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Yes / The shape memory effect of highly oriented long‐chain‐branched poly(lactic acid) (LCB‐PLA) prepared through solid‐phase die drawing technology was studied by comparison with PLA. When the recovery temperature increased from 60°C to 120°C, for PLA, only one‐step recovery at about 80°C can be observed and the recovery ratio was below 21.5%, while, for LCB‐PLA, multiple recovery behavior with high recovery ratio of 78.8% can be achieved. For oriented PLA, the recovery curve of the final sample showed the same trend with that of sample suffering just free drawing; while for oriented LCB‐PLA, the recovery curve of the final sample showed the same trend with that of sample suffering just die drawing. After shape recovery, the mechanical properties of LCB‐PLA showed a linear downward trend with the recovery temperature. Together with amorphous phase, the oriented mesomorphic phase, which formed during solid die drawing, can act as switching domains. And thus, upon heating, the chain segment of amorphous phase relaxed at first and triggered the first macroscopical shape recovery, leading to the decrease of long period (Lac) and the thickness of the amorphous layer (La). Then, with further increasing temperature, the oriented mesomorphic phase gradually relaxed resulting subsequently multi‐shape recovery, and the Lac and the La further decreased. Therefore, by regulating the recovery temperature of oriented LCB‐PLA, the shape recovery ratio and mechanical strength can be controlled effectively, and thus the self‐reinforced and self‐fastening effect can be achieved simultaneously for PLA as bone fixation material.

Pin1 (protein interacting with NIMA 1) is a peptidyl-prolyl isomerase involved in mitosis. As a potential anti-cancer drug target, Pin1 interacts and regulates the activity of an increasing number of cell cycle enzymes by an unknown mechanism. These cell cycle enzymes include Cdc25, Cdc27, Cyclin D1, Myt1, Wee1, NIMA, Cdc2, Plk1 and c-Myc. Recent research has revealed that Pin1 is overexpressed in a variety of cancer cell lines and Pin1 inhibitors inhibit proliferation activity of several cancer cells overexpressing Pin1. The most potent Pin1 inhibitors identified so far are in the micromolar range and no pharmacophore has been identified. In order to assist the understanding of the biological function of Pin1 using molecular probes, two amide isosteres of Ser-<i>trans</i>-Pro and Ser-<i>cis</i>-Pro dipeptides were designed and stereoselectively synthesized. The conformationally locked Ser–<i>trans</i>–Pro mimic, Boc-SerΨ[(<i>E</i>)CH=C]Pro–OH, was synthesized through the use of an Ireland-Claisen [3,3]-sigmatropic rearrangement in nine steps with 13% overall yield from a serine derivative. The Ser-<i>cis</i>-Pro mimic, Boc-SerΨ[(<i>Z</i>)CH=C]Pro–OH, was synthesized through the use of a Still-Wittig [2,3]-sigmatropic rearrangement in 11 steps with an overall yield of 20% from the same starting material. Conformationally locked peptidomimetics, including two exactly matched peptidomimetics, Ac–Phe–Phe–pSer–Ψ(<i>E</i>)CH=C]Pro–Arg–NH2 and Ac–Phe–Phe–pSer–Ψ[(<i>Z</i>)CH=C]Pro–Arg–NH2, were synthesized from these Ser-Pro isosteres using Fmoc SPPS. A protocol for in vitro Pin1 inhibition assay was established for measuring the inhibition constant for these peptidomimetics. A conformationally locked cis peptidomimetic inhibits Pin1 with a <i>K</i>_i of 1.7 <i>μ</i>M, 23-fold more potent than its trans counterpart, illustrating the preference of Pin1 for a cis amide bond in its PPIase domain. The A2780 ovarian cancer cell antiproliferation activity of these peptidomimetics parallels their respective Pin1 inhibition data. This research provides a start toward more drug-like Pin1 inhibitor design. Gly–<i>trans</i>–Pro isosteres were synthesized using the Ireland-Claisen route. The construction of a non-peptidic (Z)-alkene library for Pin1 inhibition was attempted using the Ser-<i>cis</i>-Pro mimic, Boc—SerΨ[(Z)CH=C]Pro–OH as the core. / Ph. D.

Pin1 is a peptidyl prolyl isomerase (PPIase) enzyme with two domains, the catalytic domain and the WW domain. Both domains specifically bind pSer/pThr–Pro motifs. Pin1 plays an important role in regulating the cell cycle, and it is involved in many diseases, such as cancer, HIV-1, Alzheimer's disease, asthma, hepatitis B, and rheumatoid arthritis. Pin1 is a very promising target for new drug development. Three stereoisomers: (R,S)-, (S,R)- and (S,S)-Ac–pSer–Ψ[(Z)CH=C]–Pip–2-(2-naphthyl)ethylamine were synthesized as inhibitors binding to the Pin1 catalytic domain. The (R,S)- and (S,R)-isomers were synthesized via a 13-step route, with overall yields of 2.0% and 1.4%, respectively. The newly formed stereogenic center in the piperidyl ring was introduced by a Luche reduction, followed by a stereoselective [2,3]-Still-Wittig rearrangement. The configuration of the stereocenter was determined by NOESY of a bicyclic derivative. The (Z)- to (E)-alkene ratio in the rearrangement was (5.5:1). The (S,S)-isomer was obtained as the epimerized by-product resulting from the (S,R)-isomer in the Na/NH3 deprotection step. The IC50 values for Pin1 inhibition were: 52, 85, and 141 μM, respectively. We concluded that in this Z-alkene isostere, the R-configuration would be preferred at both stereogenic centers, as mimics of L-Ser and L-Pip, to improve the affinity. Combinatorial chemistry is a powerful method to discover biologically active compounds, and solid-phase synthesis is most commonly used to synthesize combinatorial libraries. To identify ligands for the Pin1 WW domain, a library, R1CO–pSer–Pro–NHR2, was designed. A new solid-phase phosphorylating reagent (SPPR) containing a phosphoramidite function was synthesized in one step from commercially available Wang resin. The SPPR was applied in the preparation of a designed library through parallel synthesis. The library contained 357 members (17 Ã 21), and was screened by an enzyme-linked enzyme binding assay (ELEBA). The best hits were resynthesized, and the competitive dissociation constants, Kd-rel, were measured by ELEBA, with a Kd-rel value of 130 μM for the best ligand. The absolute dissociation constants will be measured by our collaborator, Prof. Jefferey Peng, University of Notre Dame, using NMR methods. Besides the identification of the Pin1 WW domain ligands, I created a practical method for solid-phase synthesis of phosphopeptides. / Ph. D.

BACKGROUND:The widespread utilization of organic compounds in modern society and their dispersion through wastewater have resulted in extensive contamination of source and drinking waters. The vast majority of these compounds are not regulated in wastewater outfalls or in drinking water while trace amounts of certain compounds can impact aquatic wildlife. Hence it is prudent to monitor these contaminants in water sources until sufficient toxicological data relevant to humans becomes available. A method was developed for the analysis of 36 trace organic contaminants (TOrCs) including pharmaceuticals, pesticides, steroid hormones (androgens, progestins, and glucocorticoids), personal care products and polyfluorinated compounds (PFCs) using a single solid phase extraction (SPE) technique with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). The method was applied to a variety of water matrices to demonstrate method performance and reliability.RESULTS:UHPLC-MS/MS in both positive and negative electrospray ionization (ESI) modes was employed to achieve optimum sensitivity while reducing sample analysis time (<20min) compared with previously published methods. The detection limits for most compounds was lower than 1.0 picogram on the column while reporting limits in water ranged from 0.1 to 15ng/L based on the extraction of a 1L sample and concentration to 1mL. Recoveries in ultrapure water for most compounds were between 90-110%, while recoveries in surface water and wastewater were in the range of 39-121% and 38-141% respectively. The analytical method was successfully applied to analyze samples across several different water matrices including wastewater, groundwater, surface water and drinking water at different stages of the treatment. Among several compounds detected in wastewater, sucralose and TCPP showed the highest concentrations.CONCLUSION:The proposed method is sensitive, rapid and robust / hence it can be used to analyze a large variety of trace organic compounds in different water matrixes.

The behaviour and impact of pharmaceuticals in the environment are still poorly understood. Pharmaceuticals are widely used and continually released into the environment causing increasing concerns about their impact on the environment beyond the intended human or veterinary use. Prescribed pharmaceuticals, typically, enter the environment either through excretion after human use or disposal of surplus medication. Sewage treatment plants do not completely remove pharmaceuticals and their metabolites and these have been detected in sewage treatment plant effluent and receiving waters. Land application of treated sewage effluent is widely practiced in New Zealand as an alternative to surface water discharge. Methods were developed to determine selected pharmaceuticals in environmental matrices such as sewage effluent, sewage solids, soil, and soil water. From these, pharmaceutical removal efficiencies were determined for three common sewage treatment processes; activated sludge, composting and land application of sewage effluent. The impacts of some common pharmaceuticals on soil microbial communities, together with the effect of prolonged exposure to sewage effluent on these communities were examined. Additionally, toxicity of sewage effluent, and toxicity mechanisms of specific pharmaceuticals were investigated using luminescent micro-organisms and lettuce seedlings. Pharmaceuticals were successfully detected in sewage effluent, sewage solids, compost, soil and soil water. The sewage treatment processes investigated, including land application, were able to remove or reduce pharmaceutical concentrations in sewage. In case of land application, volcanic soils were more efficient than sandy soils in pharmaceutical removal while irrigation rate and level of sewage pre-treatment also showed some effect on removal efficiency. Pharmaceuticals were not acutely toxic at environmental levels currently detected. Exposure of microbial communities to unnaturally high levels of pharmaceuticals did demonstrate that most pharmaceuticals were potentially able to induce stress in the microbial community although microbes were able to metabolise some of these pharmaceuticals. Twelve years of effluent irrigation resulted in microbial adaptation to aspirin, acetaminophen and tetracycline, indicating that these pharmaceuticals had an effect on microbial community. Presently, land application of treated sewage waste may be a suitable treatment for additional pharmaceutical removal provided that land application schemes are designed appropriately, and pharmaceutical accumulation in the soil is occasionally monitored. It would be prudent to recognise the potential risk that could be caused by chronic exposure to pharmaceuticals such that continued vigilance may lead to future indications of chronic effects at an early stage.

A fundamental theoretical and experimental study on calcium sulphate scale formation in hydrometallurgical solutions containing various minerals was conducted. A new database for the Mixed Solvent Electrolyte (MSE) model of the OLI Systems® software was developed through fitting of existing literature data such as mean activity, heat capacity and solubility data in simple binary and ternary systems. Moreover, a number of experiments were conducted to investigate the chemistry of calcium sulphate hydrates in laterite pressure acid leach (PAL) solutions, containing Al2(SO4)3, MgSO4, NiSO4, H2SO4, and NaCl at 25–250ºC. The database developed, utilized by the MSE model, was shown to accurately predict the solubilities of all calcium sulphate hydrates (and hence, predict scaling potential) in various multicomponent hydrometallurgical solutions including neutralized zinc sulphate leach solutions, nickel sulphate–chloride solutions of the Voisey’s Bay plant, and laterite PAL solutions over a wide temperature range (25–250°C). The stability regions of CaSO4 hydrates (gypsum, hemihydrate and anhydrite) depend on solution conditions, i.e., temperature, pH and concentration of ions present. The transformation between CaSO4 hydrates is one of the common causes of scale formation. A systematic study was carried out to investigate the effect of various parameters including temperature, acidity, seeding, and presence of sulphate/chloride salts on the transformation kinetics. Based on the results obtained, a mechanism for the gypsum–anhydrite transformation below 100°C was proposed. A number of solutions for mitigating calcium sulphate scaling problems throughout the processing circuits were recommended: (1) operating autoclaves under slightly more acidic conditions (~0.3–0.5 M acid); (2) mixing recycled process solutions with seawater; and (3) mixing the recycling stream with carbonate compounds to reject calcium as calcium carbonate. Furthermore, aging process solutions, saturated with gypsum, with anhydrite seeds at moderate temperatures (~80°C) would decrease the calcium content, provided that the solution is slightly acidic.

L’objectif de cette thèse est d’étudier le rôle de la fermentation malolactique (FML) sur l’arôme fruité des vins rouges. Les bactéries lactiques (BL) modifient la composition du vin mais il n’existe pas de consensus concernant spécifiquement cette famille aromatique. Contrairement aux idées empiriques sur la FML, ce travail a démontré l’absence à court terme d’un " masque lactique ", cependant l’apparition d’une telle interaction olfactive pourrait être plus tardive. Par contre, il est montré l’existence d’un masque proche de la note de réduction, de type fumé/grillé, dont la caractérisation n’a pas été effectuée dans cette étude.Le suivi des principaux marqueurs fruités du vin (70 molécules) a été rendu possible par le développement des méthodes d’analyse chromatographique en phase gazeuse couplée à la microextraction sur phase solide (esters, C13-norisoprénoïdes, lactones, thiols). En particulier, une " base de données esters " (32 composés) a rendu plus robuste l’ensemble des variations constatées au cours du développement des BL. En effet, les modifications des teneurs en esters sont démontrées comme un processus majeur de la balance de la note fruitée au cours de la FML. Cette fermentation permet à court terme, aussi bien la synthèse que l’hydrolyse des esters grâce aux activités estérases et, à plus long terme, la formation tardive d'esters éthyliques d'acides branchés issus du catabolisme de certains acides aminés. La spécificité des estérases vis-à-vis de la nature et de la longueur de la chaîne carbonée des esters est mise en évidence, ainsi que l'importance de la disponibilité des substrats, liée en partie à l'activité des levures.L’étude de l’influence des souches de BL et de la co-inoculation levures/bactéries a permis de confirmer le rôle clé des interactions entre les microorganismes, ainsi que l’importance de la composition de la matrice vin. / The aim of this thesis is to study the role of malolactic fermentation (MLF) on the fruity aroma of red wines. Lactic acid bacteria (LAB) modify wine composition but there is no consensus concerning this aromatic group specifically. In opposition to empirical ideas on MLF, this work has demonstrated the absence, in short-term, of a “lactic-mask” although this kind of olfactory interaction may still occur in a later stage of wine development. Nevertheless, the existence of a smoked/toasted reduction-like mask note was proved. Its characterization has not been done in this work. The survey of the main fruity markers of wine (70 compounds) was made possible by the development of several gas chromatography coupled with solid-phase microextraction analytical methods (esters, C13-norisoprenoids, lactones, thiols). In particular, the creation of an “ester database” (32 compounds) has improved the detection of variations during LAB development in terms of analysis robustness. In fact, changes on esters contents are proved to be responsible for a major part of fruity notes evolution during MLF. Initially, this fermentation allows both synthesis and hydrolysis of esters as a consequence of esterase activity. Moreover, it promotes late-production of ethylic esters through the catabolism of certain aminoacids. Esterases specificity towards nature and size of the esters carbon chain is pointed out along with substrates availability, partially related to yeast activity.The study of the influence of both LAB strains and yeast/bacteria co-inoculation has confirmed microorganisms interactions and wine matrix composition to be of the great importance.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Les évolutions de microstructures du nouvel alliage chinois Ti B19 ont été étudiées au cours de divers traitements thermiques et des relations entre microstructures et propriétés mécaniques ont été établies. Les cinétiques de transformations isothermes ont été établies par des mesures de résistivité électrique. Les structures et microstructures ont été caractérisées par DRX synchroton, Microscopies Optiques et Electroniques (MEB, MET). Les cinétiques de transformation et les caractéristiques microstructurales. Les cinétiques de transformation isothermes ont été obtenues, analysées (loi JMAK), et cet ensemble de résultats a conduit à l'établissement du diagramme TTT de l'alliage TiB19. Enfin il a été montré que la vitesse de chauffage a une très forte influence sur les transformations mises en jeu, et qu'une pré déformation plastique accélère les cinétiques de transformation (introduction de nouveaux sites de germination). Enfin les cinétiques de transformation ont été caractérisées en refroidissement continu depuis le domaine monophasé bêta. Une première approche de la modélisation des cinétiques de transformation a été menée en utilisant le loi JMAK et le principe d'additivité de Scheil. Enfin les relations entre microstructures et propriétés sont discutés / The phase transformations and microstructure evolutions has been characterized for different thermal treatments, and the relationships between final microstrures and properties have been investigated in the new metastable Ti-B19 alloy. The isothermal phase transformation kinetics and the influence of different heat treatment phaths have been establisheb by using in-situ electrical Resistivity. The structures have been determined by synchrotron X-Ray Diffraction and the microstructures were observed by SEM and TEM. The results show that phase transformation kinetics and microstructure characteristics are strongly dependent on the aging temperature (ranging from 300 to 700°C). The global isothermal phase transformation phase transformation kinetics has been got and anallyzed with JMAK equation, and the TTT diagram of Ti-B19 alloy has been established. We have also shown that the heating rate has remarkable influence on the isothermal phase transformation behaviors and the pre-deformation accelerates the transformation kinetics. The microstructure evolutions during cooling are obviously dependent on the cooling rates. A first attempt has been made to calculate the transformation kinetics during cooling using JMAK law and Scheil principle. Finally, the relationship between mechanical properties and microstructure has been discussed