Cyclophilins are ubiquitous enzymes that are involved in protein folding, signal transduction, viral proliferation, oncogenesis, and regulation of the immune system. Cyclophilin A is the prototype of the cyclophilin family. We use molecular dynamics to describe the catalytic mechanism of cyclophilin A in full atomistic detail by sampling critical points along the reaction coordinate, and use accelerated molecular dynamics to sample cis-trans interconversions. At these critical points, we analyze the conformational space sampled by the active site, flexibility of the enzyme backbone, and modulation of binding interactions.We use Kramer’s rate theory to determine how diffusion and free energy contribute to lowering the activation energy of prolyl isomerization. We also find preferential binding modes of several cyclophiln A inhibitors, and compare the conformational space sampled by inhibited cyclophilin A to the conformational space sampled during wild-type interactions. We also analyze the mechanism of the next family member cyclophilin B in order to probe differences in enzyme dynamics and intermolecular interactions that could possibly be exploited in isoform-specific drug design. Our results indicate that cyclophilin proceeds by a conformational selection binding mechanism that manipulates substrate sterics, electrostatic interactions, and multiple reaction timescales in order to speed up reaction rate. Conformational space sampled by cyclophilin when inhibited and when undergoing wild-type interactions share significant similarity. Cyclophilins A and B do have notable differences in enzyme dynamics, due to variation in intramolecular interactions that arise from variation in primary structures. This work demonstrates how computational methods can be used to clarify catalytic mechanisms.

Compensating an employee for work performed or services rendered constitutes an important aspect of personnel management. The question of determining and establishing appropriate wages and salaries for comparable, different and varied jobs in an organization is one that raises complex, thorny and even nebulous issues such as "equity." The eight-week intensive training of the intern was a considerable concentration on the basic and specific methods of determining the relative ranks of jobs on the basis of their contents as judged by certain defined job characteristics or factors. In the early part of the internship program, the intern was acquainted with the basic philosophy and fundamental methods of job evaluation. The intern was subsequently introduced to the actual job evaluation methods as applied in TWA. Actual case problems and situations were studied; job descriptions were reviewed, audit of jobs were conducted; the intern had the opportunity of observing and participating in actual information collecting, verifying and recording process. The intern was acquainted with the techniques of compiling salary surveys and applying such information as a method of comparing internal salary structures with external market conditions. The latter part of the program was largely a concentration on and analysis of job descriptions and organizational structures of Ethiopian Airlines. The study basically involved the understanding of the salary structures of management personnel of Ethiopian Airlines, the investigation of the possibilities of translating TWA job evaluation methods, and the subsequent application of the methods employed by TWA to that of Ethiopian Airlines.

Syftet med denna uppsats är att utifrån ett transperspektiv förstå hur transpersoners kön och sexualitet förhålls till varandra utifrån kropp, tid och partners. Studiens material består av intervjuer med tre olika transpersoner om deras könsidentitet, sexuella läggning och transerfarenheter. Som teoretiskt ramverk står Judith Butlers Gender Trouble som exempel på queerteori, samt Jay Prossers Second Skins som exempel på transteori. Resultatet av studien är att subjekts identitet och begär står i relation till varandra samt att transpersoners antagna eller aktiva gränsöverskridanden gör att de som subjekt kan erfara denna relation med större tydlighet och över flera kategorier, med kropp, tid och partners som tydligast exempel.

Group I introns are catalytic RNAs with the ability to splice out of RNA transcripts, often without the aid of proteins. These self-splicing introns have been reengineered to create ribozymes with the ability to catalyze reactions. One such ribozyme, derived from a Pneumocystis carinii group I intron, has been engineered to sequence specifically remove a targeted segment from within an RNA substrate, which is called the trans excision-splicing reaction.The two catalytic steps of the trans excision-splicing reaction occur at positions on the substrate known as the 5' and 3' splice sites. Strict sequence requirements at these sites could potentially limit the target choices for the trans excision-splicing ribozyme, so the sixteen possible base pair combinations at the 5' splice site and the four possible nucleotides at the 3' splice site were tested for reactivity. All base pair combinations at the 5' splice site allow the first reaction step (5' hydrolysis) to occur and several combinations allow the second step to occur, resulting in trans excision-splicing product formation. Moreover, we found that non-Watson-Crick base pairs are important for 5' splice site recognition and prevent product degradation via hydrolysis at other sequence positions. The sequence requirement at the 3' splice site is absolute, as guanosine alone produced complete product.To date, the experiments with the trans excision-splicing ribozyme have been conducted in vitro. The further development of this ribozyme as a biochemical tool and as a potential therapeutic agent requires in vivo reactivity. Thus, a prokaryotic system was designed and tested to assess the catalytic potential of the trans excision-splicing ribozyme. We show that the ribozyme successfully excised a single, targeted nucleotide from a mutated green fluorescent protein transcript in Escherichia coli. On average, 12% correction was observed as measured by fluorescence and approximately 1.2% correction was confirmed through sequence analysis of isolated transcripts.We have used these studies to further characterize trans excision-splicing ribozymes in vitro and to pave the way for future development of this ribozymereaction in vivo. These results increase our understanding of this ribozyme and advance this reaction as a biochemical tool with potential therapeutic applications.

This narrative chronicles the dissemination of sacred music from the eastern seaboard to the West and South spanning a time frame from the colonial era to the latter part of the Early Nationalist Period (1700-1820). Musical culture in its migration away from the eastern seaboard also parallels the greater western and southern expansion of the United States from its initial configuration of localized regional subgroups to the beginnings of a larger national identity. From this conceptual base, sacred music becomes a vehicle for understanding not only religious and musical changes over time, but also the broader maturity of a nation. Focusing on this period allows for inquiries both into the development of hymnody in the Middle Atlantic, and the subsequent developments of the West and South. These chronological delimitations allow for a discussion of musical practice beginning with formative sacred music developments and continuing to the incorporation of techniques shaped by reform-minded musicians from the eastern seaboard. The following topics guided the construction of this thesis: explicating how the Middle Atlantic region shaped compositional trends, aesthetic, and performance practice of the American West and South; identifying the various southern cultures as understood by eighteenth and nineteenth-century southerners and their application to sacred music practice; understanding how nineteenth-century Americans distinguished between the West and the South; understanding how southern and western music relates to individual denominations and cultures within these areas; and understanding performance practice common to the evangelical and non-evangelical branches of individual sects. Identifying patterns of development in American sacred music of the South and West involves documentation of performance practice, denominational aesthetics, and tunebook bibliography. The study of eighteenth-and-nineteenth-century material by twentieth-and-twenty-first-century writers has falsely defined cultural borders of this region according to a post-bellum conceptualization of the boundaries of the North and South. Prior to 1850, writers defined their borders according to a different set of geographic boundaries than today. Consequently, this thesis differs in terms of geographic and cultural definitions of the North and South from current scholarship because of this writer’s application of colonial and Early Nationalist understandings of American culture.

Outfacing the Storm is a song cycle that tells the story of the spectacular failure-turned-triumph of the Imperial Trans-Antarctic Expedition. Led by Sir Ernest Shackleton, the Expedition was an attempt to trek overland across the whole of the Antarctic continent. Shackleton’s ship, the Endurance, launched from England in August of 1914 with twenty-eight men. Within weeks of entering the polar latitudes, ice ensnared the ship. The Endurance remained stuck fast until the spring breakup crushed its hull, and it sank in November of 1915. The crew struck out for civilization, and, after six months and over one thousand miles of travel by foot, by ice-drift, and by lifeboat, they returned home alive. The Expedition’s safe return was heavily credited by its crew to Shackleton himself. A man of intense character, burning passion, and unfailing determination, Shackleton put the needs of his crew ahead of all else. His individual dedication to each member of the voyage was an inspiration to each. Ernest Shackleton, however, was a private man. He hid his own concerns from all except those closest to him. During the Expedition, he feared for the well-being of the crew. In the largest sense, he feared failure. Shackleton was only ever content while at sea. “Sometimes,” he wrote to his wife, “I think I am no good at anything but being away in the wilds… I grow restless and feel any part of youth is slipping away from me and that nothing matters… I feel I am no use to anyone unless I am outfacing the storm in wild lands.” This song cycle tells the tale of the Expedition through Shackleton’s eyes. The cycle is in eleven movements—nine recounting the story, plus a prologue and epilogue. All of the text is Shackleton’s own. The nine middle movements are taken from Shackleton’s memoir about the voyage, South. The prologue and epilogue are taken, respectively, from an interview and the above letter. / Music, Butler School of / text

This paper analyzes the nature of linguistic interactions between host communities and international tourists. The tourism-based context provides an excellent platform from which to describe the sociolinguistic influences that American tourists have had on Mexican communities. Specifically, the language use of local vendors in Puerto Peñasco/Rocky Point, Mexico, is described in terms of the various linguistic characteristics that constitute their particular dialect of English. Not only does this work emphasize the sociocultural foundation of language acquisition, it also illustrates the type of language that is learned in economically motivated situations. The results also emphasize how the growing ubiquity of (American) English in tourism contexts establishes distinct attitudes towards the United States and those who live there.

2 pp. / [Healthy Fats -- Guide for Improving the Quality of Fat Intake] / The fact sheet reviews healthy fats and how to incorporate a healthy amount of fat into our diet. Fats are necessary for our bodies to function properly. In fact, fats are an important part of a healthy diet and we can't live without them. Fats can be grouped into two groups: saturated and unsaturated. Unsaturated fats include polyunsaturated and monounsaturated fats. Both these fats, when eaten in moderation and used in place of saturated and trans fats, can help lower cholesterol levels and decrease the risk of heart disease. We provide a list of "Do's" and "Tips" which gives examples of how to select fats wisely and incorporate healthy changes into our diet. We also provide a guide for selecting an appropriate portion size of fat.

2 pp. / The fact sheet reviews healthy fats and how to incorporate a healthy amount of fat into our diet. Fats are necessary for our bodies to function properly. In fact, fats are an important part of a healthy diet and we can't live without them. Fats can be grouped into two groups: saturated and unsaturated. Unsaturated fats include polyunsaturated and monounsaturated fats. Both these fats, when eaten in moderation and used in place of saturated and trans fats, can help lower cholesterol levels and decrease the risk of heart disease. We provide a list of "Do's" and "Tips" which gives examples of how to select fats wisely and incorporate healthy changes into our diet. We also provide a guide for selecting an appropriate portion size of fat.

Reflecting the masculine ethos of the larger comic book industry, superhero comics continue to be male-dominated spaces. Within comic studies, superhero scholars problematically normalize this androcentrism by reiterating the genre’s masculinist rhetoric, repeatedly positioning superheroes as stoic figures of whiteness, nationhood, heteronormativity and able-bodied masculinity. Although some intervention has been made to challenge these interpretations, scholars fail to acknowledge how transgender and/or transsexual readers evaluate comic heroes. This thesis provides one such intervention into the field, specifically focusing on the last son of Krypton, Superman. Drawing together the work of trans, queer, feminist, psychoanalytic, and monster theorists, my research attempts to “trans” Superman; thus, (re)reading the Man of Steel in a way that distinctly reflects the experiences of those who are denied access to the figure via their/our own gender “transgressions”. By interpolating transsexuality into the Superman narrative, I rewrite the figure’s place within the genre’s cis-sexist, masculinist history and while doing so, (re)position him as a more suitable hero for the trans community. / Thesis (Master, Gender Studies) -- Queen's University, 2013-12-05 10:35:05.511