Thesis (Ph. D.)--University of Sydney, 2009. / Includes graphs and tables. Title from title screen (viewed November 06, 2009). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Engineering and Information Technologies. Degree awarded 2009; thesis submitted 2008. Includes bibliographical references. Also available in print form.

Thesis (Ph. D.)--University of Rochester. Dept. of Chemistry. / Bibliography: leaves 86-88.

Thesis (Ph.D.)--University of Delaware, 2009. / Principal faculty advisors: Mark A. Barteau and Jochen A. Lauterbach, Dept. of Chemical Engineering.. Includes bibliographical references.

published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

Poly(ethylene oxide) (PEO) is known for facilitating the electrospinning of biopolymer solutions, that are otherwise not electrospinnable. The objective of this study was to investigate the mechanism by which PEO enables the formation of whey protein isolate (WPI) electrospun fibers under different pH conditions. This investigation revealed that the addition of PEO increased the viscosity of WPI/PEO (10% w/w WPI; 0.4% w/w PEO) solutions. Difference in pH levels of the polymer solutions affected electrospinnability and fiber morphology. Acidic solutions resulted in smooth fibers (700 ± 105 nm) while neutral solutions produced spheres (2.0 ± 1.0 um) linked with ultrafine fibers (138 ± 32 nm). In comparison, alkaline solutions produced fibers (191 ± 38 nm) that were embedded with spindle-like beads (1.0 ± 0.5 um). Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analyses revealed that the native globular configuration of WPI was not altered under neutral conditions. By contrast, the electrophoresis and spectrometry data indicated that WPI was denatured and hydrolyzed under acidic conditions, which facilitated the formation of smooth fibers. C13 nuclear magnetic resonance (NMR) and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopies showed that the increase random coil and a-helix secondary structures in WPI contributed to the formation of bead-less electrospun fibers. Also, C13 NMR analysis showed no evidence of chemical interaction between WPI and PEO. Scanning transmission electron microscopy coupled with energy dispersive X-rays (STEM-EDAX) revealed that WPI was uniformly distributed within WPI/PEO electrospun fibers. Observations by scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM) indicated that fibers possessed a solid core. All these findings suggested that PEO enables the formation of WPI/PEO electrospun fibers by entanglement/entrapment/deposition. Preliminary studies were conducted on hydroxypropyl methyl cellulose (HPMC). In the absence of PEO, HPMC enabled the formation of WPI electrospun fibers under acidic conditions (124 ± 46 nm). FTIR analyses indicated that there was no interaction between HPMC and WPI, suggesting that HPMC aided in the electrospinning of WPI fibers, also by entanglement/entrapment/deposition. Hence, HPMC and PEO aid in the electrospinning of WPI fibers by entanglement/entrapment/deposition, which can be manipulated by alterations in the protein configuration and solution properties. / Natural Sciences and Engineering Research Council (NSERC) of Canada and the Dairy Farmers of Ontario (DFO)

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 185-187) Also available in print.

Copolymer-cobalt complexes have been formed by thermolysis of dicobalt octacarbonyl in solutions of copolysiloxanes. The copolysiloxane-cobalt complexes formed from toluene solutions of PDMS-b-[PMVS-co-PMTMS] block copolymers were annealed at 600-700 °C under nitrogen to form protective siliceous shells around the nanoparticles. Magnetic measurements after aging for several months in both air and in water suggest that the ceramic coatings do protect the cobalt against oxidation. However, after mechanical grinding, oxidation occurs. The specific saturation magnetization of the siliceous-cobalt nanoparticles increased substantially as a function of annealing temperature, and they have high magnetic moments for particles of this size of 60 emu g⁻¹ Co after heat-treatment at temperatures above 600 °C. The siliceous-cobalt nanoparticles can be re-functionalized with aminopropyltrimethoxysilane by condensing the coupling agent onto the nanoparticle surfaces in anhydrous, refluxing toluene. The concentration of primary amine obtained on the surfaces is in reasonable agreement with the charged concentrations. The surface amine groups can initiate L-lactide and the biodegradable polymer, poly(L-lactide), can be polymerized directly from the surface. The protected cobalt surface can also be re-functionalized with poly(dimethylsiloxane) and poly(ethylene oxide-co-propylene oxide) providing increased versatility for reacting polymers and functional groups onto the siliceous-cobalt nanoparticles.Phthalonitrile containing graft copolysiloxanes were synthesized and investigated as enhanced oxygen impermeable shell precursors for cobalt nanoparticles. The siloxane provided a silica precursor whereas the phthalonitrile provided a graphitic precursor. After pyrolysis, the surfaces were silicon rich and the complexes exhibited a substantial increase in Ms. Early aging data suggests that these complexes are oxidatively stable in air after mechanical grinding. Aqueous dispersions of macromolecule-magnetite complexes are desirable for biomedical applications. A series of vinylsilylpropanol initiators, where the vinyl groups vary from one to three, were prepared and utilized for the synthesis of heterobifunctional poly(ethylene oxide) oligomers with a free hydroxy group on one end and one to three vinylsilyl groups on the other end. The oligomers were further modified with carboxylic acids via ene-thiol addition reactions while preserving the hydroxyl functionality at the opposite terminus. The resulting carboxylic acid heterobifunctional PEO are currently being investigated as possible dispersion stabilizers for magnetite in aqueous media. / Ph. D.

A report that the ethylene oxide fumigation of animal diets reduced their nutritive value has prompted a more detailed study of the reactions of this commercially-used fumigant. It has been demonstrated that the 24-hour fumigation of commercial casein, egg albumin and lactalbumin with ethylene oxide greatly reduced the ability of these proteins to support the growth of weanling rats when the proteins were fed as 9% of a purified diet as the sole source of amino acid nitrogen. Thorough drying of the proteins reduced the extent of subsequent fumigation damage. The nutritional quality of the three proteins was completely restored by the supplementary feeding of L-histidine-HCl, DL-methionine, and L-lysine-HCl, or, in some cases, only one or two of these amino acids. Microbiological assay confirmed a reduction in the biological availability of 11% to 83% of the histidine, 6% to 55% of the methionine and 51 to 92% of the lysine, depending on the protein and the amount of moisture present during fumigation. Histidine was generally the most labile amino acid and lysine the least labile. Additional amino acids appeared to be affected when an hydrolysate of casein was fumigated. The ethylene oxide fumigation of soybean alpha protein improves its growth-promoting quality for the rat. Evidence is presented that fumigation inactivates the heat-labile proteinaceous growth inhibitor, long recognized as a component of soybean protein. Chemical justification for the destructive action of ethylene oxide on the biological value of histidine, methionine, and certain B-vitamins was sought by reacting model compounds in aqueous solution with the fumigant and identifying the products. At 25°C. and atmospheric pressure ethylene oxide readily hydroxyethylates tertiary as well as primary and secondary amine nitrogen and also the sulfur of thioethers. Imidazole and histidine yield the 1,3-bis-(2-hydroxyethyl)imidazolium derivatives; nicotinamide, nicotinic acid, and pyridine yield the corresponding N-(2-hydroxyethyl)pyridinium compounds; and N-acetylmethionine is converted to s-(2-hydroxyethyl)-N-acetylmethionine, thetin. The reaction of ethylene oxide with amino acids results in hydroxyethylation of the primary amino groups but no esterification of carboxyl groups was observed. The extent of ethylene oxide-imidazole reaction in fumigated proteins could be determined colorimetrically. In the presence of ethylene oxide the mercapto group of cysteine appears to become doubly alkylated to produce a sulfonium compound which causes a flaccid paralysis, respiratory failure and death when injected subcutaneously into weanling rats. The structure of the compound bears certain similarities to other synthetic spasmolytics. Evidence is presented that the reaction of ethylene oxide with pyridoxine, riboflavin and folic acid involves the hydroxyethylation of tertiary heterocyclic nitrogens. A striking resemblance was observed between the alkylating capacity of ethylene oxide and the sulfur and nitrogen mustards. New compounds described are 1,3-bis-(2-hydroxyethyl)imidazolium chloride; N¹-(2-hydroxyethyl)nicotinic acid, betaine; and N-(2-hydroxyethyl) nicotinic acid chloride. N-(2-hydroxyethyl)nicotinamide chloride was also crystallized and its melting point found to be 14 degrees centigrade higher than previously reported in the literature. Other reaction products were studied in solution or as solid adducts of reinecke's salt or phosphotungstic acid. The proteolytic activity of chymotrypsin was progressively reduced by exposure of the cystalline enzyme to ethylene oxide vapor or by treatment of the enzyme in aqueous solution with the fumigant. However, treatment of chymotrypsin in aqueous solution with ethylene oxide did not impair its ability to hydrolyze p-nitrophenyl acetate. Likewise, the imidazole groups of native chymotrypsin appear to be protected from the hydroxyethylating action of ethylene oxide. Denaturing the protein in 8 M urea uncovered the imidazole groups and permitted reaction with the fumigant. On the basis of these studies it is felt that the effect of existing commercial ethylene oxide fumigating processes on the nutritive value of foods and feedstuffs bears closer investigation. / Ph. D.

Faculty of health sciences School of Public Health 0204521g dgresie@yahoo.co.uk;dgresie@hotmail.com / Ethylene oxide is used widely in hospitals as a gaseous sterilant for heat-sensitive medical items, surgical instruments and other objects and fluids that come into contact with biological tissues. Although ethylene oxide is recognised as a reproductive toxicant in humans, so far few studies have been carried out to investigate the association between exposure to ethylene oxide and the occurrence of adverse reproductive outcomes (Hemminki et al 1982 and 1983; Rowland et al, 1996; Yakubova et al, 1976). The results of these studies suggested that ethylene oxide is capable of causing reproductive dysfunction and that further research is needed in order to understand its effects on reproductive health. This study investigated the association between exposure to ethylene oxide during pregnancy and adverse reproductive outcome in women sterilising staff working in sterilising units using ethylene oxide in Gauteng province, South Africa. The study had the following objectives: 1) to describe the extent and nature of ethylene oxide use in sterilising units operational in medical facilities in Gauteng; 2) to assess the current exposure to ethylene oxide in sterilising units in Gauteng; 3) to collect information on the last recognised pregnancy using a questionnaire; 4) to assess the validity of the information on the evolution and outcome of the last recognised pregnancy collected by the means of the questionnaire; 5) to assess the association between occupational exposure to ethylene oxide during pregnancy and adverse reproductive outcome. The study population was represented by singleton pregnancies that: 1) occurred in women currently working in sterilising units using ethylene oxide in Gauteng province, South Africa; 2) were the last recognised pregnancy occurring in these women after the 1st January 1992; 3) occurred while the mother was employed. The adverse reproductive outcome was defined as the occurrence of any the following: spontaneous abortion, still birth, pregnancy loss (spontaneous abortion or still birth), low birth weight and combined adverse reproductive outcome (spontaneous abortion, still birth or low birth weight). The study enrolled 68.8% of the medical facilities in Gauteng that were using ethylene oxide to sterilise medical equipment. The majority of the employees working in the sterilising units included in the study were women (96.6%) and they were employed in one of the following jobs: technician (operator), instrument packer and cleaner. xiii Most of the sterilising units participating in the study used ethylene oxide sterilisation daily and only 15.4% of them reported that the employees operating the ethylene oxide steriliser used protective clothing. Recorded levels of ethylene oxide were provided by 46.2% of the sterilising units; they were all bellow 0.25 ppm (the South African long-term exposure limit for occupational exposure to ethylene oxide is 5 ppm). Changes in ethylene oxide sterilisation equipment and or technology were reported by 42.3% of the sterilising units and they were all engineering control measures aimed at reducing exposure to ethylene oxide. Measurements of the current levels of ethylene oxide were performed at the time of the study by the National Institute for Occupational Health using hydrobromic acid-coated petroleum charcoal tubes connected to calibrated Gilian pumps through which air containing ethylene oxide was drawn. The samples were analysed by the Analytical Services of the National Institute for Occupational Health. A total of 418 samples were collected (100 blank samples, 97 personal samples and 221 static samples). Quality control was ensured by the following methods: 1) verification by an Approved Inspection Authority; 2) collection of duplicate samples; 3) collection of blank samples. These measurements showed that exposure to ethylene oxide still occurred in sterilising units (ethylene oxide was detected in 9 out of the 10 public hospitals) and that the employees most exposed are the ones working with the ethylene oxide steriliser (technician or operator). There were 113 women working in the sterilising units enrolled in the study who had been pregnant after the 1st January 1992; 109 of them agreed to participate in the study and to complete the questionnaire. Information on exposure to ethylene oxide during pregnancy was obtained from three sources: walk-through survey, questionnaire-collected data and measurements of the levels of ethylene oxide in sterilising units at the time of the study. Information on the evolution and outcome of these pregnancies was gathered from the mother using a questionnaire. The questionnaire collected demographic data, reproductive history, medical data, risk factors for the adverse reproductive outcome (environmental and occupational exposures, lifestyle), and data regarding the evolution and outcome of the last recognised pregnancy. The questionnaire also collected detailed information on the job held at the time of the last recognised pregnancy (if the woman was working with ethylene oxide, she was asked to provide a complete list of daily tasks she was performing). Prior to administration, the questionnaire was tested on a small sample of working women. xiv The validity of the questionnaire-collected information on the evolution and outcome of the last recognised pregnancy was assessed by comparing this information against medical records (considered the “gold standard”). The assessment showed that mothers’ recall was accurate for the following variables: medical facility were the pregnancy was recorded, date of the reproductive event, gestation length, vital status of the newborn, number of foetuses, child gender, disease/medical problems during pregnancy and treatment received during pregnancy. There was an error in the mothers’ reporting of the birth weight of their babies. The possible misclassification of outcome resulting from this error was shown to be nondifferential (the proportion of subjects misclassified on outcome did not depend on exposure). Therefore, this misclassification could bias the effect estimate towards the null value or it could not produce any bias at all. The analysis carried out to detect possible associations between exposure to ethylene oxide and adverse reproductive outcomes included 98 of the initial 109 pregnancies on which information had been collected (11 pregnancies were excluded from the analysis for the following reasons: 2 were multiple pregnancies, 4 were conceived before 1st January 1992 and 5 were conceived while the mother was not employed). Amongst the 98 singleton pregnancies included in the analysis, 19 were classified as exposed and 79 as unexposed to ethylene oxide. The relative risk for spontaneous abortion was RR=16.63 (95%CI=1.97-140.42; p=0.004), for stillbirths RR=3.47 (95%CI=0.63-19.01; p=0.18), for pregnancy loss RR=6.24 (95%CI=1.95- 19.93; p=0.003), for low birth weight RR=0.61 (95%CI=0.09-4.30; p=0.51) and for combined adverse reproductive outcome RR=2.09 (95%CI=1.00-4.36; p=0.06). No confounders were detected for any of the associations between exposure to ethylene oxide and the adverse reproductive outcomes under study. For the association between exposure to ethylene oxide and combined adverse reproductive outcome the analysis detected three effect modifiers: paternal age (father aged 40 or older at conception), passive smoking and maternal age (mother aged 35 or older at conception). In conclusion, this study, the first in South Africa on ethylene oxide exposure and adverse reproductive outcomes, confirmed the widespread use of ethylene oxide, exposure to this agent in public sector hospitals and associations between exposure to ethylene oxide and spontaneous abortion and between exposure to ethylene oxide and pregnancy loss (either spontaneous abortion or stillbirth). xv Moreover, the study provided data on reproductive outcomes in employed women (on which scant data are available in South Africa) and added information on the validity of selfreported pregnancy data relative to medical records. The findings of the study support the conclusions of the previous studies that had suggested that exposure to ethylene oxide during pregnancy could lead to adverse reproductive outcomes. The study detected no associations between exposure to ethylene oxide and stillbirth, low birth weight or between exposure to ethylene oxide and combined adverse reproductive outcome.

In this study, two new Multi-Objective Optimization (MOO) techniques are developed. The two new techniques, the Objective-Based Gradient Algorithm (OBGA) and the Principal Component Grid Algorithm (PCGA), were developed with the goals of improving the accuracy and efficiency of the Pareto domain approximation relative to current MOO techniques. Both methods were compared to current MOO techniques using several test problems. It was found that both the OBGA and PCGA systematically produced a more accurate Pareto domain than current MOO techniques used for comparison, for all problems studied. The OBGA requires less computation time than the current MOO methods for relatively simple problems whereas for more complex objective functions, the computation time was larger. On the other hand, the efficiency of the PCGA was higher than the current MOO techniques for all problems tested. The new techniques were also applied to complex chemical engineering problems. The OBGA was applied to an industrial reactor producing ethylene oxide from ethylene. The optimization varied four of the reactor input parameters, and the selectivity, productivity and a safety factor related to the presence of oxygen in the reactor were maximized. From the optimization results, recommendations were made based on the ideal reactor operating conditions, and the control of key reactor parameters. The PCGA was applied to a PI controller model to develop new tuning methods based on the Pareto domain. The developed controller tuning methods were compared to several previously developed controller correlations. It was found that all previously developed controller correlations showed equal or worse performance than that based on the Pareto domain. The tuning methods were applied to a fourth order process and a process with a disturbance, and demonstrated excellent performance.