The development of effective methods to cryopreserve precious cell types has had tremendous impact on regenerative and transfusion medicine. Hematopoietic stem cell (HSC) transplants from cryopreserved umbilical cord blood (UCB) have been used for regenerative medicine therapies to treat conditions including hematological cancers and immodeficiencies. Red blood cell (RBC) cryopreservation in blood banks extends RBC storage time from 42 days (for hypothermic storage) to 10 years and can overcome shortages in blood supplies from the high demand of RBC transfusions. Currently, the most commonly utilized cryoprotectants are 10% dimethyl sulfoxide (DMSO) for UCB and 40% glycerol for RBCs. DMSO is significantly toxic both to cells and patients upon its infusion. Glycerol must be removed to <1% post-thaw using complicated, time consuming and expensive deglycerolization procedures prior to transfusion to prevent intravascular hemolysis. Thus, there is an urgent need for improvements in cryopreservation processes to reduce/eliminate the use of DMSO and glycerol. Ice recrystallization during cryopreservation is a significant contributor to cellular injury and reduced cell viability. Compounds capable of inhibiting this process are thus highly desirable as novel cryoprotectants to mitigate this damage. The first compounds discovered that were ice recrystallization inhibitors were the biological antifreezes (BAs), consisting of antifreeze proteins and glycoproteins (AFPs and AFGPs). As such, BAs have been explored as potential cryoprotectants, however this has been met with limited success. The thermal hysteresis (TH)activity and ice binding capabilities associated with these compounds can facilitate cellular damage, especially at the temperatures associated with cryopreservation. Consequently, compounds that possess “custom-tailored” antifreeze activity, meaning they exhibit the potent ice recrystallization inhibition (IRI) activity without the ability to bind to ice or exhibit TH activity,are highly desirable for potential use in cryopreservation. This thesis focuses on the rational design of potent ice recrystallization inhibitors and on elucidating important key structural motifs that are essential for potent IRI activity. While particular emphasis in on the development of small molecule IRIs, exploration into structural features that influence the IRI of natural and synthetic BAs and BA analogues is also described as these are some of the most potent inhibitors known to date. Furthermore, this thesis also investigates the use of small molecule IRIs for the cryopreservation of various different cell types to ascertain their potential as novel cryoprotectants to improve upon current cryopreservation protocols, in particular those used for the long-term storage of blood and blood products. Through structure-function studies the influence of (glyco)peptide length, glycosylation and solution structure for the IRI activity of synthetic AFGPs and their analogues is described. This thesis also explores the relationship between IRI, TH and cryopreservation ability of natural AFGPs, AFPs and mutants of AFPs. While these results further demonstrated that BAs are ineffective as cryoprotectants, it revealed the potential influence of ice crystal shape and growth progression on cell survival during cryopreservation. One of the most significant results of this thesis is the discovery of alkyl- and phenolicglycosides as the first small molecule ice recrystallization inhibitors. Prior to this discovery, all reported small molecules exhibited only a weak to moderate ability to inhibit ice recrystallization. To understand how these novel small molecules inhibit this process, structure-function studies were conducted on highly IRI active molecules. These results indicated that key structural features, including the configuration of carbons bearing hydroxyl groups and the configuration of the anomeric center bearing the aglycone, are crucial for potent activity. Furthermore, studies on the phenolic-glycosides determined that the presence of specific substituents and their position on the aryl ring could result in potent activity. Moreover, these studies underscored the sensitivity of IRI activity to structural modifications as simply altering a single atom or functional group on this substituent could be detrimental for activity. Finally, various IRI active small molecules were explored for their cryopreservation potential with different cell types including a human liver cell line (HepG2), HSCs obtained from human UCB, and RBCs obtained from human peripheral blood. A number of phenolic-glycosides were found to be effective cryo-additives for RBC freezing with significantly reduced glycerol concentrations (less than 15%). This is highly significant as it could drastically decrease the deglycerolization processing times that are required when RBCs are cryopreserved with 40% glycerol. Furthermore, it demonstrates the potential for IRI active small molecules as novel cryoprotectants that can improve upon current cryopreservation protocols that are limited in terms of the commonly used cryoprotectants, DMSO and glycerol.

One of the largest problems in current medicine is the shortage of organs for transplant due to technological limitations in the storage of organs for any length of time. A possible solution to this problem would involve cryopreservation. However, current cryopreservatives such as sucrose or DMSO have concerning cytotoxic issues that limit their possible applications. A major cause of cryoinjury is the uncontrolled recrystallization of inter and intra-cellular ice crystals that occurs during the thawing process leading to mechanical damage and dehydration. The Ben lab has thus been interested in the design of compounds that are capable of inhibiting this process but do not possess other undesirable properties found in the native compounds. These synthetic analogues have been shown to increase cellular viability post-thaw. A series of mixed α/β glycopeptides are prepared and analyzed for antifreeze properties. The results of this study imply that it is not the gross conformation of the glycopeptide that is responsible for activity, but rather that intramolecular relationships may be responsible for disrupting the reorganization of ice. A technique was devised for the incorporation of triazoles into the analogues to investigate the importance of the linker and to greatly simplify the synthesis of a library of glycoconjugates. It was found that the IRI activity of glycopeptides is very sensitive to the distance between carbohydrate and peptide backbone. The electron density at the anomeric oxygen is an important parameter with respect to intramolecular networks. A series of substituted galactosides is presented that modify the electronics of the anomeric oxygen. The results demonstrate that decreasing electron density at this position appears to improve IRI activity in a predictable manner. To better understand the remarkable IRI activity of a key analogue, it was systematically truncated. This study led to the serendipitous discovery of a series of very highly IRI active analogues that do not contain a peptide backbone. These compounds represent the first non-glycopeptides that can show very significant IRI activity even at very low concentrations. The final portion of the thesis reports the efforts towards the preparation of a carbasugar analogue of AFGP-8.

No description available.

The effect of initial microstructures of an 0.05 wt.% C low carbon steel, acicular ferrite (AF), Bainite (B), polygonal ferrite (PF), fine polygonal ferrite (FPF), and a microstructure produced by direct strip casting (DSC) (termed SC), on the deformation and recrystallization behaviour of cold rolled low carbon (LC) steel, was investigated. The initially prepared samples with the initial microstructures were cold rolled to 50, 70 and 90% reductions, then annealed isothermally in the temperature range 580 ??? 680 oC. The microstructures and textures produced by deformation and annealing were studied by optical microscopy, XRD, TEM, SEM and EBSD. The initial microstructures were characterized mainly by optical microscopy and EBSD. Using EBSD, the ferrite grain size of the AF, B and SC samples was considerably larger than that found by optical microscopy with a large fraction of low angle grain boundaries (LAGBs) observed within prior austenite grains. All samples exhibited a very weak texture close to random. After cold rolling, the microstructures of AF and SC contained shear bands with PF and FPF generating deformation bands. For AF and SC, the pearlite phase was more extensively elongated in rolling direction compared with PF and FPF. After 90% cold rolling reduction, PF, FPF and SC consist mainly of the texture component and AF and B . It was found that FPF recrystallized most rapidly followed by B, PF and AF with SC recrystallizing orders of magnitude more slowly due to the solution drag caused by its uniformly distributed higher Mn content. Very strong (???-fibre) texture was generated in cold rolled PF followed by FPF, with AF, SC and B generating very weak textures. The texture evolution during annealing 90% reduction PF was examined in further detail. The behaviour of nucleation and grain growth provides strong evidence of orientated nucleation as the dominant factor for CRA texture development in this material.

Made available in DSpace on 2014-10-09T12:52:01Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:53Z (GMT). No. of bitstreams: 0 / Tese (Doutoramento) / IPEN/T / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP

Three aluminium alloys from AA3003 series modified by zirconium were pre- pared by twin-roll casting. The role of composition, heat treatment and deforma- tion by cold-rolling or equal channel angular pressing on evolution of microstruc- ture and mechanical properties were studied. High density of α-Al(Mn,Fe)Si pre- cipitates formed during annealing between 300 ◦ C and 500 ◦ C. Coherent Al3Zr particles precipitated during annealing at 450 ◦ C with slow heating rate. Recrys- tallization resistance of deformed alloys was enhanced by either Al3Zr precipitates formed before deformation or by α-Al(Mn,Fe)Si particles nucleating simultane- ously with recrystallization. 1

A fusão zonal compreende uma família de métodos para controle e distribuição de impurezas na qual uma pequena zona fundida é deslocada lentamente ao longo de um material sólido, redistribuindo o soluto. Ela é utilizada na purificação de materiais, num processo denominado refino zonal, mas também pode ser usada na distribuição homogênea ou descontínua de impurezas e no crescimento de cristais. A fusão zonal aplicada ao crescimento de grãos, visando a obtenção de materiais mono ou policristalinos com grãos grosseiros é denominada recristalização por fusão zonal (ZMR) e seu uso principal é na preparação de materiais para fabricação de dispositivos eletrônicos e fotovoltaicos, especialmente em silício. Na última década, o progresso na tecnologia ZMR foi feito principalmente em três campos: desenvolvimento de equipamento, controle de processo e modelagem numérica, mas somente algumas pesquisas abordam a fusão zonal a baixas temperaturas e restringem a aplicação do método a outros materiais semicondutores como os elementos do grupo III, IV ou V. Deste modo, o presente trabalho tem como objetivo verificar a influência da velocidade de varredura, da largura da zona fundida e do número de passadas no processo de fusão zonal de materiais de baixo ponto de fusão, em relação à obtenção de materiais policristalinos com grãos grosseiros. Para tanto, construiu-se um equipamento de fusão zonal horizontal e barras de alumínio puro (P0610) foram submetidas ao processo, variando os parâmetros acima referidos. A macroestrutura das amostras foi analisada e os resultados obtidos do número de grãos/área foram interpretados, verificando a influência dos parâmetros físicos anteriormente citados, do gradiente térmico e do super-resfriamento constitucional. Verificou-se que a redução na velocidade de varredura e na largura da zona fundida, de modo geral, mostrou-se eficiente em relação à diminuição do número de grãos por área. Os resultados obtidos indicam que a fusão zonal foi efetiva na obtenção de alumínio policristalino com grãos grosseiros e colaboram para melhorar a compreensão do processo. / The zone melting comprises a family of methods to control and to distribute impurities in which a small molten zone is moved slowly along a solid material, redistributing solute. It is used in materials purification, in a so-called zone refining process, but can also be used in homogeneous or discontinuous distribution of impurities and crystal growth. The zone melting applied to grain enlargement, leading to attain singlecrystalline or polycrystalline materials with coarse grains is so-called zone melting recrystallization (ZMR) and its major use is the preparation of materials for electronic and photovoltaic devices process especially silicon. In the last decade, progress in ZMR technology was done mainly in three areas: equipment development, process control, and numerical modeling, but only a few researches handle on zone melting at low temperatures and it limits the application of the method to other semiconductor materials such as III, IV or V group elements. Thus, this study aims to examine the influence of scan rate, zone width and the number of zone passes in the zone melting process of low melting point materials about getting polycrystalline materials with coarse grains. For this, horizontal zone melting equipment was built and pure aluminum bars (P0610) were zone melted, varying the parameters mentioned above. The macrostructure of the samples was analyzed and the results of the number of grains per area were assessed by checking the influence of physical parameters previously mentioned and the thermal gradient and the constitutional supercooling. It was found that scan rate and zone width reduction in general, proved to be efficient in reducing the number of grains per area. The results indicate that the zone melting was effective in obtaining aluminum polycrystalline coarse-grained and collaborate to improve the understanding of the process.

Submitted by Celso Bortolini Júnior null (celsobortjr@gmail.com) on 2016-03-14T21:15:08Z No. of bitstreams: 1 Dissertação Celso Bortolini Junior.pdf: 5854950 bytes, checksum: e97a433411ce86089561ffba7119ff02 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-15T13:34:55Z (GMT) No. of bitstreams: 1 bortolinijunior_c_me_guara.pdf: 5854950 bytes, checksum: e97a433411ce86089561ffba7119ff02 (MD5) / Made available in DSpace on 2016-03-15T13:34:55Z (GMT). No. of bitstreams: 1 bortolinijunior_c_me_guara.pdf: 5854950 bytes, checksum: e97a433411ce86089561ffba7119ff02 (MD5) Previous issue date: 2016-01-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Titânio e suas ligas são utilizados em implantes biomédicos devido a suas excelentes propriedades de volume, como resistência mecânica. Porém, tais propriedades estão diretamente ligadas à microestrutura, que por sua vez depende do processamento. O objetivo deste trabalho foi avaliar a microestrutura e a evolução da recristalização da liga Ti30Ta deformada a frio, após tratamento térmico. Os lingotes da liga Ti30Ta foram obtidos em um forno de fusão a arco voltaico. A liga foi tratada em um forno tubular sob vácuo a 950ºC por 24 horas para garantir a homogeneidade química e então foi forjada a frio em barras de 10 mm de diâmetro. As amostras foram solubilizadas a 900ºC por 2 horas e temperadas em água. Discos de 3 mm de espessura foram usados para análise. Para a avaliação da recristalização, foi realizado um tratamento térmico a 750ºC, 800ºC e 850ºC por 12 horas seguido de têmpera em água. A morfologia, composição e estrutura foram investigadas usando microscopia óptica, microscopia eletrônica de varredura, microscopia eletrônica de transmissão e difração de raios X. As análises de microscopia e difração de raios X indicaram a presença apenas da fase martensítica α'' na amostra solubilizada e a presença das fases α'' e α' nas amostras recristalizadas. Os ensaios mecânicos mostraram que houve uma melhoria nas propriedades mecânicas após a recristalização, sendo a temperatura de 750° que teve maior influência, porém houve também um incremento no módulo de elasticidade, o que é indesejado. / Titanium and its alloys have been used in biomedical devices due their excellent bulk properties, such as mechanical strength. However, these properties are very sensitive of microstructures which depend of the processing. The purpose of this study was to evaluate the microstructure and evolution of recrystallization of the could-swaged Ti30Ta alloy after heat treatment. Ingots of Ti30Ta alloy were obtained in arc melting furnace. Alloys were treated at 950° C for 24 hours for chemical homogenization in vacuum tubular furnace and cold worked by swaging into rods with 10 mm in diameter. Samples where then solution treated at 900° C for 2 hours and water quenched. Discs with 10 mm in diameter and 3 mm in thickness were used for analysis. For recrystallization evaluation, heat treatment was carried out at 750º C, 800º C and 850º C for 12 hours followed by water quenching. The morphology, composition and structure were investigated using optical microscopy, scanning electron microscopy, transmission electron microscopy and XRD (X-rays Diffraction Analysis). The microscopy and XRD analysis indicate the presence of the martensitic phase α'' for the solution treated sample and the presence of both α'' and α' phases for the recrystallized samples. Mechanical tests shows an increase in the mechanical strength to all the samples after recrystallization, with the temperature of 750° being the most impacting, however, it led an unwanted increase to the elastic modulus.

Made available in DSpace on 2014-06-11T19:32:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-01-30Bitstream added on 2014-06-13T20:43:24Z : No. of bitstreams: 1 oliveirajr_vt_dr_rcla.pdf: 9760804 bytes, checksum: d9da7a283e80e74c48d4bab2dced138d (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A grande variedade de microestruturas e texturas encontradas nos minérios de ferro do Quadrilátero Ferrífero no Brasil gera uma ampla diversidade de propriedades físicas com grandes implicações para o seu beneficiamento. O vínculo entre reologia, mecanismos de deformação que atuaram na formação de várias microestruturas e texturas ou orientações cristalográficas preferenciais (OCP), fornecem resultados que podem ser aplicados para uma explotação estratégica dos diferentes tipos de minérios, implicando na melhoria de áreas alvos. Este estudo foi focado na avaliação da correlação de microestruturas/texturas com parâmetros de flotação, visando otimizar o processo de flotação para aumentar a recuperação dos minérios pobres (ricos em sílica), que comumente contêm menos de 64% de Fe. Uma série de técnicas, incluindo difração por nêutrons, raios-X e elétrons retroespalhados (elétron backscattering difraction), bem como análises granulométricas e de imagens dos concentrados de flotação foram aplicados neste trabalho. Os resultados obtidos por meio das análises microestruturais e texturais, permitiram enquadrar os diferentes minérios no seu contexto tectônico, dentro do Quadrilátero Ferrífero. Adicionalmente, a diversidade reológica, obtida por várias técnicas resultou na definição de parâmetros de correlação com a flotação, que podem ser aplicados na indústria de beneficiamento, contribuindo para aumentar a recuperação do minério de ferro. / The wide range of minerals, microstructures and textures encountered in iron ores of the Quadrilátero Ferrífero region in Brazil, generates a diversity of physical properties with implications to its processing. The linking between rheology and deformation mechanisms which acted in microstructure and texture or crystallographic preferred orientations (CPO), formation provide results witch can be applied in strategic exploitation of different ore types, leading to the improvement of the selected targets. This study was focused in the evaluation and correlation of textures, microstructures with flotation parameters, aiming to optimize the flotation processing to increase the recovery of low-grade iron ores, which commonly contain less than 64% Fe. A series of techniques, including neutron diffraction, X-ray diffraction, electron backscattering diffraction as well as granulometric and imaging analysis of flotation concentrates were applied in this study. The results obtained through the textural and microstructural studies allow fitting different ores in your tectonic setting, into Quadrilátero Ferrífero. Additionally, the diversity of rheologic features defined by the different techniques led to define new correlation parameters with selectivity indices of flotation that can be applied to the iron ore processing industry, contributing to increase iron ore recovery.

A fusão zonal compreende uma família de métodos para controle e distribuição de impurezas na qual uma pequena zona fundida é deslocada lentamente ao longo de um material sólido, redistribuindo o soluto. Ela é utilizada na purificação de materiais, num processo denominado refino zonal, mas também pode ser usada na distribuição homogênea ou descontínua de impurezas e no crescimento de cristais. A fusão zonal aplicada ao crescimento de grãos, visando a obtenção de materiais mono ou policristalinos com grãos grosseiros é denominada recristalização por fusão zonal (ZMR) e seu uso principal é na preparação de materiais para fabricação de dispositivos eletrônicos e fotovoltaicos, especialmente em silício. Na última década, o progresso na tecnologia ZMR foi feito principalmente em três campos: desenvolvimento de equipamento, controle de processo e modelagem numérica, mas somente algumas pesquisas abordam a fusão zonal a baixas temperaturas e restringem a aplicação do método a outros materiais semicondutores como os elementos do grupo III, IV ou V. Deste modo, o presente trabalho tem como objetivo verificar a influência da velocidade de varredura, da largura da zona fundida e do número de passadas no processo de fusão zonal de materiais de baixo ponto de fusão, em relação à obtenção de materiais policristalinos com grãos grosseiros. Para tanto, construiu-se um equipamento de fusão zonal horizontal e barras de alumínio puro (P0610) foram submetidas ao processo, variando os parâmetros acima referidos. A macroestrutura das amostras foi analisada e os resultados obtidos do número de grãos/área foram interpretados, verificando a influência dos parâmetros físicos anteriormente citados, do gradiente térmico e do super-resfriamento constitucional. Verificou-se que a redução na velocidade de varredura e na largura da zona fundida, de modo geral, mostrou-se eficiente em relação à diminuição do número de grãos por área. Os resultados obtidos indicam que a fusão zonal foi efetiva na obtenção de alumínio policristalino com grãos grosseiros e colaboram para melhorar a compreensão do processo. / The zone melting comprises a family of methods to control and to distribute impurities in which a small molten zone is moved slowly along a solid material, redistributing solute. It is used in materials purification, in a so-called zone refining process, but can also be used in homogeneous or discontinuous distribution of impurities and crystal growth. The zone melting applied to grain enlargement, leading to attain singlecrystalline or polycrystalline materials with coarse grains is so-called zone melting recrystallization (ZMR) and its major use is the preparation of materials for electronic and photovoltaic devices process especially silicon. In the last decade, progress in ZMR technology was done mainly in three areas: equipment development, process control, and numerical modeling, but only a few researches handle on zone melting at low temperatures and it limits the application of the method to other semiconductor materials such as III, IV or V group elements. Thus, this study aims to examine the influence of scan rate, zone width and the number of zone passes in the zone melting process of low melting point materials about getting polycrystalline materials with coarse grains. For this, horizontal zone melting equipment was built and pure aluminum bars (P0610) were zone melted, varying the parameters mentioned above. The macrostructure of the samples was analyzed and the results of the number of grains per area were assessed by checking the influence of physical parameters previously mentioned and the thermal gradient and the constitutional supercooling. It was found that scan rate and zone width reduction in general, proved to be efficient in reducing the number of grains per area. The results indicate that the zone melting was effective in obtaining aluminum polycrystalline coarse-grained and collaborate to improve the understanding of the process.