, o Brasil foi um dos últimos países a entrar na crise, e também um dos primeiros a sair dela. Precedendo esse cenário, no desenrolar da década de 1990 mais especificamente, uma conjuntura mais multilateral veio se materializando no sistema internacional. A partir da primeira metade da década 2000, essa tendência intensificou-se, tornando a estrutura de poder internacional mais democrática. Simultaneamente ao referido fenômeno, um conjunto de fatores internos possibilitou que o Brasil focasse seus esforços em termos de política externa para a busca de uma maior inserção internacional. Alguns resultados foram obtidos. A maior proeminência brasileira nos últimos anos vem sendo exaltada pela mídia internacional, com bastante otimismo. Termos como superpotência, Grande Potência, gigante sul americano, entre outros; têm sido utilizados constantemente para definir a nova atuação do país, no contexto do século XXI. Contudo, a história brasileira demanda uma reflexão mais profunda, com o intuito de tentar responder à duvida latente: se realmente o “eterno país do futuro” tem trilhado o trajeto certo na tentativa de conquistar seu eterno tradicional sonho de tornar-se potência. O presente trabalho propõe-se a uma apreciação dessa nova conjuntura internacional, bem como dos fatores que possibilitaram a tão mencionada maior atuação internacional do país. Como foco de pesquisa, pretende-se investigar qual o atual posicionamento do país na estrutura de poder das relações internacionais. Terá ele se tornado uma grande potência? Ou todo esse alvoroço não passa de mais um capítulo efêmero do tradicional sonho brasileiro de se tornar potência?Since the eruption of the crisis in 2008, the countries known as Great Powers are showing signs of economic recession, which has been growing discontent of the populations and provoking criticism of the current capitalist model. In this same scenario is inserted Brazil that until the year 2012 had not suffered much from the crisis. Media constantly treated Brazil as one of the last countries to enter the crisis and also one of the first to come out of it. A previous to the crisis one, more specifically in the 1990s, an environment more multilateral came unfolding in the international system. From the first half of the 2000s, this trend has intensified, making the international power structure more flexible. Simultaneously, a set of internal factors allowed Brazil to focus its foreign policy to seek greater international insertion. Some results were obtained. This greater Brazilian prominence in recent years has been highlighted by the international media, with plenty of optimism. Terms like Superpower, Great Power, the South American giant, among others, have been used consistently to define this new Brazil raise in the XXI century. However, the Brazilian history begs us a deeper reflection to try to answer if the "eternal country of the future" has found the right path to achieve their evergreen dream of becoming world power. This research will focus on making an evaluation of this new international environment, as well as the factors that led to this country's largest international performance. As a focus of research, it proposes to investigate the country's current position in the world power structure. It will try to answer the following question, has Brazil become a great power? Or all this speculations are just another ephemeral chapter of the eternal Brazilian dream of becoming a global power

Clonagem de genitores pisifera e proteômica diferencial durante a aquisição de competência embriogênica em palma de óleo (Elaeis guineensis Jacq.)

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Botânica, Programa de Pós-Graduação em Botânica, 2017.O presente trabalho objetiou avaliar respostas de genitores Pisifera de dendezeiros (Elaeis guineensis Jacq.) quanto à capacidade de regeneração de plantas por embriogênese somática (ES), além de identificar proteínas envolvidas durante o processo de aquisição de competência embriogênica em híbridos Tenera contrastantes para a embriogênese somática. Num primeiro experimento, explantes foliares de quatro genótipos adultos de dendezeiro da variedade Pisifera (A251424, A251427, A251512 e A251513) foram submetidos à indução de ES utilizando-se o meio de indução (MI), composto pelos sais e vitaminas de Murashige e Skoog (MS), suplementado com 30 g.L-1 de sacarose, 0,5 g.L-1 de glutamina, 0,5 g.L-1 de caseína hidrolisada, 2,5 g.L-1 de carvão ativado, 450 µM de Picloram e gelificado com 2,5 g.L-1 de phytagel. O material permaneceu nesta condição por 360 dias, com subcultivos a cada 150 dias. Posteriormente, o material foi transferido para o meio de multiplicação de calos (MM), composto por 40 µM de Picloram, 10 µM de 2-isopenteniladenina (2iP) e 2,5 g.L-1 de phytagel, onde permaneceu por mais 90 dias. Em seguida, os calos foram colocados em meio de diferenciação (MD) formado por 12,3 µM de 2iP, 0,54 µM de ácido naftalenoacético (ANA) e de 2,5 g.L-1 de phytagel. Depois de diferenciados, os embriões somáticos foram transferidos para o meio de regeneração, desprovido de reguladores de crescimento e acrescido de 2,5 g.L-1 de phytagel e carvão ativado. Durante todo o processo, o material foi avaliado morfo e histoquimicamente para melhor caracterizar as etapas. Num segundo experimento, a proteômica diferencial de dois híbridos Tenera var. B351733 (responsivo à ES) e var. B352933 (não-responsivo à ES) foi avaliada durante o processo inicial (14 dias) e tardio (150 dias) da aquisição de competência embriogênica em dendezeiro, etapas caracterizadas pelo início de formação de calo primário e calo embriogênico, respectivamente. As proteínas extraídas foram quantificadas por Bradford e analisadas por eletroforese bidimensional (2-DE). Proteínas consideradas diferenciais pelo programa de análise de imagem Image Master Platinum foram identificadas por espectrometria de massa. A sequência foi obtida no banco NCBI por meio do GI (Gene Identifier) de cada proteína identificada nestes tempos. Com as sequências, adicionalmente foi realizada a anotação funcional destas proteínas nas plataformas AgBase e Revigo, sendo o gene onthology (GO) de cada proteína obtido. A partir dos dados também foram gerados gráficos dos processos biológicos em cada tempo. Verificou-se que o genótipo Pisifera A251424 foi o mais responsivo ao processo de ES quando comparado aos demais, com maior formação de calos ao longo do tempo (45%). Na etapa MM, calos com até 10,6 mg de massa fresca foram os que apresentaram maior incremento de biomassa em relação aos calos de maior peso inicial. Com 90 dias em meio MD, calos embriogênicos se diferenciaram em embriões somáticos e até 130 dias após, clusteres de embriões somáticos surgiram nesta condição. Nas análises morfo-anatômicas e histoquímicas, quatro tipos de calos foram observados na etapa MI, sendo o nodular amarelado, com maior adensamento de amido nesta etapa, o único a progredir até a formação de embriões somáticos. Na análise proteômica das variedades Tenera, 52 proteínas diferencialmente abundantes no tempo 14 dias foram reveladas, incluindo 17 proteínas aumentadas e 14 diminuídas no genótipo responsivo, em relação ao genótipo não-responsivo. Já aos 150 dias de indução, 74 proteínas reguladas foram detectadas, incluindo 19 aumentadas e 13 diminuídas no genótipo responsivo em relação ao não-responsivo. Um total de 40 proteínas exclusivas foram observadas no genótipo responsivo aos 150 dias de indução, enquanto que o genótipo não-responsivo apresentou somente duas. A anotação funcional evidenciou uma menor diversidade dos processos biológicos aos 14 dias para o genótipo responsivo, e aos 150 dias estes processos apresentaram maior diversidade, quando comparados ao não-responsivo. A análise 2-DE e ontologia gênica permitiram a identificação de dez proteínas importantes relacionadas com a aquisição de competência embriogênica, entre elas a isoenzima catalase 2 (spot 254), mono-dehidro-ascorbato-redutase isoforma cloroplástica X2 (spot 150), subunidade beta da pirofosfatofrutose-6-fosfato-1- fosfotransferase (spot 338). De modo geral, os resultados obtidos envolvendo a ES, morfoanatomia, histoquímica e a análise proteômica, aliada à bioinformática (anotação funcional), permitiram compreender melhor a propagação in vitro em dendezeiro, dando novos subsídios para pesquisas futuras rumo a um melhor entendimento sobre os processos de propagação clonal da espécie por embriogênese somática.The objective of this work was to evaluate the responses of the Pisifera genus of oil palm (Elaeis guineensis Jacq.) regarding the acquisition of embryogenic competence and plant regeneration by somatic embryogenesis (SE) and to identify proteins involved in the process of acquisition of embryogenic competence in Tenera hybrids contrasting as to the embryogenic capacity. In a first experiment, leaf explants of four adult genotypes of oil palm of the Pisifera variety (A251424, A251427, A251512 and A251513) were used for SE induction using the induction medium (IM) composed of salts and vitamins of Murashige e Skoog (MS) and supplemented with 30 gL-1 of sucrose, 0.5 gL-1 of glutamine, 0.5 gL-1 of hydrolyzed casein, 2.5 gL-1 of activated charcoal, 450 μM of Picloram and solidified with 2.5 gL-1 of phytagel. The material remained in this condition for 360 days, being subcultured every 150 days. Subsequently, the material was transferred to calluses multiplication medium (MM) containing 40 μM of Picloram, 10 μM of 2-isopentenyladenine (2iP) and 2.5 gL -1 of phytagel, where it remained for 90 days. Then, calluses were transferred to differentiation medium (DM), composed of 12.3 μM 2iP, 0.54 μM of naphthaleneacetic acid (ANA) and 2.5 gL-1 of phytagel. After differentiation, the somatic embryos were transferred to regeneration medium, without growth regulators and supplemented with 2.5 g.L-1 of phytagel and activated charcoal. Throughout the process, the material was evaluated morphologically and histochemically to better characterize the steps. In a second experiment, differential proteomics of two hybrids of the Tenera variety, B351733 (responsive to SE) and B352933 (non-responsive to SE) were evaluated during the initial (14 days) and late (150 days) process of the acquisition of embryogenic competence in oil palm, steps characterized by the beginning of formation of primary and embryogenic callus, respectively. Proteins extracted were quantified by Bradford assay and analyzed by two-dimensional electrophoresis (2-DE). Differential proteins detected by the Image Master Platinum software were identified by mass spectrometry. The sequence was obtained from NCBI bank by means of the GI (Gene Identifier) of each protein identified at these times. With the sequences, it was performed the functional annotation of these proteins on the AgBase and Revigo platforms, and the gene onthology (GO) of each protein was obtained. The graphics for biological process ES were generated for both genotypes at each time. It was verified that the Pisifera genotype A251424 was the most responsive to the SE process when compared to the others, because it presented greater calluses formation over time (45%). In stage MM, calluses with lower initial weight (up to 10.6 mg) presented a greater increase of fresh biomass in relation to the calluses of greater initial weight. After 90 days on MD medium, embryogenic calluses differentiated into somatic embryos and after 130 days, clusters of somatic embryos appeared on this condition. In the morpho-anatomical and histochemical analyzes, four types of calluses were observed in stage MI, being nodular yellowish with greater starch deposition in this step and proceeded in the stages until formation of somatic embryos. At the proteomic analysis of the Tenera varieties, 52 differentially abundant proteins on time 14 days were revealed, including 17 proteins increased and 14 decreased in the responsive genotype with respect to the non-responsive genotype. Already at 150 days of induction, 74 regulated proteins were detected, including 19 increased and 13 decreased also in the responsive genotype with respect to non-responsive genotype. A total of 40 unique proteins were observed in the responsive genotype at 150 days of induction, while the non-responsive genotype showed only two. The 2-DE analysis and gene ontology allowed the identification of ten important proteins related to the acquisition of embryogenic competence, among them Catalase isozyme 2 (spot 254), Monodehydro ascorbate reductase chloroplastic isoform X2 (spot 150), Pyrophosphatefructose-6-phosphate-1-phosphotransferase subunit beta like (spot 338). In general, the results obtained involving SE, morphology, histochemistry and proteomic analysis, together with bioinformatics (functional annotation), allowed a better understanding of the in vitro propagation of oil palm, giving new subsidies for future research towards a better understanding about the processes of clonal propagation of the species by somatic embryogenesis

Microstructural and electrical features of yttrium stabilised zirconia with ZnO as sintering additive

Adding ZnO reduces sintering temperature of yttria stabilized zirconia. Adding up to 0.5 wt% of ZnO is possible to densify to 8 mol% yttria stabilized zirconia (TZ8Y) to 95% of relative density at 1300 °C, besides, the electrical conductivity increases about 30% at 800 °C when compared to pure TZ8Y with the same relative density and average grain size. These results show that TZ8Y co-doped with ZnO can be a potential electrolyte to solid oxide fuel cells and electrolyzer cells.