Synthesis of fluorescent analogues of a-tocopherol as ligands for the human a-tocopherol transfer protein (a-TTP) /

To further understand in vivo localization and trafficking of a-tocopherol (a-Toe), the most biologically active form of vitamin E, between lipid environments, tocopherols are required that can be followed by teclu1iques such as confocal microscopy and fluorescence resonance energy transfer (FRET) assays. To this end, sixteen fluorescent analogues of a-tocopherol (la-d [(1)anthroy loxy -a-tocopherols, A O-a-Toes], 2a-d [w-nitro benzoxadiazole-a-tocopherols, NBD-aToes], 3a-d [w-dansyl-a-tocopherols, DAN-a-Toes], and 4a-d [w-N-methylanthranilamide-atocopherols, NMA-a-TocsD were prepared by substituting fluorescent labels at the terminus of w-functionalized alkyl chains extending from C-2 of the chroman ring while retaining key binding features of the natural ligand. These compounds were prepared starting from (S)-Trolox® acid VIa esterification, protection, and reduction producing the silyl-protected (S)-Trolox aldehyde that was coupled using Wittig chemistry to different w-hydroxyalkylphosphonium bromides. Reduction of the alkene generated the w-hydroxy functionalized 2-n-alkyl intermediates 9a-d having the necessary 2R stereochemistry. A series of functional group manipulations including mesylation, substitution with azide, and hydride reduction provided w-amino functionalized intermediates 12a-d as well. Coupling intermediates 9a-d and 12a-d with the selected fluorophores (9- anthracene carboxylic acid, 4-chloro-7-nitrobenz-2-oxa-l,3-diazole, 5- dimethylaminonapthalene-l-sulfonyl chloride, and I-methyl-2H-3,1-benzoxazine-2,4(1H)dione), followed by deprotection of the phenolic silyl group, gave the desired fluorescent ligands la-d, 2a-d, 3a-d and 4a-d in good yield. Assessment of their binding affinities with recombinant human a-tocopherol transfer protein (ha-TTP) utilizing fluorescent titration binding assays identified competent ligands for further use in protein studies. Compounds Id (C9-AO-a-Toc) and 2d (C9-NBD-a-Toc) both having nonyl alkyl chain extensions between the chromanol and fluorophore were shown to bind specifically to ha-TTP with dissociation constants (KdS) of approximately 280 nM and 55 nM respectively, as compared to 25 nM for the natural ligand 2R,4'R,^'R-a-tocophQxoL.

Synthesis of isotope-labelled methoxypyrazine compounds as internal standards and quantitative determination of aroma methoxypyrazines in water and wines by solid-phase extraction with isotope dilution-GC-MS /

An efficient way of synthesizing the deuterium labelled analogues of three methoxypyrazine compounds: 2-d3-methoxy-3-isopropylpyrazine, 2-d3-methoxy-3- isobutylpyrazine, and 2-d3-methoxy-3-secbutylpyrazine, has been developed. To confirm that the deuterium labels had been incorporated into the expected positions in the molecules synthesized, the relevant characterization by NMR, HRMS and GC/MS analysis was conducted. Another part of this work involved quantitative determination of methoxypyrazines in water and wines. Solid-phase extraction (SPE) proved to be a suitable means for the sample separation and concentration prior to GC/MS analysis.Such factors as the presence of ethanol, salt, and acid have been investigated which can influence the recovery by SPE for the pyrazines from the water matrix. Significantly, in this work comparatively simple fractional distillation was attempted to replace the conventional steam distillation for pre-concentrating a sample with a relatively large volume prior to SPE. Finally, a real wine sample spiked with the relevant isotope-labelled methoxypyrazines was quantitatively analyzed, revealing that the wine with 10 beetles per litre contained 138 ppt of 2-methoxy-3-isopropylpyrazine. Interestingly, we have also found that 2-methoxy-3-secbutylpyrazine exhibits an extremely low detection limit in GC/MS analysis compared with the detection limit of the other two methoxypyrazines: 2- methoxy-3-isopropylpyrazine and 2-methoxy-3-isobutylpyrazine.

The metacognitive cue of fluency on taste perception

The relative ease tha t a person experiences while performing cognitive operations, namely processing fluency, affects a broad range of judgments such as product evaluations. For example, an increase in fluency through repeated exposure to product packages enhances attitude toward the brand (Janiszewski 1993). This thesis examined the effect of fluency on taste perception and demonstrated where the fluency created an advantage or disfluency created a disadvantage for taste evaluations. Experiment 1 examined the effect of perceptual fluency on taste perception. It was found that perceptual disfluency derived from r eading the labels (i.e., font) lowered taste evaluations only when it was experienced be for the sensory experience. Experiment 2 examined the effect of linguistic fluency (i.e., pronunciation) on taste perception. However there was no evidence for the effect of linguistic fluency on taste perception. Thus, it is concluded that either the effect size of linguistic fluency is lower than perceptual fluency, or participants discounted their linguistic fluency experience because they realized that the brand names used in Experiment 2 were not real brand names. To sum up, it was found that perceptual disfluency created by presenting a difficult to read product-related information created a disadvantage for taste perception compared to when no information was presented. Therefore, this thesis provides the first evidence for the effect of the metacognitive cue of fluency on sensory evaluations.

Nietzsche's children : a physiological analysis of the scholar's task

Throughout Nietzsche's writings we find discussions of the proper relationship of the scholar/scientist to the philosopher, wi th the scholar of ten being presented in a derogatory light. In this thesis, I examine Nietzsche's por t rai t of the scholar through the lens of his physiological or clinical perspective as articulated by Dr. Daniel R. Ahern in his monograph entitled Nietzsche as Cultural Physician. My aim in doing so is to grasp the affirmative, creative aspect of this seemingly destructive polemic against scholars. I begin wi th a detailed discussion of Nietzsche's por t rai t of the scholar in Beyond Good and Evil. This includes an explication of Ahern's position, followed by an application of the diagnostic perspective to Nietzsche's discussion of the objective type, the skeptic, and the critic. I then look at how the characteristics of all three types are present in the Nietzschean 'free spirit.' I also discuss the physiological basis of esotericism in Nietzsche's work, as well as Nietzsche's revaluation of the scholarly vi r tue known as Red/ichkeit (or 'honesty'). I conclude wi th comments on the free spirit's relationship to the future.

Canadian Niagara Power Glass Slide - Engineer Drawing (untitled)

Engineer drawing (untitled), some of the labels read "exciter chamber", "fore bay", "power house floor".

Inniskillin fonds, 1970-2014, n.d.

Inniskillin Wines was founded by Karl Kaiser and Donald Ziraldo in 1975 in Niagara-on-the-Lake, Ontario. They had met the previous year, when Karl Kaiser, a winemaker and chemist, purchased some grapes from Donald Ziraldo, who owned and operated Ziraldo Nurseries. The two shared a vision of producing better quality Canadian wines and formed a partnership, with Kaiser making the wine and Ziraldo serving as company President. In 1975, they were granted a winery license by the LCBO, the first one granted since 1929. The company name Inniskillin was derived from the Inniskilling Fusilliers, an Irish regiment whose Colonel once owned the land that Ziraldo Nurseries occupied. This was the original site of the winery, although in 1978 the winery moved to the Brae Burn Estate, their current location. In 1982 the winery expanded by 50 acres with the addition of the Montague Vineyard, and another 50 acres was acquired in 1991. The Niagara-on-the-Lake vineyard produces single vineyards bottlings of Chardonnay, Pinot Noir, Merlot and Pinot Grigio/Pinot Gris. In 1984, Karl Kaiser began producing icewine from Vidal grapes frozen naturally on the vine. Inniskillin garnered international acclaim for the quality of their icewines, receiving the prestigious Grand Prix d’Honneur at VinExpo in 1991, for their 1989 Vidal icewine. This established Inniskillin as a producer of world class wines, while also raising the profile of Canadian wines in general. The company branched out their operations, first acquiring vineyards in the Napa Valley in 1989 to form Inniskillin Napa (producing wines under the Terra label), and in 1994 establishing Inniskillin Okanagan in the Okanagan Valley in British Columbia. The Napa valley venture ceased in the mid 90’s, while Inniskillin Okanagan continues to operate. In 2006, Karl Kaiser and Donald Ziraldo left Inniskillin. Kaiser retired, while Ziraldo became chair of the Vineland Research and Innovation Center (2006-2011), and remains involved in the wine industry. In 2007, Bruce Nicholson joined Inniskillin as winemaker. Nicholson continues to produce award-winning wines under the Inniskillin label, receiving the top award, the Premio Speciale Gran Award, at Vinitaly 2009 for his 2006 Gold Vidal and his 2006 Sparkling Vidal Icewine. In 2012, he received several awards for the 2008 Riesling Icewine, including gold at the International Wine and Spirits Competition in London, UK, the San Francisco International Wine Championships, and Selections Mondials des Vins Canada.

Seagram Museum Collection

The Seagram Museum was opened on May 16th, 1984 by the Honourable William G. Davis, Premier of Ontario. The museum was devoted to the history and technology of the wine and spirit industry. The museum focused on wine-making and distillation, as well as barrel-making and cork manufacturing. The museum was located adjacent to the Seagram Distillery in Waterloo, Ontario. In 1997, the museum closed due to lack of funds.

Letter - Lyle Vanclief, M.P. to Donald Ziraldo, 1996

A letter from Lyle Vanclief, M.P. Prince Edward- Hastings, to Donald Ziraldo in regards to Bill C222. The Bill would require warning labels on alcoholic beverages in order to encourage moderation. The letter indicates that Mr. Ziraldo has sent a letter to said Vanclief with concern about the Bill. Vanclief responds in this letter by indicating his disapproval for Bill C222.

The Impact of Labeling in Childhood on the Sense of Self of Young Adults

Research studies on labeling of children have either focused on the effects of formal labels on the lives of children with exceptionalities and mental health issues, or the effect of informal labeling by parents, peers and teachers on teenagers. The effects of informal labeling in childhood and its implications in later life or for one’s career choice have not yet been examined. This study adds to the growing research on informal labeling. The purpose of this qualitative study was to determine what negative effects informal labeling of children as deviant had on their lives. Data were gathered through semi-structured interviews conducted with seventeen young adults, between the ages of sixteen and thirty years, from a post-secondary institution and an organization for homeless youth. The results showed an initial negative impact on the lives of the young adults during their childhood and early teenage years but as they progressed into their late teens and early adulthood, most were able to overcome their negative labels suggesting resilience. There were no significant gender differences in the impact of the labels. The implications of the study for policy makers and parents are discussed as well as some recommendations for parents and practitioners are offered.

Feature Selection and Classification Using Age Layered Population Structure Genetic Programming

The curse of dimensionality is a major problem in the fields of machine learning, data mining and knowledge discovery. Exhaustive search for the most optimal subset of relevant features from a high dimensional dataset is NP hard. Sub–optimal population based stochastic algorithms such as GP and GA are good choices for searching through large search spaces, and are usually more feasible than exhaustive and deterministic search algorithms. On the other hand, population based stochastic algorithms often suffer from premature convergence on mediocre sub–optimal solutions. The Age Layered Population Structure (ALPS) is a novel metaheuristic for overcoming the problem of premature convergence in evolutionary algorithms, and for improving search in the fitness landscape. The ALPS paradigm uses an age–measure to control breeding and competition between individuals in the population. This thesis uses a modification of the ALPS GP strategy called Feature Selection ALPS (FSALPS) for feature subset selection and classification of varied supervised learning tasks. FSALPS uses a novel frequency count system to rank features in the GP population based on evolved feature frequencies. The ranked features are translated into probabilities, which are used to control evolutionary processes such as terminal–symbol selection for the construction of GP trees/sub-trees. The FSALPS metaheuristic continuously refines the feature subset selection process whiles simultaneously evolving efficient classifiers through a non–converging evolutionary process that favors selection of features with high discrimination of class labels. We investigated and compared the performance of canonical GP, ALPS and FSALPS on high–dimensional benchmark classification datasets, including a hyperspectral image. Using Tukey’s HSD ANOVA test at a 95% confidence interval, ALPS and FSALPS dominated canonical GP in evolving smaller but efficient trees with less bloat expressions. FSALPS significantly outperformed canonical GP and ALPS and some reported feature selection strategies in related literature on dimensionality reduction.

Feature Selection and Classification Using Age Layered Population Structure Genetic Programming

The curse of dimensionality is a major problem in the fields of machine learning, data mining and knowledge discovery. Exhaustive search for the most optimal subset of relevant features from a high dimensional dataset is NP hard. Sub–optimal population based stochastic algorithms such as GP and GA are good choices for searching through large search spaces, and are usually more feasible than exhaustive and determinis- tic search algorithms. On the other hand, population based stochastic algorithms often suffer from premature convergence on mediocre sub–optimal solutions. The Age Layered Population Structure (ALPS) is a novel meta–heuristic for overcoming the problem of premature convergence in evolutionary algorithms, and for improving search in the fitness landscape. The ALPS paradigm uses an age–measure to control breeding and competition between individuals in the population. This thesis uses a modification of the ALPS GP strategy called Feature Selection ALPS (FSALPS) for feature subset selection and classification of varied supervised learning tasks. FSALPS uses a novel frequency count system to rank features in the GP population based on evolved feature frequencies. The ranked features are translated into probabilities, which are used to control evolutionary processes such as terminal–symbol selection for the construction of GP trees/sub-trees. The FSALPS meta–heuristic continuously refines the feature subset selection process whiles simultaneously evolving efficient classifiers through a non–converging evolutionary process that favors selection of features with high discrimination of class labels. We investigated and compared the performance of canonical GP, ALPS and FSALPS on high–dimensional benchmark classification datasets, including a hyperspectral image. Using Tukey’s HSD ANOVA test at a 95% confidence interval, ALPS and FSALPS dominated canonical GP in evolving smaller but efficient trees with less bloat expressions. FSALPS significantly outperformed canonical GP and ALPS and some reported feature selection strategies in related literature on dimensionality reduction.

Public Decisions: Solidarity and the Status Quo

A public decision model specifies a fixed set of alternatives A, a variable population, and a fixed set of admissible preferences over A, common to all agents. We study the implications, for any social choice function, of the principle of solidarity, in the class of all such models. The principle says that when the environment changes, all agents not responsible for the change should all be affected in the same direction: either all weakly win, or all weakly lose. We consider two formulations of this principle: population-monotonicity (Thomson, 1983); and replacement-domination (Moulin, 1987). Under weak additional requirements, but regardless of the domain of preferences considered, each of the two conditions implies (i) coalition-strategy-proofness; (ii) that the choice only depends on the set of preferences that are present in the society and not on the labels of agents, nor on the number of agents having a particular preference; (iii) that there exists a status quo point, i.e. an alternative always weakly Pareto-dominated by the alternative selected by the rule. We also prove that replacement-domination is generally at least as strong as population-monotonicity.

Federal Constitutionalism and Aboriginal Difference

The author outlines a new legal approach, which he labels federal constitutionalism, to the question of aboriginal difference in Canada. This approach has the potential to open up more fruitful avenues for the resolution of aboriginal law issues than either the “frozen rights” approach currently adopted by the Supreme Court of Canada or the treaty federalism approach, which posits that treaties should be used to resolve all differences between aboriginals and non-aboriginals. The author outlines the difficulties inherent in both the frozen rights and treaty federalism approaches. Federal constitutionalism, in contrast, draws its vitality from an organic understanding of Canada’s constitutional experience. It would allow aboriginal peoples to be seen as federal actors who have historically shaped the Canadian federation. Federal constitutionalism is a multi-faceted approach that would permit aboriginal questions to be addressed using the federal principle, thereby allowing the legal focus to move away from section 35 of the Constitution Act, 1982. Aboriginal peoples would be able to exercise the rights of sovereignty over their own internal affairs, while individual aboriginals could participate directly in federal and provincial governments without having to proceed through the intermediary of aboriginal representatives. Federal constitutionalism would allow aboriginal peoples a guaranteed sphere of autonomy, while permitting recognition of their historical interdependence with non-aboriginal peoples.

La protection des données personnelles en France

Un résumé en anglais est également disponible.