The goal of our research is to generate cryopreservation agents derived from antifreeze glycoproteins. One postulated mechanism of cell cryo-injury is ice recrystallization. It is known that simple saccharides and cryopreservation agents (DMSO) display ice recrystallization inhibition (IRI). This study assessed the cytotoxicity and cryopreservation ability of these sugars in relation to their IRI. It was determined that compounds with greater IRI have increased cytotoxicity yet confer cryoprotection. To further investigate how structure is affecting IRI activity, several galactopyranoside derivatives were synthesized. A series of deoxy and α-Callyl- deoxy galactopyranoses were prepared. Testing determined that removal of any hydroxyl group removes IRI. 3-deoxy-β-thiophenyl galactose was also synthesized and had surprisingly better IRI than β-thiophenylgalactose. Also, 6-azido galactose had similar IRI to 6-deoxy galactose. Lastly, a series of β- thioalkylgalactosides was synthesized and testing gave contradicting results which suggest that predicting IRI based on hydrophilicity is more complicated than initially hypothesized.

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.

When a water soluble granular fertilizer, such as potash, is wetted and then dried during storage and transportation processes, clumps or cakes often form in the material even when the maximum moisture content is less than 1% by mass. In order to avoid or decrease these occurred cakes, it is essential to characterize cake strength and to explore the process of cake formulation or caking through theoretical/numerical analysis. In this thesis, both experimental measurements of cake strength and theoretical/numerical simulations for recrystallization near a contact point are used to investigate the relationship between the caking process and the cake strength for important factors such as initial moisture content and drying time. <p>In this research, a centrifugal loading method has been developed to determine cake strength in a caked ring specimen of potash fertilizer where internal tensile stresses dominate. Research on fracture mechanics states that brittle materials, such as caked potash, fail at randomly positioned fracture surfaces in tension so the centrifuge test method is well suited to provide good data. A two-dimensional plane stress analysis was used to determine the area-averaged tensile stress at the speed of the centrifuge when each specimen fractures. Repeated tests and uncertainty calculations give data with a narrow range of uncertainty. <p>The centrifuge test facility was used for a series of tests in which the initial moisture content, drying time, particle size and chemical composition (i.e. magnesium content) of the samples were varied. For particle sizes in the range from 0.85 to 3.35 mm, experimental data show that the cake strength increased linearly with initial moisture content for each drying method and particle size, and decreased with increasing particle size for each initial moisture content and drying method. As well, it was also found that cake strength will increase essentially linearly with magnesium content from 0.02% to 0.1% for samples with the same initial moisture content, particle size and drying method. All data show that potash samples tend to form a stronger cake with a slower drying process. <p>A theoretical/numerical model is presented in this thesis to simulate ion diffusion and crystallization near one contact point between two potash (KCl) particles during a typical drying process. The effects of three independent factors are investigated: initial moisture content; evaporation rate; and degree of supersaturation on the surface surrounding the contact point. The numerical results show that the mass of crystal deposition near the contact point will increase with increased initial moisture content and decreased evaporation rate. These numerical predictions for recrystallization near the contact point are consistent with the experimental data for the cake strength of test samples of particle beds. With variations in the solid crystal surface degree of supersaturation near the contact point, simulations showed up to 5 times the increase in the crystal mass deposition near the contact point. This prediction of increased roughness is consistent with another experimental investigation which showed that the surface roughness of NaCl and KCl surfaces increased by a factor of five after one wetting and drying process.

The goal of our research is to generate cryopreservation agents derived from antifreeze glycoproteins. One postulated mechanism of cell cryo-injury is ice recrystallization. It is known that simple saccharides and cryopreservation agents (DMSO) display ice recrystallization inhibition (IRI). This study assessed the cytotoxicity and cryopreservation ability of these sugars in relation to their IRI. It was determined that compounds with greater IRI have increased cytotoxicity yet confer cryoprotection. To further investigate how structure is affecting IRI activity, several galactopyranoside derivatives were synthesized. A series of deoxy and α-Callyl- deoxy galactopyranoses were prepared. Testing determined that removal of any hydroxyl group removes IRI. 3-deoxy-β-thiophenyl galactose was also synthesized and had surprisingly better IRI than β-thiophenylgalactose. Also, 6-azido galactose had similar IRI to 6-deoxy galactose. Lastly, a series of β- thioalkylgalactosides was synthesized and testing gave contradicting results which suggest that predicting IRI based on hydrophilicity is more complicated than initially hypothesized.

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.

Microstructural evolution in a naturally-aged and cold-rolled AA6451 aluminum alloy during a non-isothermal annealing process, which leads to significant grain refinement, is investigated through: (a) conducting a comprehensive experimental analysis and (b) developing a computational modeling technique. The underlying mechanisms of annealing have been investigated through analysing interactive phenomena between precipitation and concurrent recovery and recrystallization. It is shown that the interactions between solute elements, clusters, and fine precipitates with dislocations restrict dynamic and static recovery during deformation and subsequent annealing. Inhibition of recovery favours recrystallization that initiates at 300oC and progresses through a nucleation and growth mechanism. Despite localized inhomogeneities, nucleation mainly occurs in non-recovered high energy sites which are uniformly distributed within the entire structure. Growth of the recrystallized nuclei is restricted by pinning precipitates that undergo a concurrent coarsening process. The fine, uniform distribution of recrystallized nuclei and their limited growth result in the formation of a fine-grained microstructure, after completion of recrystallization. The acquired knowledge has been used to develop a computational modeling technique for simulating microstructural evolution of the alloy. Microstructural states are simulated by integrating analytical approaches in a Monte Carlo algorithm. The effects of deformation-induced and pre-existing inhomogeneities, as well as precipitate coarsening and grain boundary pinning on the competitive recovery-recrystallization process are included in the simulation algorithm. The developed technique is implemented to predict the microstructural evolution during isothermal and non-isothermal annealing of AA6xxx sheets. A good quantitative agreement is found between the model predictions and the results from the experimental investigations.

When a water soluble granular fertilizer, such as potash, is wetted and then dried during storage and transportation processes, clumps or cakes often form in the material even when the maximum moisture content is less than 1% by mass. In order to avoid or decrease these occurred cakes, it is essential to characterize cake strength and to explore the process of cake formulation or caking through theoretical/numerical analysis. In this thesis, both experimental measurements of cake strength and theoretical/numerical simulations for recrystallization near a contact point are used to investigate the relationship between the caking process and the cake strength for important factors such as initial moisture content and drying time. <p>In this research, a centrifugal loading method has been developed to determine cake strength in a caked ring specimen of potash fertilizer where internal tensile stresses dominate. Research on fracture mechanics states that brittle materials, such as caked potash, fail at randomly positioned fracture surfaces in tension so the centrifuge test method is well suited to provide good data. A two-dimensional plane stress analysis was used to determine the area-averaged tensile stress at the speed of the centrifuge when each specimen fractures. Repeated tests and uncertainty calculations give data with a narrow range of uncertainty. <p>The centrifuge test facility was used for a series of tests in which the initial moisture content, drying time, particle size and chemical composition (i.e. magnesium content) of the samples were varied. For particle sizes in the range from 0.85 to 3.35 mm, experimental data show that the cake strength increased linearly with initial moisture content for each drying method and particle size, and decreased with increasing particle size for each initial moisture content and drying method. As well, it was also found that cake strength will increase essentially linearly with magnesium content from 0.02% to 0.1% for samples with the same initial moisture content, particle size and drying method. All data show that potash samples tend to form a stronger cake with a slower drying process. <p>A theoretical/numerical model is presented in this thesis to simulate ion diffusion and crystallization near one contact point between two potash (KCl) particles during a typical drying process. The effects of three independent factors are investigated: initial moisture content; evaporation rate; and degree of supersaturation on the surface surrounding the contact point. The numerical results show that the mass of crystal deposition near the contact point will increase with increased initial moisture content and decreased evaporation rate. These numerical predictions for recrystallization near the contact point are consistent with the experimental data for the cake strength of test samples of particle beds. With variations in the solid crystal surface degree of supersaturation near the contact point, simulations showed up to 5 times the increase in the crystal mass deposition near the contact point. This prediction of increased roughness is consistent with another experimental investigation which showed that the surface roughness of NaCl and KCl surfaces increased by a factor of five after one wetting and drying process.

Non-isothermal crystallization of the PET/PTT copolyesters was studied at five different cooling rates over 1-20oC/min by means of differential scanning calorimetry (DSC). Both the Ozawa equation and the modified Avrami equation have been used to analyze the crystallization kinetics. The non-isothermal kinetics of most copolymers cannot be described by the Ozawa analysis, except the copolyester with a composition of 66.3% trimethylene- (TT) and 33.7 %ethylene- terephthalates (ET). It may be due to the inaccuracy of the Ozawa assumptions, such as the secondary crystallization is neglected. From the kinetic analysis using the modified Avrami equation, the Avrami exponents, n, were found to be in the range of 2.43-4.67 that are dependent on the composition of the copolyesters. The results indicated that the primary crystallization of the PET/PTT copolymers followed a heterogeneous nucleation and a spherulitic growth mechanism during the non-isothermal crystallization. In the cases of the copolyesters with either TT or ET less than 10%, we found the molten temperature is a key factor to decide whether the Ozawa equation can be succeeded in analyzing the dynamic crystallization. For the non-isothermal crystallization, a single exothermic peak was detected in each DSC curve regardless of the composition and the cooling rate. It indicated that a single-mode distribution of the crystallite sizes was formed during the cooling process. After the non-isothermal crystallization, the melting behavior of the specimens was monitored by temperature modulated DSC (TMDSC) in the conventional mode and the modulated mode. Multiple endothermic peaks were observed in both modes. The wide-angle X-ray diffraction (WAXD) patterns of these copolymers showed that the peak height became sharper and sharper as the crystallization temperature increased, but the position of the diffraction peaks did not change apparently. It indicated that the multiple melting behaviors did not originate from the melting of the crystals with different structures. The melting behavior of these PET/PTT copolyesters can be explained logically by using the melt-recrystallization model. From the reversing and non-reversing signals of TMDSC, the melting-recrystallization-remelting phenomena were further verified. In addition, a small endothermic peak was found at the highest melting temperature in the reversing thermogram for TT-enriched copolyesters. It is reasonably to believe that this endotherm is attributed to the melting of the crystals that are formed in regime I during the heating scan. The cocrystallization of the PET/PTT copolyesters was studied using DSC and WAXD. A clear endothermic peak in the DSC thermogram was detected over the entire range of copolymer composition. A minimum melting temperature was found for the copolyester with 50% ET. The WAXD patterns of these copolymers can be divided into two groups with sharp diffraction peaks, i.e., PET type and PTT type crystals. The transition of crystal structure between PET type and PTT type occurred around the eutectic composition (50 % ET and TT), determined from the variation of the melting temperature with the composition. In addition, the fiber diagram and the WAXD pattern of the copolyester with the eutectic composition showed a different crystalline structure. These results indicated that the cocrystallization behavior of the PET/PTT copolyesters was isodimorphic.

The primary objectives of this study were: (1) to verify the effectiveness of ECAE to induce equal amounts of strain and grain refinement in bars of different cross-sectional areas, (2) to determine the effectiveness of ECAE in breaking down the as-cast macrostructure in CDA 101 Cu and in producing a homogeneous material containing micron-scale grains upon recrystallization, and (3) to determine a thermomechanical processing (TMP) schedule (from the ones examined) that produces the best microstructure in terms of grain size and uniformity. The effects of extrus ion route, levels of strain and intermediate heat treatment were investigated. To achieve the first objective, bars having square cross-sections of three different sizes, 19 mm, 25 mm and 50 mm, were processed up to eight ECAE passes through routes A, B, C and E. To achieve the second and third objectives, bars were processed up to eight ECAE passes with and without intermediate heat treatments through routes Bc, C, E and F. ECAE processing was carried out in a 90o extrusion die with sliding walls at an extrusion speed of 2.5 mm/s. Recrystallization studies were carried out on the processed material to evaluate the recrystallization behavior and thermal stability of the material. The as-worked and recrystallized materials were characterized by Vickers microhardness, optical microscopy (OM) and transmission electron microscopy (TEM). Results indicate that similar hardness values, sub-grain morphology and recrystallized grain size are generated in the three bars having different cross-sectional sizes processed through ECAE. ECAE is shown to induce uniform strain in all three billet sizes. ECAE is therefore shown to be effective in scale-up to a size of at least 50 mm, with larger billets giving better load efficiency. Results from the later parts of this study indicate that eight extrusion passes via route Bc produces the best microstructure in terms of grain size and microstructural uniformity. The routes can be arranged in the sequence Bc> E, F> C for their ability to produce a uniform recrystallized microstructure with small average grain size. Macroscopic shear bands are sometimes generated during extrusion depending upon the initial grain morphology and texture of the material.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第18987号 / 工博第4029号 / 新制||工||1620 / 31938 / 京都大学大学院工学研究科材料工学専攻 / (主査)教授 辻 伸泰, 教授 白井 泰治, 教授 松原 英一郎 / 学位規則第4条第1項該当