O comportamento reológico de suspensões concentradas heterogêneas como concretos e argamassas possui influência direta na energia requerida e na produtividade durante o processamento e aplicação destes materiais, além de ser um fator determinante na obtenção de um produto final qualidade. De um modo geral pode-se dizer que a fluidez destas suspensões está diretamente relacionada à facilidade de movimentação das partículas, logo pode-se inferir que a redução dos fenômenos atrito é um fator determinante para o bom desempenho destas suspensões durante o fluxo. Deste modo, este trabalho buscou por meio de modelos ideais de esferas e silicone líquido avaliar a influência do coeficiente de atrito dos agregados e da viscosidade da matriz no comportamento reológico de suspensões concentradas. O coeficiente de atrito de agregados esféricos com diferentes granulometrias foi determinado experimentalmente através do ensaio de cisalhamento direto, também conhecido como shear box, e o comportamento reológico de suspensões compostas por estes agregados e silicones líquidos de diferentes viscosidades foram avaliadas por meio do ensaio de squeeze flow. Os resultados revelam que a distribuição granulométrica possui um influência no coeficiente de atrito dos agregados e que esta propriedades está relacionada a área e ao tipo de contato entre as partículas. Entretanto, para o tipo de fluxo e para as velocidades as suspensões, não houve uma relação direta entre o coeficiente dos agregados e a viscosidade da suspensão. Além disto, apesar de alterar o comportamento reológico das suspensões a viscosidade da matriz não apresentou uma relação direta com viscosidade da suspensão, o que em partes ser explicados pela provável ocorrência de um fluxo não homogêneo das suspensões nas condições aqui estudadas. / The rheological behavior of concentrated suspensions like concrete and mortars plays an important hole during their processing and application, and also has a great influence on the final product quality. The flowability of these suspensions is directly related to the ease of particle motion in the system, therefore reduction of friction phenomena contributes for a good flow behavior. The aim of this work was to determine the influences of aggregates friction coefficient and the liquid viscosity of the fluid matrix on the rheological behavior of concentrated suspensions. The friction coefficient of glass spheres with different particle size distributions were determined by shear box tests, while the rheological behavior of concentrated suspensions composed by these glass spheres and silicone oils was evaluated by squeeze flow tests. Results revealed that the particle size distribution influences the coefficient of friction, and this property is determined by the type and the area of contact between the particles. However, for the kind of flow and the speed used in the experiments, there was no relation between friction coefficient and the suspension viscosity. Additionally, matrix viscosity has an impact on the rheological behavior of the system, but no clear relation was identified, which may be caused by the occurrence of heterogeneous flow under the applied experimental conditions.

Submitted by Caroline Falcao (caroline.rfalcao@ufpe.br) on 2017-06-06T17:10:34Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) 2012-Dissertacao-GustavoAlexandreSilva.pdf: 10928701 bytes, checksum: 44c2b4f22827eed6eae53c17ea822ea3 (MD5) / Made available in DSpace on 2017-06-06T17:10:35Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) 2012-Dissertacao-GustavoAlexandreSilva.pdf: 10928701 bytes, checksum: 44c2b4f22827eed6eae53c17ea822ea3 (MD5) Previous issue date: 2012 / O setor de agregados para a construção civil possui a parcela de insumos minerais mais consumidos e, consequentemente, os mais significativos em termos de quantidades produzidas no mundo. Apesar de serem abundantes e apresentarem baixo valor unitário, seu consumo é um importante indicador do perfil sócio-econômico de desenvolvimento de um país, estado ou região metropolitana. Este trabalho foi concebido no intuito de suprir a carência de informações e dados sobre o setor de agregados para construção civil na Região Metropolitana de Natal-RN (RMN), conforme sua geologia e os recursos minerais, modo de ocorrência, especificações dos materiais e dados econômicos. Formada por dez municípios, a RMN se apresenta como uma das regiões de maior dinamismo econômico-social do Estado. Em relação a sua urbanização, a diferença é visivel, uma vez que a população rural supera a população urbana em alguns municípios. Sua área abrange uma superfície de 2.807,54 km², isto corresponde a 5,3% do território estadual. Sua população, de acordo com o Censo Demográfico de 2010, atingiu 1.351.004 habitantes. Isso representa 42,6% da população do Rio Grande do Norte (3.168.133 habitantes), compreendendo uma taxa de crescimento no período 2000 – 2010 de 1,88% ao ano. O Produto Interno Bruto (PIB) da RMN teve um aumento consistente de 2003-2008. No entanto, sua constribuição para o PIB do Estado, cai em média 0,63% ao ano devido processo de interiorização do desenvolvimento que o Rio Grande do Norte vem passando nos últimos anos. Na abordagem da geologia optou-se pela discussão dos registros geológicos em termos de unidades pré-quaternárias (anteriores a 2 milhões de anos) e unidades quaternárias. As rochas britadas e os sedimentos como areias e cascalhos são os materiais naturais utilizados como agregados na construção civil. Enquanto os sedimentos são usados, geralmente, como encontrados na natureza, as rochas podem passar por processos de britagem e moagem para atingir as especificações granulométricas. Na data da consulta havia registrados no DNPM destinados a produção de areia e brita 57 processos e dentre os 10 municípios da RMN os que apresentaram maiores quantidades de processos minerários foram: São Gonçalo do Amarante (28%), Ceará - Mirim (19%) e Monte Alegre (19%). O método de lavra de areia comumente utilizado na RMN é o de dragagem em leito de rio ou cava submersa, já que cerca de 85% da produção são proveninetes de áreas localizadas nos leitos dos rios. Os 15% restantes vêm dos terraços denominados de depósitos eólicos, riachos de menor porte. No caso da explotação de Brita o método de lavra é a céu aberto. O consumo de brita da Grande Natal é suprido pela produção de unidades pertencentes a três grupos empresariais. A produção de brita para a Grande Natal, foi estimada em 1.570.140 m3 /ano ou 2.590.731 t/ano, enquanto que a ociosidade média das instalações de beneficiamento das unidades produtoras está próxima de 50%. Em 2011 a produção anual de areia para construção civil foi de 1.967.159 m³ ou 2.950.738 t. Os Preços médios de brita, pesquisados, variaram desde R$ 30,00/t (ROM) até R$ 58,00/t (nas casas de materiais de construção), já os de areia foi de R$ 7,00 /t (ROM) até R$ 20,00/t (no varejo). As reservas estimadas (medidas e indicadas) de agregados, considerando a produção consumida atualmente na RMN, são suficientes para atender a demanda projetada para os proximos 15 anos isto sem levar em conta as reservas inferidas que podem aumentar substancialmente este tempo. / The most widely used inputs in the construction aggregates sector in the world are the mineral. Despite their abundance and low unit value, their use is an important indicator of the socioeconomic profile of a country, state or metropolitan region. This paper aimed to provide information and data, which are scarce, on the construction aggregates segment in the Metropolitan Region of Natal – RN (RMN), considering its geology, mineral resources, mode of occurrence, material specifications and economic data. Formed by ten cities, the RMN is the State region with the greatest economic and social dynamics. Regarding its urbanization, the rural population exceeds the urban population in some cities. The RMN covers an area of 2.807,54 km², accounting for 5.3% of the state territory. According to Brazilian Census 2010, its population reached 1,351,004 inhabitants, which corresponds to 42.6% of the population of Rio Grande do Norte (3,168,133 inhabitants), and a growth rate in the 2000 – 2010 period of 1.88% per year. The Gross Domestic Product (GDP) of the RMN has increased consistently from 2003-2008. However, its contribution to the state GDP falls 0.63% on average per year due to the recent process of internal development in Rio Grande do Norte. Concerning the geological approach, we decided to focus on the pre-quaternary (< 2 million years ago) and quaternary geologic periods. The crushed rocks and sediments such as sand and gravel are natural materials used as aggregates in construction. As the sediments are used generally in their natural condition, the rocks may undergo crushing and grinding process to achieve the required specifications. On the date of the consultation there were 57 processes recorded at the DNPM for the production of sand and gravel. São Gonçalo do Amarante (28%), Ceará - Mirim (19%) and Monte Alegre (19%) were the RMN cities with the highest number of mineral processing activities. The sand mining method commonly used in the RMN concerns river bed dredging or digging trial pits, since 85% of the production comes from fields located in riverbeds. The remaining 15% come from terraces known as aeolian deposits, small streams. Regarding the exploitation of gravel, the open pit mining method is used. The consumption of gravel in the Grande Natal region is supplied by production units belonging to three business groups. The production of gravel in the Grande Natal region was estimated in 1,570,140 m3 /year or 2,590,731 t/year, while the average idleness of the processing facilities of the production units close to 50%. In 2011 the annual building and construction sand was 1,967,159 m³ or 2,950,738 t. The average prices of gravel found ranged from R$ 30,00/t (ROM) to R$ 58,00/t (in construction material shops). The average prices of sand, in turn, ranged from R$ 7,00 /t (ROM) to R$ 20,00/t (in retail stores). Given the current production rates of aggregates in the RMN, the estimated reserves (measured and indicated) are sufficient to meet the demand forecast for the next 15 years, without taking into consideration the inferred reserves that can substantially increase this period.

Tauopathies are neurodegenerative diseases that affect millions of people around the world. Tauopathies include more than 20 neurodegenerative diseases. Some of the most common tauopathies are Alzheimer’s disease (AD), frontotemporal dementia (FTD), chronic traumatic encephalopathy (CTE), Pick’s disease, corticobasal degeneration, progressive supranuclear palsy (PSP), agyrophillic grain disease, and amyotrophic lateral sclerosis (ALS). These diseases can cause significant memory loss, behavioral changes, motor deficits and speech impairments. Tauopathies stem from accumulation of the microtubule associated protein tau (MAPT). Tau stabilizes microtubules and helps with axonal transport. In a disease state tau becomes hyperphosphorylated and truncated leading to its aggregation. More recently tau has been shown to propagate from cell to cell potentially acting as a signaling molecule that contributes to disease progression. In addition during disease, tau mislocalizes to dendrites leading to synaptic dysfunction. This mislocalization may also lead to subsequent neurodegeneration. Today, many strategies have been implemented to treat tauopathies. Some of these strategies include kinase inhibitors, immunotherapy, tau aggregation inhibitors, and microtubule-stabilizing compounds. However none these strategies have been effective in stopping tau pathology nor do they address tau degradation pathways. Therefore we hypothesized that utilizing small molecules that target degradation pathways such as autophagy or proteasomal degradation would improve clearance of aberrant tau. We previously showed that a natural product (+)-aR,11S-myricanol (1) from Myrica cerifica (bayberry/southern wax myrtle) root bark reduced levels of tau. In this study we discovered that 1 is composed of two enantiomers and two possible atropisomers. We found that one enantiomer (-)-aS,11R-myricanol (3) was responsible for the anti-tau activity of 1 in multiple models of tauopathy. We also found that 3 selectively targets and lowers specific tau species. To better understand how these tau species were being reduced we took a non-biased approach and subjected 3 treated samples to stable isotope labeling by amino acids in cell culture (SILAC) mass spectrometry (MS) proteomic analysis. We found that autophagy pathways were most affected by 3 and that 3 was predicted to mimic the drug rapamycin, a well-established macroautophagy activator. In addition we confirmed our MS findings by simultaneously giving 3 treated cells an autophagy inhibitor which blocked 3’s tau reductions. Moreover we created a tetralin derivative of 1, 13, that produced the same effects on tau as 3 but did not rely upon stereochemistry for its activity. This work supports targeting the autophagy degradation pathway as a viable approach to improving aberrant tau accumulation. In order to further support our hypothesis, we collected and screened several known heat shock protein 70 (Hsp70) inhibitors and tau aggregation inhibitors for cellular anti-tau activity. While it is known that Hsp70 inhibition facilitates tau clearance through proteasomal degradation, it is not known what role tau aggregation inhibition plays in the cellular degradation of tau. Moreover understanding which inhibitory activity contributes most to tau degradation would lead to the creation of better drug scaffolds. In this study, we found that several Hsp70 inhibitors from different scaffold backbones had varying effects on tau degradation. The rhodacyanine and phenothiazine compounds were most effective at lowering cellular tau while the adenosine analog, sulfonamide, dihyropyrimidine, piperidine-3-carboxamide, phenoxy-N-arylacetamide, and flavonol, were not as effective. We also examined the effects of several tau aggregation inhibitor scaffolds such as the carbocyanine, oleuropein, anthraquinone, aminothienopyridazine, hydroxytyrosol and rhodanine on tau expression reduction. We found that none had effective tau reductions except the carbocyanine. However when we performed a lactate dehydrogenase (LDH) assay, carbocyanine was shown to be extremely toxic. These results lead us to further investigate if the tau expression reducing Hsp70 inhibitors had anti-tau aggregation activity and if the tau aggregation inhibitors had any Hsp70 inhibitory activity. We discovered that many of the Hsp70 inhibitors also had anti-tau aggregation activity while none of the aggregation inhibitors had Hsp70 inhibitory activity. We found a positive correlation between tau expression reductions and anti-tau aggregation activity for the Hsp70 inhibitors. Our work demonstrates that both Hsp70 activity and tau aggregation in vitro best predicts anti-tau activity of small molecules. Also these dual acting Hsp70 inhibitors support our hypothesis that targeting the degradation pathways can improve tau clearance. Overall, this work indicates the importance of targeting degradation pathways to improve tau clearance. Utilizing small molecules that have dual activities against tau could prove beneficial as a novel therapeutic approach to treat tauopathies. In addition using small molecules that target different degradation pathways simultaneously could be another viable therapeutic strategy for treatment of tauopathies.

This thesis examines the effect of population ageing on macroeconomic aggregates. The author´s objective is to verify, whether there exists any relationship of the population ageing factors and the GDP growth rate, social expenditures growth rate and the consumption growth rate. Econometric models are based on theoretical specifications of Faruqee´s life-cycle model and Prettner´s R&D model with overlapping generations. The degree of economic development is also taken into account. Furthermore, the author modified the R&D model by incorporation of the poverty indicator and its application on available datasets. The research is focused on five European countries in 1995 - 2013. The Ordinary Least Squares method is used to gain estimated results in regression analyses. The author managed to prove an existing relationship between the old age dependency ratio and the social expenditures in all countries except Switzerland. The impact of the population ageing factor on the consumption growth rate turned out to be significant in all of those countries. Substantial fluctuations are shown only in Bulgaria and in the Czech Republic. The GDP growth rate seems to be influenced by ageing factor in the Czech Republic and in the Ukraine alone. The research has also shown that developing countries respond more dramatically to changes in the population structure distribution, while the poverty indicator plays an important role only in the Ukraine.

This paper presents results on experimental research for concrete produced using recycled coarse aggregates (RCA). Five types of coarse aggregates were used in this study, four of which were RCA. The main purpose of this research was to examine how different types and properties of coarse aggregate affected compressive strength, modulus of elasticity, and shrinkage in concrete when natural coarse aggregates were replaced with RCA. Concrete batches were made with water-cement (w/c) ratios of 0.30, 0.45, and 0.60, and substitution percentages ranged from 0% to 100% of natural aggregate with RCA. Test results clearly show that compressive strength, modulus of elasticity, and shrinkage greatly depend on the quality and type of coarse aggregate used. In addition to testing of hardened concrete, predictive models for elasticity and ultimate shrinkage were developed to formulate and reinforce proposed conclusions about the properties and performance for the different RCA.

No description available.

A theoretical model describing photophysics of π-conjugated aggregates, such as molecular crystals and polymer thin films, is developed. A Holstein-like Hamiltonian expressed with a multi-particle basis set is used to evaluate absorption and photoluminescence (PL) spectra of neutral excitons as well as charge modulation spectra (CMS) and transient absorption spectra (TAS) of positively charges hole-type polarons. The results are used to develop a better theoretical understanding of the organic electronics being studied and their photophysics, and also to probe the morphology of poly(3-hexylthiophene) (P3HT) thin films, which are used in photovoltaic devices. / Chemistry

<p> Tissue plasminogen activator (tPA), is commonly used as thrombolytic agent for the treatment of various cardiovascular diseases. This thesis constitutes the first report on cloning and expression of tPA in the methylotrphic yeast Pichia pastoris. </p> <p> The tPA gene was first cloned into an E. coli/Pichia shuttle plasmid and then integrated into the Pichia genome. The recombinant Pichia was able to express tPA intracellularly, under methanol induction. The tPA produced by the Pichia had a similar molecular weight as native tPA and it had serine protease activity. At the shake flask scale, the recombinant Pichia strain was able to produce twice as much tPA as reported for E. coli. </p> <p> Elastin-like polypeptides (ELP) are proteins that have a peculiar characteristic: they are able to undergo a reversible inverse phase transition temperature within a very narrow temperature range. On a second aspect of heterologous protein, a construct composed of thioredoxin-intein-ELP was used to provide direct evidence, for the first time, that protein folding and activity, in this case the intein, was maintained when the tripartite fusion was present in the aggregated state. These results are important, since they provide the necessary degree of confidence to stimulate future work directed towards expression and maintenance of proper folding of aggregation-prone proteins when expressed in-vivo E. Coli as ELP directed inclusion bodies. It is also shown that the intein-ELP system may be a very interesting system to be used as a drug delivery vehicle. </p> / Thesis / Master of Applied Science (MASc)

A wide variety of adherent mammalian cells can be induced into a reversible state of metabolic arrest (quiescence) by conversion to non-adherent multicellular aggregates. These "spheroids" can be maintained at room temperature under oxygen- and nutrient-deprived conditions for extended periods of time (weeks) as well as converted back to viable proliferating monolayers. Herein it is shown that HEK293 spheroid arrest and recovery requires the co-activation of both NF-kB and JNK, and chemical inhibition of either NF-κB nuclear translocation or JNK phosphorylation leads to cell death. Cytokine profiling within the aggregates during the arrest and recovery process is suggestive that a cyclical cascade was in operation, leading to endogenous cytokine production of TNF-Alpha, IL-1Beta, and IL-8, thereby propagating the cellular stress signal within cells as well as throughout the aggregate. Cytokines exist <i>in vivo</i> as mixtures, yet tissue culture studies delineating how cells respond to these molecules are often performed using individual effectors added exogenously. Are the results obtained in these studies true representations of physiological responses? As HEK293 multicellular aggregates (spheroids) survive long term arrest by endogenous cytokine (TNF-α and IL-1β) and chemokine (IL-8) signaling, adherent monolayer cells were evaluated for their ability to provide a "spheroid signal response" when exposed to TNF-α, IL-1β and IL-8 individually, and in combination, at concentrations observed in the aggregates. The spheroid signal transduction response was only observed when all three cytokines were present, demonstrating that signal transduction cascade mechanisms are cytokine-profile dependent. To determine if similar processes were involved in the arrest and recovery of multicellular aggregates derived from other cell types, the responses of primary human foreskin fibroblasts (HFF-2) and a glioblastoma cell line (T98G) were characterized, utilizing the procedures developed in the HEK293 study. Both the T98G and HFF-2 cell lines entered and exited from the long term arrest utilizing an autocrine response. However, while the carcinoma cell line was dependent upon NF-κB for survival, its signaling partner was Gadd45α and signaling occurred through the p38 pathway. Primary fibroblast arrest and recovery proceeded through the p38 pathway as well, but was independent of NF-κB. Thus, three different cell types and transformation states (HEK293, HFF-2, and T98G) provided three different routes to survival, all with cyclical cytokine production and signaling. These routes cannot be measured or modulated effectively in adherent monolayers. Multicellular aggregates provide higher ordered systems that can be used to describe signaling pathways within a cell, highlighting the role of autocrine responses and the synergistic relationships between cytokines and neighboring cells. / Ph. D.

The effects of maximum size coarse aggregate on the relationship between accelerated strength and 14-day normally cured strength of normal and superplasticized concrete have been investigated. The results obtained show that differences among maximum size coarse aggregates are greater in normal concrete than in superplasticized concrete in strength-producing properties. Among the various sizes of aggregates investigated, one-half inch maximum size of coarse aggregate exhibited higher strength producing properties. This report includes the test results as well as the procedures for the preparation and testing of concrete specimens. These specimens were prepared and tested at the concrete laboratory at Virginia Polytechnic Institute and State University. / Master of Science / incomplete_metadata