Semiempirical Study of the Bergman Reaction: Towards a Computationally Efficient and Accurate Method for Modeling Enediyne Anticancer Antibiotics

Over the past 7 years, the enediyne anticancer antibiotics have been widely studied due to their DNA cleaving ability. The focus of these antibiotics, represented by kedarcidin chromophore, neocarzinostatin chromophore, calicheamicin, esperamicin A, and dynemicin A, is on the enediyne moiety contained within each of these antibiotics. In its inactive form, the moiety is benign to its environment. Upon suitable activation, the system undergoes a Bergman cycloaromatization proceeding through a 1,4-dehydrobenzene diradical intermediate. It is this diradical intermediate that is thought to cleave double-stranded dna through hydrogen atom abstraction. Semiempirical, semiempiricalci, Hartree–Fock ab initio, and mp2 electron correlation methods have been used to investigate the inactive hex-3-ene-1,5-diyne reactant, the 1,4-dehydrobenzene diradical, and a transition state structure of the Bergman reaction. Geometries calculated with different basis sets and by semiempirical methods have been used for single-point calculations using electron correlation methods. These results are compared with the best experimental and theoretical results reported in the literature. Implications of these results for computational studies of the enediyne anticancer antibiotics are discussed.

Marx and the Bible: José Miranda’s Critique of the Philosophy of Oppression

This paper critically examines the liberation theology of José Porfirio Miranda, as expressed in his Marx and the Bible (1971), with a focus on the central idea (and subtitle) of this work: the “Critique of the Philosophy of Oppression.” Miranda’s critique is examined via certain key tropes such as “power,” “justice,” and “freedom,” both in the context of late twentieth-century Latin American society, and in the state of the “post-Christian” and “post-Marxist” world more generally, vis-à-vis contemporary liberal justice theory. Close examination of the potentialities, paradoxes and subtle evasions in Miranda’s critique leads not to the conclusion that Miranda does not go far enough in his application of Christian principles to justice theory.

ARISTOTLE AND THE IMPORTANCE OF VIRTUE IN THE CONTEXT OF THE POLITICS AND THE NICOMACHEAN ETHICS AND ITS RELATION TO TODAY

While much of Aristotle's works are preserved in various volumes, two of his famous works are the Nichmachean Ethics and the Politics, both of which contain a rich compilation of ethical and political thought. In the Ethics, Aristotle describes a thorough understanding of ethical and intellectual virtue. By pursuing these virtues, Aristotle argues that a person can achieve a life of fulfilling happiness. The ideal polis as described in the Politics serves as a place where the virtuous life is attained in the best manner.Citizens who pursue virtue make the polis better, and the rulers that guide the polis ensure that the citizens have every opportunity to pursue the virtuous life. In this thesis, I see how relevant Aristotle's theory is by laying out the basic principles of the Ethics and the Politics and the connections between the two works. Indoing so, I found that Aristotle's ideal theory points out a significant flaw in our political system: the fact that we do not share a common moral conception such as the one concerned with the virtuous life as Aristotle proposes. This does not suggest thatAristotle's view was actualized during his time period, but that Aristotle conceives of an ideal life and an ideal polis that could be realized. Certainly there are issues with Aristotle's thesis concerning the inferiority of slaves and women. But what is morepoignant is the impracticality of instituting a shared common conception when today's political system permits various ideas about ethics and morality.

Study Of The Binding Of Substrate By The Phe557Val Mutant Soybean Lipoxygenase-1

Lipoxygenases are a class of enzymes which consist of non-heme iron dioxygenases that are produced by fungi, plants, and mammals and catalyze the oxygenation of polyunsaturated fatty acid substrates to unsaturated fatty acid hydroperoxide products. The unsaturated fatty acid hydroperoxide products are stereo- and regiospecific. One such lipoxygenase, soybean lipoxygenase-1 (SBLO-1), catalyzes the conversion of linoleate to 13-hydroperoxy-9(Z),11(E)-octadecadienoate (13-HPOD) and a small amount of 9-hydroperoxy-10(E),12(Z)-octadecadienoate (9-HPOD). Although the structure of SBLO-1 is known and it is the most widely studied lipoxygenase, how it binds to substrate is still poorly understood. Two competing binding hypotheses that have been used to understand and explain the binding are the head first binding model and the tail first binding model. The head first binding model predicts linoleate binds with its polar carboxylate group in the binding pocket and the methyl terminus at the surface of the binding pocket. The tail first binding model predicts that linoleate binds with its methyl terminus end in the binding pocket and the polar carboxylate group at the surface of the binding pocket. Both binding models have been used in the explanation of previous work. In previous work the replacement of phenylalanine with valine has been performed to produce the phe557val mutant SBLO-1. The mutant SBLO-1 was then used in the enzymatic oxygenation of linoleate. With this mutant, the amount of 9-HPOD that is formed increases. This result has been interpreted using the head-first binding model in which the smaller valine residue allows linoleate to bind with the polar carboxylate group of linoleate interacting with arginine-707. The work presented in this thesis confirms the regiochemical results of the previous work and further tests the head-first binding model. If head-first binding occurs, the 9-HPOD is expected to have primarily S configuration. Utilizing chiral-phase HPLC, it was found that the 9-HPOD produced by the phe557val mutant SBLO-1 is primarily S, consistent with head-first binding. The head-first binding model was also tested using linoleyl dimethylamine (LDMA), which has been shown to be a good substrate for SBLO-1 at pH 7.0, where LDMA is thought to be positively charged. This model predicts that less of the 9-peroxide should be produced with this substrate. Through the use of gas chromatography/mass spectrometry, it was found that the conversion of LDMA by the phe557val mutant SBLO-1 resulted in the formation of a 46:54 mixture of the 13-peroxide:9-peroxide. The higher amount of 9-peroxide is the opposite of what is expected for the currently proposed model suggesting that the proposed model may not be entirely correct. The results thus far have been consistent with reverse binding but not with the proposed interaction of the polar end of the substrate with arginine-707.

Representations of the Human/ Nonhuman Primate Divide: the Influence of Science, Fiction, and Science-Fiction on the Concept of 'Being Human'

For as far back as human history can be traced, mankind has questioned what it means to be human. One of the most common approaches throughout Western culture's intellectual tradition in attempts to answering this question has been to compare humans with or against other animals. I argue that it was not until Charles Darwin's publication of The Descent of Man and Selection in Relation to Sex (1871) that Western culture was forced to seriously consider human identity in relation to the human/ nonhuman primate line. Since no thinker prior to Charles Darwin had caused such an identity crisis in Western thought, this interdisciplinary analysis of the history of how the human/ nonhuman primate line has been understood focuses on the reciprocal relationship of popular culture and scientific representations from 1871 to the Human Genome Consortium in 2000. Focusing on the concept coined as the "Darwin-Müller debate," representations of the human/ nonhuman primate line are traced through themes of language, intelligence, and claims of variation throughout the popular texts: Descent of Man, The Jungle Books (1894), Tarzan of the Apes (1914), and Planet of the Apes (1963). Additional themes such as the nature versus nurture debate and other comparative phenotypic attributes commonly used for comparison between man and apes are also analyzed. Such popular culture representations are compared with related or influential scientific research during the respective time period of each text to shed light on the reciprocal nature of Western intellectual tradition, popular notions of the human/ nonhuman primate line, and the development of the field of primatology. Ultimately this thesis shows that the Darwin-Müller debate is indeterminable, and such a lack of resolution makes man uncomfortable. Man's unsettled response and desire for self-knowledge further facilitates a continued search for answers to human identity. As the Human Genome Project has led to the rise of new debates, and primate research has become less anthropocentric over time, the mysteries of man's future have become more concerning than the questions of our past. The human/ nonhuman primate line is reduced to a 1% difference, and new debates have begun to overshadow the Darwin-Müller debate. In conclusion, I argue that human identity is best represented through the metaphor of evolution: both have an unknown beginning, both have an indeterminable future with no definite end, and like a species under the influence of evolution, what it means to be human is a constant, indeterminable process of change.

Sexing the Male: Manifestations of Masculinity in Jane Eyre, Wuthering Heights, and Villette

Abstract: This project considers Emily and Charlotte Brontë's constructions of masculinity in Jane Eyre, Wuthering Heights, and Villette. There is a vast proliferation of scholarship focusing on gender in the Victorian Era, but as much of this criticism focuses on women, the analysis of heterosexual masculinity in these novels provides a unique perspective on the complexities involved in gender constructions during this period. Masculine identity was in a transitory state in the early nineteenth century, as Romantic values were replaced by Victorian conceptions of masculinity, largely influencing the expectations of men. This paper argues that based on an understanding of femininity and masculinity as defined in relation to each other, the Brontë heroes look to the female characters as a source of stability to define themselves against, constructing a stagnant feminine role to frame an understanding of how masculinity was changing. The female characters resist this categorization, however, never allowing the men to fully classify them into stable feminine roles, which leads both shifting gender roles to intertwine and collapse in the novels, undermining any conceptualization of a stable or universal understanding of gender. The paper considers the role of masculinity based in class, relationships with women, and the understanding of sexual passion, to argue that the Brontës' portrayal of men emulates the anxieties surrounding the shift from Romantic to Victorian values of manliness, ultimately rejecting any stable definition of the nineteenth-century man.