Embora a utilização do concreto de alto desempenho (CAD) para a fabricação de elementos pré-moldados seja frequentemente usado na construção civil, o presente trabalho apresenta um estudo do emprego de microconcreto em aduelas tubulares de pequenas espessuras protendidas dentro de critérios fabris, com materiais regionais, a fim de repassar para a iniciativa privada os resultados colhidos das análises já elaboradas. As aduelas servirão para compor o tabuleiro de passarelas estaiadas, com a intenção de projetar uma estrutura que, além de harmônica aos olhos e arrojada, também seja econômica, pois se aplicando a protensão nas aduelas que formam o tabuleiro, pode-se explorar uma das características que os concretos de alto desempenho e resistência têm de melhor, que é a resistência à compressão (> 80MPa). Os materiais utilizados na dosagem do microconcreto para a confecção dos elementos em escala real, foram os seguintes: CP V ARI RS, sílica de ferro-silício em substituição volumétrica ao cimento em 10%, três tipos de areias de cava da região para o melhor empacotamento das partículas reduzindo os vazios, pedrisco basáltico com dimensão máxima de 9,5 mm em consonância com as características geométricas do elemento estrutural e da armadura e um superplastificante para atingir a consistência desejada. Levaram-se em conta na produção desse trabalho os recentes desenvolvidos havidos na reologia dos concretos frescos, ação da carbonatação e ação de cloretos. A consistência do concreto foi um fator importante para a determinação do traço, pois o concreto foi lançado nos moldes a uma altura de 2,40 m, permanecendo coeso. A concretagem foi realizada através de betonadas consecutivas para o total preenchimento do molde, onde em todas as betonadas foram realizadas a mesma seqüência de mistura pré-estabelecida. Foram moldadas duas aduelas em escala real, as quais foram estudadas seguindo a simulação do processo de montagem e uso da passarela, a fim de se analisar as solicitações atuantes e as formas de ruína das aduelas acopladas. As resistências mecânicas dos corpos-de-prova foram analisadas nas idades de 1, 3, 7, 28, 63 e 91 dias, cujos resultados de resistência à compressão simples, compressão diametral e o módulo de elasticidade atingiram ao previsto no projeto. O acabamento superficial, o tempo de lançamento, adensamento, desforma, cura e o transporte foram adequados para o reaproveitamento dos moldes. Com os resultados obtidos das análises realizadas com os dois módulos do tabuleiro, verificou-se a possibilidade de construir passarelas com elementos tubulares de pequena espessura protendidos com barras de Dywidag pelo sistema de protensão proposto. Verificou-se também uma pequena amplitude das deformações e deslocamentos das aduelas no processo de montagem e uso da passarela, assim como no transporte das aduelas. Não foram observadas a formação de quaisquer tipos de fissuras durante todo o processo envolvido, quais sejam, desmoldagem, estocagem, transporte, lançamento e utilização simulada. / Although the use of high performance concrete (HPC) for precast elements manufacture is frequently used in civil construction, this work presents a study of the utilization of microconcrete in prestressed small thicknesses tubular barrel stave, in manufacturing criteria, with regional materials, in order to repass to private initiative the already elaborated analyses results. Barrel stave will serve to compose cable-stayed footbridge deck, with the intent to project a structure that, beyond pleasant and bold, must be also economic, therefore applying prestress in barrel stave to form the deck, it\'s possible to explored the most important high performance and strength concrete characteristics, the compressive strength (> 80MPa). The used materials to design a microconcrete for the elements confection in real scale, are the following: CP V ARI RS, ferrosilicon silica fume in 10% volumetric substitution to the cement, three types of regional sands for optimum particles packing to reduce the emptinesses, 9,5 mm basaltic grave in accord with the geometric characteristics of the structural element and reinforcement, and superplasticizer additives to reach the desired consistency. Recent researches about fresh concrete rheology, carbonation and chloride action had been taken in account in the production of this work. The consistency was an important factor for concrete design, therefore the concrete would be was launched in 2,40 m height molds, remaining united. The molding was carried through consecutive load concrete mixer operation for the total fulfilling of the mold, where in all load of a concrete mixer had been carried through the same sequence of pre-established mixture. Two were molded barrel stave full scale, which were studied in the simulation of process of assembly and use of footbridge in order to examine the requests engaged in the forms of ruin from barrel stave coupled. The mechanical strength of the samples had been analyzed in ages of 1, 3, 7, 28, 63 and 91 days, whose results of simple compressive strength, diametrical compression and the modulus of elasticity had reached to the foreseen in project. The superficial finishing, the time of launching, compacting, desmoulding, cure and the transport had been adjusted for molds reuse. With the results of analyses conducted with two modules of deck, there was the possibility of building footbridges with tubular elements of small thickness prestressed with bars of Dywidag the system protention proposed. There was also a small extent of deformation and displacement of barrel stave in process of assembly and use of footbridge as well as the transport of barrel stave. Not been observed the formation of any types of cracks during all the involved process, which are, desmoulding, storage, transport, launching and simulated use.

Nas últimas décadas, houve um aumento do consumo de cerveja no Brasil e no resto do mundo. Existem diversos conceitos e metodologias que diferenciam os estilos de cerveja, sejam nas modificações dos processos de produção, uso de diferentes ingredientes, fermentações em fermentadores de diferentes tipos, metodologias de envase, utilização de madeira na maturação da bebida, entre outros. Paralelamente à evolução dos conhecimentos científicos em Microbiologia, tais como, o crescente entendimento da fisiologia celular, as técnicas de imobilização da levedura cervejeira e o isolamento de novas estirpes que fornecem características aromáticas diferenciadas às cervejas. O armazenamento de bebidas em barris de madeira é amplamente utilizado desde a antiguidade na produção de bebidas, seja na forma de armazenamento e no aumento da complexidade do produto. O objetivo desta pesquisa foi avaliar a formação de alguns compostos aromáticos durante o envelhecimento de cerveja tipo Flanders Red Ale em barris de madeira, levando em consideração aspectos químicos e microbiológicos tais como: congêneres de maturação analisando os conteúdos de compostos fenólicos de baixo peso molecular determinados por cromatografia líquida de alto desempenho, congêneres voláteis (aldeídos, ésteres e álcoois superiores) determinadas por cromatografia em fase gasosa e as propriedades microbiológicas da cerveja como viabilidade celular, meios de cultivo diferenciados para isolamento de levedura totais, bactérias ácidos acéticas, bactérias láticas e meio modificado para isolamento de Brettanomyces. O estudo foi realizado nas dependências da microcervejaria do Departamento de Agroindústria, Alimentos e Nutrição da Escola Superior de Agricultura Luiz de Queiroz, Piracicaba (SP). A fermentação primária do mosto cervejeiro foi conduzida à 23°C em fermentador cilíndrico cônico de inox, após refrigeração a 0°C por duas semanas a cerveja foi armazenada em barris (50 litros) de carvalho americano à 25°C por três e cinco meses. Após a maturação, uma cerveja nova (Young Ale) foi produzida e misturada (Blend) com a cerveja envelhecida em diferentes proporções: cerveja Young Ale; blends com 33% e 66% de cerveja envelhecida; 100% cerveja envelhecida, após os Blends, as cervejas foram engarrafadas e armazenadas por um período de três meses para início das análises químicas, microbiológicas e sensoriais. Ocorreram alterações químicas e microbiológicas que favoreceram o aumento da complexidade da cerveja após passar por um período de armazenamento em barril de carvalho, sendo que, essa alteração foi maior proporcionalmente ao aumento do tempo de armazenamento da cerveja. / In recent decades, there has been an increase in beer consumption in Brazil and around the world. There are many methodologies and concepts that differentiate styles of beer, are the modifications of the production processes, use of various ingredients fermentations in fermenters of different types of packaging methodologies, wood use in beverage maturation, among others. Parallel to the development of scientific knowledge in microbiology, such as the growing understanding of cellular physiology, the immobilization techniques of brewing yeast and isolation of new strains that provide aromatic characteristics differentiated the beers. The storage of drinks in wooden barrels is widely used since antiquity in the production of drinks. The objective of this research was to evaluate the formation of some aromatic compounds at Ale type beer aging in wooden barrels, taking into account chemical and microbiological aspects such as: maturation of similar analyzing the content of phenolic compounds of low molecular weight determined by chromatography high performance liquid volatile counterparts (aldehydes, esters and higher alcohols) determined by gas chromatography using a flame ionization detector and microbiological properties of beer analyzing cell viability, different culture media for total yeast, bacteria acetic acid, Lactic acid bacteria and growth medium modified to Brettanomyces. The study was conducted in the microbrewery premises of the agribusiness department, food and nutrition Luiz de Queiroz College of Agriculture, Piracicaba (SP). The primary fermentation was conducted at 23° C in tapered cylindrical stainless steel fermenter after cooling to 0° beer was stored in barrels (50 liters) American oak at 25° C for three and five months. After maturation, a new beer (Young Ale) was produced and blended (blend) with the aged beer bottled and stored for analysis. After maturation, a new beer (Young Ale) was produced and mixed ( Blend ) with the beer aged in different proportions : Young beer Ale ; blends of 33 % and 66 % of aged beer; 100 % aged beer, the beers were bottled and stored for a period of three months to the beginning of the chemical, microbiological and sensory analysis. Microbial and chemical chenges accurred that favored increased complexity of the beer after passing through a storage period in oak barrel, and that changes was greater in proportion to the increase beer storage time.

In this thesis is described machining of barrel steels and determination of the most suitable cutting conditions for this process. In the theoretical part was characterized cutting process and explained problems of VBD wear, chip formation and roughness of the surface. There were also explained most common cutting materials and in the last part were described CVD and PVD coating methods. In the experimental part was measured force load during turning. There was also tested eight carbide cutting inserts from SECO TOOLS. During the tests were measured additional surface roughness values and taken chip samples as well. From the evaluated load force data were determined optimized cutting conditions for machining barrel steels and most suitable type of cutting insert.

Rett syndrome (RTT), a severe neurodevelopmental disorder, affects females resulting from loss-of-function mutations in the X-linked transcription factor methyl-CpG-binding protein 2 (MECP2). RTT patients show severe verbal, motor, respiratory, and intellectual impairments. We studied two forms of activity-dependent plasticity in Mecp2 mutant mice to better understand the loss of MECP2 function in neuronal circuit and sensory processing. Sensory deprivation was applied by trimming one whisker to 3 mm to study long-term cortical plasticity in Mecp2-/y mice. Intrinsic optical signaling (IOS) imaging showed the neuronal response to wiggling a non-trimmed was consistent from day 0 to 14 but reduced for the trimmed whisker by 49.0 ± 4.3% in wild type (WT) and 22.7 ± 4.6% (p=0.0135) in RTT mice. Primary hindlimb (HL) somatosensory cortical responses to vibratory stimulation were assessed by IOS and intracortical local field potential (LFP). Responses were assessed before, during and, after 1 hour of repeated HL vibratory stimulation (100Hz,1sec, ISI 6 sec) in symptomatic male (4-6 week), female (10-12 month) and pre-symptomatic young female (4 week) RTT model mice. After 1-hour, cortical responses to test vibrations were reduced by approximately 40% in RTT and WT mice as assessed by both methods. Recovery of the IOS responses (1 sec vibration at 100Hz) and LFP (300µm below pia, 7 stimuli, 100mse ISI) were tested at 15 min intervals for 1 hour after ceasing the repeated stimulation. Reduced responses persisted for at least 60 min in WT but recovered to 90-100% of normal within 15-30 min in RTT. Analysis of the LFP responses within the test train indicated that the reduced cortical sensitivity during and after continuous stimulation resulted primarily from an increase in adaptation during the 7-stimulus test train rather than a reduction in the response to a single vibratory stimulus in all groups. Retention of this increased STA is the primary cause of the persistently reduced tactile response in young WT female mice, while in RTT mice the rapid recovery of tactile sensitivity was due to the return of STA to lower, baseline levels. Male RTT mice exhibited a marked increased excitability to the first stimulus in the test train resulting in hypersensitivity to a single vibration by 45 minutes. Old females exhibited the same pattern of adaptation and recovery but retention of adaptation was less pronounced in both WT and RTT compared to younger animals suggesting an age-dependent reduction in neural plasticity may mask deficits specific to RTT. Recording sciatic nerve sensory afferent activity did not reveal any STA, persistent adaptation or sensitization of peripheral afferent endings in any groups. I propose persistent sensory adaptation mediated by increased short-term adaptation may reflect enhanced feedback by inhibitory elements of circuits within the sensory pathway. The rapid recovery of responsiveness in young female RTT mice may therefore reflect a deficit in the capacity for activity dependent plasticity to consolidate and thus could provide a platform to understand the causes of learning and cognitive deficits in RTT patients. / Graduate

Sequence divergence of orthologous proteins enables adaptation to a plethora of environmental stresses and promotes evolution of novel functions. As one of the most common motifs in biology capable of diverse enzymatic functions, the TIM barrel represents an ideal model system for mapping the phenotypic manifestations of protein sequence. Limits on evolution imposed by constraints on sequence and structure were investigated using a model TIM barrel protein, indole-3-glycerol phosphate synthase (IGPS). Exploration of fitness landscapes of phylogenetically distant orthologs provides a strategy for elucidating the complex interrelationship in the context of a protein fold. Fitness effects of point mutations in three phylogenetically divergent IGPS proteins during adaptation to temperature stress were probed by auxotrophic complementation of yeast with prokaryotic, thermophilic IGPS. Significant correlations between the fitness landscapes of distant orthologues implicate both sequence and structure as primary forces in defining the TIM barrel fitness landscape. These results suggest that fitness landscapes of point mutants can be successfully translocated in sequence space, where knowledge of one landscape may be predictive for the landscape of another ortholog. Analysis of a surprising class of beneficial mutations in all three IGPS orthologs pointed to a long-range allosteric pathway towards the active site of the protein. Biophysical and biochemical analyses provided insights into the molecular mechanism of these beneficial fitness effects. Epistatic interactions suggest that the helical shell may be involved in the observed allostery. Taken together, knowledge of the fundamental properties of the TIM protein architecture will provide new strategies for de novo protein design of a highly targeted protein fold.

Alzheimer's Disease (AD) is a devastating neurodegenerative disease that is characterized by brain atrophy, neuronal and synaptic loss, cognitive decline, trouble handling activities of daily life, and ultimately leads to death. Worldwide, at least 30 million people suffer from AD, with 5.8 million suffering in the US alone. Despite extensive basic and clinical research, the underlying molecular mechanisms behind AD remain largely unknown. There are four FDA-approved compounds are used for alleviating symptoms but have no curative potency. The first potentially disease-modifying AD drug, aducanumb, was approved by FDA in June 2021. The main histopathological traits of AD are the Amyloid-beta (Aβ) peptide and the tau protein. Aβ aggregates to form extracellular plaques in brain parenchyma and vasculature while tau forms intraneuronal tangles. Aβ is produced by enzymatic cleavage of the amyloid precursor protein (APP) in the brain. Once APP cleavage occurs, Ab monomers either aggregate extracellularly to form buildups of sticky plaque or embed themselves within the neuronal cell membrane to form pores, causing homeostatic dysregulation and eventually cell death. The mechanism of membrane pores formed by Ab and the pore structure remain to be characterized. This study aims to analyze the structure of four Aβ species in lipid membranes. These are the most abundant form of Aβ, Aβ1-40, and the more cytotoxic form, Aβ1-42, as well as their pyroglutamylated counterparts, pEAβ3-40 and pEAβ3-42, which are hypertoxic. These peptides have been studied using biophysical approaches, i.e., circular dichroism, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. Elucidation of the structure of Aβ membrane pores provides valuable insight into the mechanism of Aβ toxicity and may help develop novel therapies for the lethal mystery that is AD.

Many plant species, including Barrel Cacti, have developed long-term evolutionary adaptable traits to survive in extreme climates. The most important trait of cacti in extreme hot dry climates is to reduce water evaporation and increase water storage. The exterior skin of a cactus plays an important role in preventing water evaporation through heat transmission. On the other hand, there have been many passive design strategies applied to the space planning and building design of architecture in hot dry climates. The goal of these passive design strategies is to regulate the penetration of heat into building spaces while creating a strong ventilation system to help bring cool air inside the building. In this paper, adaptations of the Barrel Cactus' exterior skin, along with architectural passive design strategies for hot dry climates (in this caseYazd, Iran) will be discussed and integrated with one another through the concept of Biomimicry. The goal is to design an exterior building skin that is attuned to the environmental conditions of a hot dry climate, based on the successful applicable behaviors demonstrated in the Barrel Cactus. Key architectural features such as natural ventilation and daylight will be informed by the evolutionary cacti adaptations and passive architectural strategies in the design of the building skin in order to increase the possibility of consistent comfort for users of an office building.

The role of membrane-intrinsic enzymes of lipid metabolism in complex biological processes is being realized through comprehensive structure function studies. Detailed analysis of substrate-enzyme interactions occurring within the restrictive membrane environment has proved to be exceedingly challenging. Using detergent micelles, we describe a detailed model for substrate recognition and binding by the outer-membrane intrinsic enzyme PagP from Escherichia coli. PagP is an 8-stranded antiparallel β-barrel that transfers a palmitoyl group from a phospholipid molecule to lipid A, the endotoxin component of lipopolysaccharide. This simple modification provides bacterial resistance to host antimicrobial peptides and attenuates the inflammatory response signalled through the host toll-like receptor 4 pathway. We describe a molecular embrasure and a crenel, which display weakened transmembrane β-strand hydrogen bonding, to provide site-specific routes for lateral entry of substrates into the PagP active site. A Tyr147 localized to the L4 loop gates the entry of the phospholipid substrate through the crenel, while lipid A enters via the embrasure. The side chains of the catalytic residues that are located in the extracellular loops point towards the central axis of the enzyme, directly above the active site. An acyl-chain binding pocket known as the hydrocarbon ruler is buried within the transmembrane β-barrel structure, and is optimized to accommodate a 16-carbon saturated palmitate chain. The hydrocarbon ruler, therefore, accounts for PagP's stringent selectivity for a palmitate chain. Substituting Gly88 lining the floor of the hydrocarbon ruler with residues possessing linear, unbranched, aliphatic side chains changes the selectivity of PagP to utilize shorter acyl chains. The serendipitous discovery of an exciton interaction between Trp66 and Tyr26 at the floor of the hydrocarbon ruler provides an intrinsic spectroscopic probe to monitor the methylene unit acyl-chain resolution of PagP. A compromised acyl chain resolution of the Gly88Cys mutant is attributed to an unexpected decrease of the Cys sulfhydryl group pKa within the β-barrel interior, resulting in a burying of a charged thiolate within the PagP core. The structural perturbation associated with the Cys thiolate extinguishes the exciton and expands the acyl-chain selectivity. These molecular details of lateral lipid diffusion and acyl-chain selection provide the first such example for any membrane-intrinsic enzyme of lipid metabolism. / Thesis / Doctor of Philosophy (PhD)

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