The topics of this study are as follows: (a) Poly(butylene succinate) (PBSu) rich random copolymers containing ~20% and ~50% trimethylene succinate (TS), PBTSu 80/20 and PBTSu 50/50 that were synthesized from 1,4-butanediol, 1,3-propanediol and succinic acid: The influence of minor TS units on the thermal properties and crystallization rate of PBSu was investigated. (b) Random copolymer of ~90% PBSu and ~10% poly(1,4-cyclohexanedimethylene succinate), PBCHDMSu 90/10, that was synthesized from 1,4-butanediol, 1,4-cyclohexanedimethanol and succinic acid: The influence of cyclohexene unit on the thermal properties and crystallization rate of PBSu was investigated. (c) Blends of PBSu and poly(trimethylene succinate) (PTSu) or poly(ethylene succinate) (PESu): The weight ratio PBSu and PTSu (or PESu ) were 1:1. The crystallization and morphology of blends (PBSu/PTSu 50/50 and PBSu/PESu 50/50) were investigated and compared with PBTSu 50 and PBESu 50/50. The chemical composition and the sequence distribution of co-monomers in copolyesters were determined using NMR. Thermal properties of polyesters and blends were characterized using differential scanning calorimeter (DSC) and temperature-modulated DSC (TMDSC). The crystallization kinetics and equilibrium melting temperature were analyzed with Avrami equation and Hoffman-Weeks linear extrapolation. The thermal stability of polyesters was analyzed by thermogravimeter (TGA) and polarized light microscope (PLM) under nitrogen. Wide-angle X-ray diffractograms (WAXD) were obtained for specimens after complete isothermal crystallization. The growth rates, regime transition temperature, morphology and phase separation were studied using polarized light microscope (PLM) with isothermal method or nonisothermal method. The morphology of specimens after chemical etching were investigated using atomic force microscope (AFM) and scanning electron microscope (SEM). The distribution of butylene succinate (BS) and TS units in PBTSu 80/20 was found to be random from the evidence of a single Tg and a randomness value close to 1.0 for a random copolymer. With the increasing of minor amounts of comonomers, the sequence length of butylene succinate decreases, and the crystallization rate and the degree of crystallinity drop. DSC heating curves of isothermal crystallized PBTSu 80/20 and PBCHDMSu 90/10 showed triple melting peaks. Multiple melting behaviors indicate that the upper melting peaks are associated with the primary and the recrystallized crystals, or the crystals with different lamellar thickness. As the Tc increases, the contribution of recrystallization slowly decreases and finally disappears. Hoffman-Weeks linear plots gave an equilibrium melting temperature of 113.5

This study contains four main parts. Part 1, poly(butylene succinate) (PBSu) rich random copolymers containing ~20% 2-methyl-1,3-propylene succinate (MPS), PBMPSu 80/20. The influence of minor MPS units on thermal properties and crystallization rate was investigated. Part 2, poly(butylene succinate) (PBSu) rich random copolymers containing ~5% 1,4-cyclohexanedimethylene succinate (CHDMS), PBCHDMSu 95/5. The influence of cyclohexane unit on thermal properties and crystallization rate was investigated. Part 3, Poly(butylene succinate) (PBSu) random copolymers containing ~50% 2-methyl-1,3-propylene succinate (MPS), PBMPSu 50/50. Blend of PBSu with poly(2-methyl-1,3-propylene succinate) (PMPSu). The weight ratio of PBSu and PMPSu were 1:1. The crystallization behavior and morphology was compared. Part 4, Poly(ethylene succinate) (PESu) random copolymers containing ~50¢H trimethylene succinate (TS), PETSu 50/50. Blend of PESu with poly(trimethylene succinate) (PTSu). The weight ratio of PESu and PTSu were 1:1. The crystallization behavior and morphology was compared. Molecular weights of copolymers were measured using capillary viscometer and gel permeation chromatography (GPC). The results indicate that polyesters used in this study have high molecular weights. The chemical composition and the sequence distribution of co-monomers in copolyesters were determined using 1H NMR and 13C NMR. The distribution in these copolyesters was found to be random from the evidence of a randomness value close to 1.0 for a random copolymer. Thermal properties of blends and copolyesters were characterized using differential scanning calorimeter (DSC) and thermogravimeter (TGA). The crystallization kinetics and mleting behaviors was analyzed after isothermal crystallization by DSC. Wide-angle X-ray diffractograms (WAXD) were obtained for specimens after complete isothermal crystallization. The growth rates, morphology were studied using polarized light microscope (PLM). The morphology of specimens after chemical etching was investigated using scanning electron microscope (SEM) and atomic force microscope (AFM). AS the ratio of MPS units increase, the degree of crystallinity and crystallization rate drop, it was due to decrease of butylene succinate sequence length. The spherulite growth rate of PBCHDMSu 95/5 is much slower compare with PBSu rich copolymers containing 5% TS or MPS. It was due to the steric effect of cyclohexane unit in the polymer chains. The crystalline morphology of PBMPSu 50/50 and PETSu 50/50 were quite different. It was due to the short sequence length of butylene succinate and ethylene succinate. From the analysis results by DSC and observation by PLM and SEM, it indicates that PBSu was miscible with PMPSu while PESu was partial miscible with PTSu.

Poly(ethylene succinate) (PES), poly(trimethylene succinate) (PTS) and their copolyesters with various compositions were synthesized through a direct polycondensation reaction with titanium tetraisopropoxide used as the catalyst. Results obtained from intrinsic viscosity and gel permeation chromatography (GPC) studies have significantly contributed to the preparation of polyesters with high molecular weight. Compositions and sequence distributions of the synthesized copolyesters were determined by analyzing the spectra of 1H NMR and 13C NMR. According to those results, the sequence distributions of ethylene succinate (ES) units and trimethylene succinate (TS) units were found to be random. Thermal properties were then characterized using differential scanning calorimeter (DSC) and thermogravimetric analyzer (TGA). All copolymers exhibited a single glass transition temperature (Tg). These polyesters did not significantly differ in thermal stability. Next, thermal stability was estimated using polarized light microscopy (PLM). Isothermal growth rates for polyesters were observed after pre-melting at various temperatures. The thermal degradation temperature (Td) was estimated, at which the growth rate for polyesters increased abruptly. The Td value of PES and PETSA 95/05 was found to be 213 and 200 ¢XC, respectively, which was 35−45 ¢XC lower than that determined by TGA. Wide-angle X-ray diffractograms (WAXDs) were obtained for polyesters that were crystallized isothermally at a temperature 5−10 ¢XC below their melting temperatures. Only the crystal form of PES was appeared in the diffractograms of PES-rich copolyesters. The TS units in polyesters may be excluded and located in the amorphous part of polyesters. WAXD results indicate that incorporating TS units into PES could significantly inhibit the crystallization behavior of the latter. Additionally, dynamic mechanical properties of moldable polyesters were investigated using a Rheometer operated at 1 Hz. Below Tg, incorporating TS units into PES led to a decline in the storage modulus, while above Tg, the effect of crystallinity on the storage modulus could be found. The sphreulite growth rates for crystallizable polyesters were measured by PLM. The growth rate of polyesters decreased with an increasing moiety of TS units. The regime II¡÷III transition of PES was estimated to occur at ca. 71 ¢XC, which is extremely close to values in the literature. The regime transition of PETSA95/05 and PETSA 80/20 was found to be 65.0 ¢XC and 51.4 ¢XC, respectively. A dynamic crystallization experiment was performed by PLM and compared with time consuming isothermal experiments. Above data closely corresponded to those data points determined in the isothermal experiments. Results of the regime analysis for the continuous data of polyesters closely resembled those of isothermal experiments. The maximum growth rate was formulated in Arrhenius and WLF expressions for the molecular transport term. A master curve of the crystal growth rate for PES was constructed based on the continuous data of PES. Plotting the reduced growth rates after normalization against the reduced temperatures revealed a universal master curve for PES and two PES-rich copolyesters. Finally, the lateral surface free energy, fold surface free energy and work for chain folding of polyesters were evaluated based on kinetic analysis. According to those results, the works for chain folding decreased with an increasing moiety of TS units.

The search for anticancer drugs that are tumor specific and cause minimal side effects and the development of effective cancer vaccines are focal points of cancer therapy today. Dendritic cells (DC) are considered potential candidates for cancer immunotherapy due to their ability to process and present antigens to T cells and stimulate immune responses. However, DC-based vaccines have exhibited minimal effectiveness in abrogating established tumors in mice and human cancer patients. The use of appropriate adjuvants can enhance the efficacy of DC-based cancer vaccines in treating established tumors.The studies in this dissertation describe a chemo-immunotherapeutic strategy, which combines a Vitamin E analog, a-tocopheryl succinate (a-TOS) that is selectively toxic to tumor cells with non-antigen pulsed, non-matured dendritic cells (nmDC) to treat established murine lung and breast tumors. The results demonstrate that a-TOS synergizes with nmDC to inhibit the growth of established tumors and significantly reduce residual lung metastasis when therapy is initiated after surgical removal of primary tumors. This outcome was correlated with increased IFN-g and IL-4 production by splenic and draining lymph node lymphocytes. In trying to understand the mechanism of action of the combination treatment we observed that a-TOS treated tumor cells factors cause DC maturation in vitro. This effect is mediated in part by heat shock proteins 60, 70 and 90 induced during a-TOS-mediated killing of tumor cells. This study demonstrates the potential usefulness of a-tocopheryl succinate, an agent non-toxic to normal cell types, as an adjuvant to augment the effectiveness of DC-based vaccines in treating cancer.

Inaug.-diss.--Strassburg.

Inaug.-diss.--Strassburg.

Although the importance of tricarboxylic acid cycle activity in the metabolism of aerobic bacteria is well established, detailed studies on the utilization of intermediates of the cycle designed to assess the nature, importance and control of the enzymes concerned have not been performed with pseudomonads. Results of this investigation have shown that Pseudomonas aeruginosa ATCC 9027 lacks NAD or NADP linked L-malic dehydrogenase. Studies with cell fractions have shown that an NAD and NADP independent, particulate L-malic dehydrogenase catalyses the oxidation of L-malic acid to oxalacetic acid. The labelling patterns of citrate obtained from succinate-1,4-¹⁴ C and succinate-2,3-¹⁴ C have demonstrated the involvement of the particulate malic dehydrogenase and have excluded any other possibility. Phosphofructokinase could not be detected in the cell-free extract preparations and thus accounting for the non-functional Embden-Meyerhof pathway in this organism. Cells grown in succinate medium either do not have or have extremely low levels of glucose metabolizing enzymes. The glucose effect on tricarboxylic acid cycle enzymes was not observed. Further, the addition of α-keto- glutarate and glutamate to the medium did not repress these enzymes. These observations suggest that tricarboxylic acid cycle activity is of special importance for growth and metabolism in pseudomonads. The data have also indicated that during growth in a succinate medium, pentose synthesis must occur by the action of transketolase upon compounds derived from tricarboxylic acid cycle intermediates. It has been shown that both the glucose permease and the glucose metabolizing enzymes were induced simultaneously on shift from succinate to glucose medium. The glucose permease was found to be very specific since glucose uptake was not inhibited even in the presence of 100-fold excess of α-CH glucoside, 2-deoxyglucose, galactose, fructose or mannose. Particulate malic dehydrogenase was inhibited by adenine nucleotides while it was activated by GTP and GDP. The mechanism of this regulation is not clear, however, it is obviously important in the control of tricarboxylic acid cycle activity. Addition of glutamate to the medium repressed the synthesis of glutamic dehydrogenase. High levels of malic enzyme were maintained on growth in glucose and succinate media, whereas the levels were low in acetate medium. These observations demonstrated the capacity of the organism to regulate the synthesis of enzymes in response to the particular environment. Tricarboxylic acid cycle intermediates and glyoxylate have been found to exert "fine control" over the activities of isocitrate dehydrogenase and isocitrate lyase in such a way that flow of isocitrate through the tricarboxylic acid cycle and the glyoxylate cycle is precisely regulated to suit the needs of the cell. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

Titre de l'écran-titre (visionné le 11 janvier 2024) / Le but de ce projet est de concevoir un nouveau composite de type « bois-plastique » à base de poly(succinate de butyle) (PBS) et de fibres d'érable. La fibre d'érable provient d'un rejet de l'industrie forestière sous forme de poudre, tandis que la résine PBS (vierge) est disponible sous forme de granulés. Les échantillons de composite sont produits selon la méthode d'extrusion puis moulés à l'aide d'une presse à injection. Le travail se décompose en trois parties. La première partie étudie l'effet de la concentration de fibres d'érable (0 à 40% en poids) dans le composite. Selon les résultats de caractérisations obtenus (mécanique, physique et morphologique), la deuxième partie étudie l'effet de la concentration (0 à 15% en poids) d'un agent couplant commercial (polypropylène greffé d'anhydride maléique, MAPP). Finalement, la troisième partie étudie le comportement au recyclage mécanique en boucle fermée pour le composite optimisé (30% de fibres d'érable et 10% d'agent couplant). Comme conclusion principale, on observe que le composite a vu ses propriétés augmenter à l'aide de l'agent couplant mais pas de façon significative. Il présente néanmoins une bonne conservation de ses propriétés au recyclage. Cette étude aura permis de montrer que la méthode d'extrusion fonctionne pour le composite à base de PBS et de fibres de bois. Cependant, il faudra revoir la partie de compatibilisation matrice/renfort pour le futur. / The goal of this project is to design a new wood-plastic composite based on poly(butyl succinate) (PBS) and maple fibres. Maple fibres are residues from the forest industry in a powder form, while PBS (virgin) is available in pellets. The composites are produced using extrusion and then molded via injection molding. The work is divided into three parts. The first part studies the effect of maple fibers concentration (0 to 40% by weight) in the composite. Based on the characterization results obtained (mechanical, physical and morphological), the second part studies the effect of the concentration (0 to 15% by weight) of a commercial coupling agent (polypropylene grafted with maleic anhydride, MAPP). Finally, the third part studies the behavior under mechanical recycling in a closed loop for the optimized composite (30% maple fibers and 10% coupling agent). As a main conclusion, it is observed that the composite has better properties with the addition of the coupling agent, but not significantly. Nevertheless, it retains its properties in recycling. This study shows that extrusion works well for composites based on PBS and wood fibers. However, it will be necessary to review the matrix/reinforcement compatibility part in future work.

De par ses propriétés thermomécaniques proches des polyoléfines, le poly(butylene succinate)est l’un des polymères biosourcés les plus attractifs pour la substitution de matériaux pétro-sourcés pour des applications automobiles. L’incorporation de fibres de chanvre, via une étape d’extrusion,renforce la matrice et permet de tendre vers les propriétés cibles exigées par les cahiers des charges automobiles pour les applications visées dans cette étude. Afin d’améliorer les propriétés thermomécaniques de ce matériau, trois sujets ont été développés dans cette étude :1- Qualification de l’interface PBS / fibres de chanvre : via une nouvelle méthodologie basée sur l’analyse de la contribution effective des fibres sur la contrainte (CFC) durant une sollicitation mécanique, il est montré que les liaisons hydrogène formées entre le PBSet la fibre influent fortement sur les mécanismes de transfert de charge. Couplée au modèle de Bowyer et Bader, cette approche permet d’identifier les mécanismes d’endommagement de l’interface et de quantifier la contrainte interfaciale (τchanvre/PBS=25,2MPa).2 - Signification du ratio L/D d’une fibre naturelle : au cours des procédés de mises en oeuvre (extrusion et injection), la morphologie d’une fibre végétale évolue et apparait complexe due à la structure branchée engendrée par la fibrillation. A partir d’une nouvelleméthodologie d’analyse d’images spécifiquement développée, il est montré que la fibrillation contribue au renforcement de la matrice au même titre que le défibrage.3 -Synthèse de PBS-co-amides : afin de couvrir les contraintes thermomécaniques exigées,l’introduction de groupements amide dans le PBS est étudiée pour augmenter le point de fusion du polymère. Afin de contourner notamment la réaction parasite de cyclisation entre l’acide succinique et les amines, une stratégie de synthèses multi-étapes de monomères et de poly(ester-amide) est étudiée permettant d’obtenir un PEA de faible masse molaire dont le point de fusion atteint 172°C. / With its thermomechanical properties closed to polyolefins, poly(butylene succinate) is one ofthe most interesting bio-based polymers for substitution of oil-based polymers for automotive applications. Addition of hemp fibers, through an extrusion process step, reinforces matrix and enables to fit with the targeted technical profile required by automotive specifications. In order to improve thermomechanical properties, three main topics have been investigated in this study:1 - PBS / hemp fibers interface qualification: through a new methodology based on the analysis of the effective fiber contribution on stress during mechanical solicitation, it was shown that hydrogen bonds between PBS and fibers play a major role in load transfer.Combined with the Bowyer and Bader model, this approach enables to highlight interface damages and to determine the interfacial shear strength (τhemp/PBS=25,2 MPa)2 - Meaning of natural fiber L/D ratio: during processes (extrusion and injection), vegetal fiber morphology changes and becomes complex due to the fibrillated structure. With anew developed image analysis tool, it was shown that fibrillation contributes to matrix einforcement as well as defibering.3 - Synthesis of PBS-co-amide: to reach the targeted thermomechanical performances,introduction of amide groups into PBS was studied to increase the melting point. In order to avoid the cyclic imide formation between succinic acid and amines, synthesis of monomers and poly(ester amide) were studied through a multistep strategy, enabling to get low molecular weight PEA with melting temperature around 172°C.

Three series copolyesters [poly(butylene succinate-co-propylene succinate) (PBPSu), poly(butylene succinate-co-2-methyl-1,3-propylene succinate) (PBMPSu) and poly(ethylene succinate-co-butylene succinate) (PEBSu)] and their homopolyesters [poly(butylene succinate) (PBSu), poly(ethylene succinate) (PESu), poly(propylene succinate) (PPSu) and poly(2-methyl-1,3-propylene succinate) (PMPSu)] were synthesized by a two-step reaction (esterification and polycondensation) with titanium tetraisopropoxide as the catalyst. Molecular weights of all synthesized polyesters were determined by intrinsic viscosity and gel permeation chromatography (GPC) measurements. The values of intrinsic viscosity (0.97 ~ 1.62 dL/g) and relative molecular weight (2.4x10000 ~ 11.9x10000 g/mol) indicate that these polyesters can be made into films without complications. Compositions and sequence distributions of copolyesters were determined by analyzing the spectra of 1H NMR and 13C NMR. The randomness values of these copolyesters are closed to 1.0 that represents random sequence distribution of the comonomers. Thermal properties and stabilities were characterized using differential scanning calorimeter (DSC) and thermogravimetric analyzer (TGA), respectively. All copolyesters exhibited a single glass transition temperature (Tg). For PBPSu copolyesters, incorporating propylene succinate units to PBSu not only narrows the window between Tg and melting temperature (Tm), but also retards the cold crystallization ability, thereby lowering the crystallinity to a considerable extent. This phenomenon also occurred in PBMPSu and PEBSu copolyesters when the 2-methyl-1,3-propylene succinate (MPS) and butylene succinate (BS) units were incorporated into PBSu and PESu, respectively. Tstart is the temperature of first detectable deviation from the derivative curve of weight loss. Tstarts of all synthesized polyesters around 240 £jC, higher than the temperature of polycondensation reaction (220 £jC), demonstrates that there is no necessity of using a thermal stabilizer during the synthesis of these polyesters. Additionally, the thermal stability does not vary significantly with compositions in the same series polyester. Wide-angle X-ray diffractograms (WAXDs) at room temperature were obtained from polyesters crystallized isothermally at a temperature around 5-20 £jC below their melting temperatures. WAXD patterns of two series polyesters elucidated that the incorporation of PS or MPS units into PBSu markedly inhibits the crystallization behavior of PBSu. The phenomenon also occurred in PEBSu copolyesters when BS units were incorporated into PESu. Results of WAXD and DSC measurements showed that PMPSu is a amorphous polyester. The retarding effect on crystallization by methyl substituents on the polymer chain is efficient.