Alumni Dissertations

 

Alumni Dissertations

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  • DNA Adducts of 10-decarbamoyl Mitomycin C Activate p53-dependent and p53-independent Cell Death

    Author:
    Ernest Boamah
    Year of Dissertation:
    2009
    Program:
    Biology
    Advisor:
    Jill Bargonetti
    Abstract:

    Mitomycin C (MC), a natural antibiotic and DNA cross-linking agent, has cytotoxic activity and is known to activate the tumor suppressor p53 protein. 10-decarbamoyl mitomycin C (DMC), a derivative of MC, has increased cytotoxicity compared to MC. Both MC and DMC induce cellular cytotoxicity in cells with wild-type p53, while only DMC shows significant cell death activity in the absence of wild-type p53. We investigated the difference in MC and DMC cytotoxicity by comparing DNA adduct composition and the cellular regulation of molecular targets in human cancer cell lines with or without wild-type p53. Compared to MC, DMC produced substantially more mitosene-1-β mono and 1-β cross-link adducts in DNA and resulted in abnormal nuclear morphology in human cancer cells with or without p53. Significantly, greater poly(ADP-ribose)polymerase (PARP) activity was observed after DMC treatment in both the presence and absence of wild-type p53. Both MC and DMC induced double strand breaks as indicated by gamma-H2AX foci formation irrespective of the p53 status, suggesting that double strand breaks cannot account for DMC's increased cytotoxicity. In cell lines expressing wild-type p53, both MC and DMC signaled for p53 stability and apoptosis induction resulting in cleavage of procaspase-3 and -8. Despite the DMC induced cellular cytotoxicity observed in cell lines lacking wild-type p53, cleavage of procaspase-3 or -8 was not observed in these cells. However, we observed an increase in caspase activity. Caspase-2 activation has been suggested as a pathway for p53-independent cell death in the absence of Chk1. Interestingly, Chk1 was depleted following DMC, but not MC treatment in cells with or without wild-type p53. This Chk1 depletion was achieved through the ubiquitin proteasome pathway since chemical inhibition of the proteasome protected against Chk1 depletion. Additionally, gene silencing of Chk1 by siRNA increased the cytotoxicity of MC but not of DMC. DMC treatment also caused a decrease in the level of total ubiquitinated proteins without increasing proteasome activity. This suggests that DMC- mediated DNA adducts facilitate signal transduction to a pathway targeting proteins for proteolysis. In conclusion, we have found that DMC generates significantly more mitosene-1-β stereoisomeric DNA adducts than MC and causes rapid down-regulation of multiple cellular targets. These studies suggest increased mitosene-1-β stereoisomeric DNA adducts more effectively signal for a mode of cell death which does not require a functional p53 protein.

  • The Value of Diversity: Culture, Cohesion, and Competitiveness in the Making of EU-Europe

    Author:
    Katharina Bodirsky
    Year of Dissertation:
    2012
    Program:
    Anthropology
    Advisor:
    David Harvey
    Abstract:

    This dissertation examines a particular way of governing (through) "culture" as a means to reflect on the making of a "non-national" state form (EU-Europe) and its implications for social inequalities. The term EU-Europe highlights complex and often conflictual relations between European Union (EU), national, and regional governmental levels, and the study focuses on relations between the EU and the city of Berlin. The dissertation critically examines the development of a policy common sense that emphasizes the potential value of cultural diversity for economic competitiveness. Such value, it is assumed by policy-makers, can be realized by combining support to the creative and cultural industries with an approach to immigrant integration that respects individual cultural diversity, ensures equality of opportunity, and fosters intercultural dialogue. Because such interculturalism goes on the EU level hand in hand with a new narrative of EU-Europeanness, the study also "moves outwards" onto relations of EU accession established with Turkey where this has been articulated particularly clearly. The study argues that interculturalist policy constitutes an attempt to overcome challenges to legitimacy and cohesion on EU and city levels by establishing "non-national" modes of belonging and entitlement that work with the neoliberal agenda that has dominantly informed EU-European state-making of the last decades. In selectively embracing cultural diversity, such policy is to turn "culture" from a problem into a resource in the making of "cosmopolitan" places conducive to capital. In Berlin, this has fed into processes of gentrification that serve the generation of rent and effectively void the "right to place" of populations marked through class and culture. In the politics of Turkey's EU accession, the claim that EU-Europeanness is defined through an embrace of diversity has in turn obscured and enabled EU support of the development of a Turkish "competition state." The dissertation furthers our understanding of contemporary "non-national" forms of statehood and of the ways in which these (re)produce inequalities between people and places. It is based on extensive analysis of policy and political documents, interviews with key policy-makers, attendance of policy events, and experience of local politics in Berlin gained during a stay of 12 months.

  • Straight Record and The Paper Trail: From Depression Reporters to Foreign Correspondents

    Author:
    Magdalena Bogacka-Rode
    Year of Dissertation:
    2014
    Program:
    English
    Advisor:
    Jane Marcus
    Abstract:

    Straight Record and the Paper Trail: From Depression Reporters to Foreign Correspondents engages with Martha Gellhorn's The Face of War (1959), Virginia Cowles' Looking for Trouble (1941) and Josephine Herbst's The Starched Blue Sky of Spain and Other Memoirs (1991) as documentaries of struggle. Documentary as a mode of writing and image making reveals dissonance, contradictions and varied perspectives which undermine the official historical record. The three writers, I argue, by republishing their Spanish Civil War (SCW) journalism in book form intended to set their record straight. This was motivated by their commitment to the 1930s struggle and the need to recover much that had been relegated to the margins as human interest stories (HIS), or woman's angle. This patronizing and denigrating label which was applied to their SCW articles dismissed the documentary value of, what I call, their human experience record (HER), as an affectation of uninformed and class biased women writers. Their documentary texts, much like those of Nancy Cunard, Muriel Rukeyser, Gerda Taro, Gamel Woolsey and Virginia Woolf, were not composed under auspices of dominant party lines as they eschewed formal membership in political as well as international organizations. In these, they recognized the very same patriarchal constraints and limitations which they sought to expose using the `masters' tools' they acquired by belonging, or at least being able to pass for "daughters of educated men" yet remained fully aware that being citizens with passports they were in position to help, but by no means to become the face of the cause(Woolf). The main criticism of The Face of War, Looking for Trouble and The Starched Blue Sky of Spain and Other Memoirs has been that Gellhorn, Cowles and Herbst did not tell the whole truth, that dates and names of key players are missing, and that they had no definite answers about the politics and propaganda in Spain. But these were not the objectives these women set for themselves when they went to Spain and later when they decided to republish their SCW journalism. What Gellhorn, Cowles and Herbst omitted from journalism and their subsequent accounts in book form -- moments of doubt, consternation, idleness -- remains in their archival repositories, the recovery project of which this dissertation aims to initiate.

  • Parental Investment and Song Learning in Zebra Finches (Taeniopygia guttata)

    Author:
    Diane Bogdan
    Year of Dissertation:
    2009
    Program:
    Psychology
    Advisor:
    Cheryl Harding
    Abstract:

    Abstract PARENTAL INVESTMENT AND SONG LEARNING IN ZEBRA FINCHES (TAENIOPYGIA GUTTATA) By DIANE M BOGDAN Adviser: Professor Cheryl F. Harding In order to understand the effects of parental investment on learning, we conducted a series of experiments using zebra finches. The aspects of parental investment studied included deposition of maternally-derived hormones (MDH) into eggs, feeding and attention to chicks. Learning was assessed by song copying (mean accuracy, sequential matching and percent similarity to the father's song). We compared digit ratios, a marker for the amount of MDH chicks experienced in eggs, and song copying ability. Our data suggests that maternally-derived testosterone negatively affected the ability to sequentially match notes. To determine if parents were preferentially feeding chicks by hatch order, we weighed chicks at key developmental points prior to fledging. We found that chicks that hatched early were heavier than those who hatched late. Additionally, weight at day 10 was positively correlated with song learning. Acoustic cues are one obvious way that parents might differentiate chicks by hatch order. Therefore, we assessed the begging calls of 10 day old chicks. We found that early-hatched chicks begged at lower amplitudes than late-hatched chicks. We then conducted a playback experiment in which begging calls of 10 day old early- and late-hatched chicks were presented to breeding adults. Adults were more attentive during the early-hatched chicks' playbacks. To determine if attention, in the form of clumping or perching closely together, affected song learning, we observed family groups when chicks were beginning song acquisition (day 25). We found that while clumped with their mates, mothers clumped with first-hatched more than second- or third- hatched chicks. Moreover, clumping behavior was positively correlated with the percent similarity of song copying. Clumping with first-hatched sons may be a way for mothers to give additional access to the father and thereby enhance son's song learning. Finally, we used a multiple linear regression, combining all three forms of parental investment to determine which were more important in song learning. We found that digit ratio 2:3 was positively correlated with sequential matching, nestling weight positively correlated with mean accuracy and clumping with the mother positively correlated with the percent similarity score.

  • PREDICTING INTRODUCTIONS AND RANGE EXPANSIONS OF THE MONK PARAKEET WITH ECOLOGICAL NICHE MODELING AND LANDSCAPE GENETICS

    Author:
    Corentin Bohl
    Year of Dissertation:
    2013
    Program:
    Biology
    Advisor:
    Jason Munshi-South
    Abstract:

    The ability to predict species future geographic distributions is an important challenge in biogeography and conservation biology, with critical implications for pressing environmental issues, including the potential spread of invasive species. This research examines a two-step framework to build accurate predictions of the invasive potential of the monk parakeet (Myiopsitta monachus). This species, native to temperate South-America, has established several stable populations worldwide, and shares many of the typical traits of high-risk invaders. The proposed framework aims to 1) identify areas where the species is likely to thrive, and 2) determine which of these suitable areas the species can likely disperse to. Objective 1 requires identifying the environmental conditions suitable to the species, for which I used ecological niche modeling (Chapter 1 & 2). Objective 2 addresses the ability of the species to conquer new adjacent favorable areas via dispersal, a problem that can be addressed with landscape genetics (Chapter 3). In Chapter 1, I developed a null model approach to evaluate the performance and significance of ecological niche models. The results highlight the importance of accounting for both discrimination and overfitting and correctly estimating significance. In Chapter 2, I tested the effect of different model calibration strategies on transferability (the ability to predict independent data in different geographic regions). I used this information to make predictions about the global invasive potential of the monk parakeet. The best prediction was obtained with native calibration records and complex model settings. This prediction indicates several areas with conditions suitable for monk parakeets, including areas adjacent to existing introduced populations. In Chapter 3, I integrated ecological niche modeling and landscape genetics to make predictions about the landscape features that affect monk parakeet dispersal. I tested these predictions with genetic data from an introduced population in Florida, and assessed their significance with null models. Estimating resistance to dispersal with ecological niche modeling produced results equivalent to evaluating a range of alternative hypotheses with a stepwise regression model. The results indicate that monk parakeet may not be limited by distance and most landscape features and are likely to expand to adjacent suitable areas.

  • The Characterization of Black Inkjet Computer Printer Inks using Pyrolysis Gas Chromatography-Mass Spectrometry (Py-GC-MS), High Performance Liquid Chromatography (HPLC), Thin Layer Chromatography (TLC) and Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR FT-IR)

    Author:
    Michelle Boileau
    Year of Dissertation:
    2012
    Program:
    Criminal Justice
    Advisor:
    Thomas Kubic
    Abstract:

    Documents are prevalent in every aspect of daily life and hardly a day passes without using some sort of document. Problems arise, however, when the authenticity of these documents is raised. Forensic science has long been involved in the investigation and examination of suspect documents. One of the steps in the examination of questioned documents is for the examiner to analyze the type of material used to create the document. This could involve the analysis of the paper substrate and/or the medium used to create the written word, namely pen ink, typewriter ink or toner in photocopied documents. This is the age of the computer, and as a result new challenges are facing the questioned document examiner. With more and more individuals using computers to produce their documents, and with the advancement of more sophisticated computer and printer systems, it has become harder for the analyst to distinguish and possibly individualize a suspected document based on physical appearance alone. Once again, the forensic scientist must focus on the material used to produce the document, namely the computer printer ink. An examination of these ink samples may allow for the differentiation between the many manufacturers, as well as within the products of a specific manufacturer. In time, it may also be possible to date a computer printer generated document based on the drying and decomposition rates of the different computer printer ink components. Currently, this is unfortunately still just a theory. There have been few studies on the different types of computer printer inks and how, or if, they differ from each other. The identification of the various black inkjet computer printer ink manufacturers, and the creation of a classification procedure, is the first step in the analysis of a questioned inkjet produced document. The goal of this study was to produce a detailed document on the forensic identification of black inkjet computer printer inks, and this research succeeded in its goal. The analysis of the black inkjet computer printer ink samples by Thin Layer Chromatography (TLC), High Performance Liquid Chromatography (HPLC), Pyrolysis Gas Chromatography-Mass Spectrometry (Py-GC-MS) and Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR FT-IR) analytical methods resulted in the production of data that led to the establishment of a classification procedure that could assist the forensic scientist in the examination, identification and discrimination of the different inkjet computer generated documents they receive.

  • CANDIDA ALBICANS ALS5P AMYLOID IN HOST-MICROBE INTERACTIONS: A CEANORHABDITIS ELEGANS STUDY

    Author:
    MICHAEL BOIS
    Year of Dissertation:
    2014
    Program:
    Biology
    Advisor:
    PETER LIPKE
    Abstract:

    Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces cerevisiae expressing Als5p on the surface. Als5p-expressing yeast had increased intestinal accumulation rates when compared to non-expressing S. cerevisiae or yeast expressing the amyloid deficient Als5pV326N, respectively. Surprisingly, this accumulation delayed S. cerevisiae-induced killing of C. elegans. Treatment with the amyloid-inhibiting dye Congo red or repression of Als5p expression abrogated the protective effect of Als5p. Being that reproductive fitness is the most important measure of a pathogen's impact on the host, we looked at oocyte quantity and quality[3]. Als5p had no effect on oocyte quantity or quality. In order to understand why nematodes exposed to Asl5p were able to harbor the cells expressing functional amyloid, we looked into the innate immune system of the nematode. Toll- Like receptors (TLRs) are important mediators of innate immune responses to Candida albicans, and several classes of scavenger receptors have been implicated in recognizing and reacting to a variety of ligands in humans[4]. The C. elegans genome encodes for a single TLR, TOL-1, and scavenger receptor CED-1[4,5]. CED-1 is the orthologue to mammalian scavenger receptor SCARF1 and is required for defense against Cryptococcus neoformans[4,6]. Our studies showed that CED-1 was necessary for prolonged survival in the presence of Als5p, and TOL-1 was required for death in C. elegans fed S. cerevisiae. We have further demonstrated the necessity of CED-1 and TIR-1 in phosphorylation of ERK-2/MPK-2. The SAM and TIR domains of TIR-1 were shown to be necessary in discriminating the presence of functional amyloid, and thus elicit specificity in downstream signaling. Remarkably, the presence of the HEAT/Armadillo domain, alone, was sufficient to increase levels of phosphorylated ERK-2/MPK-2 in nematodes fed any yeast strain in this study. This study is the first to show that expression of amyloid-forming Als5p in S. cerevisiae can: a) attenuate S. cerevisiae pathogenicity in C. elegans; b) move the yeast-host interaction towards hallmarks of commensalism; c) be discriminated against by host pathogen recognition receptors (PRRs) leading to a slower decline in viability; and d) can lead to distinct downstream MAPK responses.

  • The Interchange of Plain Velar and Aspirate in Kronos/Chronos: A Case for Etymological Equivalence

    Author:
    Roberto Bongiovanni
    Year of Dissertation:
    2014
    Program:
    Classics
    Advisor:
    Tamara Green
    Abstract:

    Despite the current state of uncertainty regarding the etymology of Kronos, the equivalence long familiar to the ancients between Kronos and Chronos is still a moot point. Arguments denying their etymological equivalence can no longer firmly rely on linguistic arguments. It is therefore necessary to examine the validity of the time-honored interpretation of Kronos as the personification of Time. The solution to this problem is of considerable importance to Classical studies, since it will not so much as contribute to a better understanding of the myth of Kronos, as the interpretation of Kronos as Time is already familiar from ancient sources, but it will demand a rereading of Hesiod's Theogony to account for the possible relation of its myth and symbols to comparable myths and symbols of the transitioning ages of the world and consequent calendrical corrections.

  • Manuel de la Cruz González: Transnationalism and the Development of Modern Art in Costa Rica

    Author:
    Lauran Bonilla-Merchav
    Year of Dissertation:
    2014
    Program:
    Art History
    Advisor:
    Anna Indych-López
    Abstract:

    While scholars are increasingly scrutinizing twentieth-century Latin American art and inserting it into the canon of modern art history, studies of the region usually leap from Mexico to South America, skipping Guatemala, El Salvador, Honduras, Belize, Nicaragua, Costa Rica, and Panama. This is not due to a lack of dedicated artistic effort in the isthmus, but rather to poor cultural infrastructure, which made being a modern artist in the region particularly challenging, and the underdeveloped state of local art histories, which have yet to traverse national borders. This oversight of Central American art makes it difficult to grasp the full scope of Latin America's adaptation of, and contribution to, international modernism. My dissertation counteracts the privileging of art from North and South America and introduces Costa Rican art history to an international audience by examining the art and life of Manuel de la Cruz González Luján (1909-1986), one of Costa Rica's most influential modern artists. It emphasizes the importance of the transnational cultural currents that influenced González and his colleagues, and systematically discusses two fundamental phases of artistic growth in the country, the 1930s and the 1960s. By placing González's artistic production within the socio-historic, cultural, and aesthetic contexts of Costa Rica, this dissertation is a groundbreaking case study of the development of modern art in this Central American nation. González prodded the boundaries of the provincial Costa Rican art world and moved beyond local frameworks to take part actively in the spread of modernist trends. He embraced regionalism, modernismo, and Latin American impressionism while in Costa Rica, and surrealism and geometric abstraction during the ten years he spent abroad in Cuba (1948-1950) and Venezuela (1950-1957). Upon his return, he shared his knowledge and experience of international modernism, but was faced with an unprepared and unpropitious artistic setting that neither accepted nor encouraged his geometric abstract art. What his story shows is that in order for a transnational style or idea to take hold in a country such as Costa Rica, which could be any "ex-centric" location, it is necessary to have a receptive context. This analysis of González's career thus highlights the tension of being a provincial artist, attuned to transnational cultural flows, yet challenged by the limitations of his environment.

  • Systematic Asymmetries in Perception and Production of L2 Inflections in Mandarin L2 Learners of English: The Effects of Phonotactics, Salience, and Processing Pressure on Inflectional Variability

    Author:
    Timothy Bonner
    Year of Dissertation:
    2013
    Program:
    Linguistics
    Advisor:
    Gita Martohardjono
    Abstract:

    The study of language production by adults who are learning a second language (L2) has received a good deal of attention especially when it comes to omission of inflectional morphemes within L2 utterances. Several explanations have been proposed for these inflectional errors. One explanation is that the L2 learner simply does not have the L2 syntactic or prosodic representation in his grammar leading to omission of surface inflections (Hawkins & Liszka, 2003; Goad, White, & Steele, 2003, respectively). Others attribute L2 errors to mapping problems between the lexicon and syntax (Prévost & White, 2000; Lardiere, 1998, 2003). Another potential explanation for the variable production of inflectional endings is that it may be due to performance factors as in Hopp (2009) and Martohardjono, Valian, and Klein (2012) or to "Extra-syntactic" factors as proposed in Klein (2004) or to syllable repairs due to L1 phonotactic interference as proposed in Davidson (2005, 2006a, 2006b). This dissertation claims that when L2 morphosyntactic representations are shown to be available in the L2 learner's grammar, L2 inflectional variability can be attributed to L1 phonotactic interference, salience of the L2 inflection, and performance factors leading to systematic, but asymmetrical patterns of perception and production of the allomorphs that represent the surface L2 inflections. The results revealed that the target inflections were not omitted across the board as would be expected under deficit accounts. On the contrary, repairs of the final target coda clusters (i.e., schwa epenthesis before and after the final inflectional consonant and devoicing of the word-final consonants) revealed patterns that are consistent with the degree of syllabicity (e.g., [Vd] vs. [t] and [d]) and sonority (e.g., [s] vs. [t]) of the allomorph or coda and are not indicative of morphosyntactic deficits. Importantly, schwa epenthesis was applied asymmetrically (i.e., particularly to stops [t] and [d]) in clusters that contained target codas and inflectional allomorphs in real, nonce, and monomorphemic items, and thus, this repair pattern is contra the Prosodic Transfer Hypothesis of Goad et al. (2003). Overall, this dissertation presents an alternative explanation for L2 inflectional errors outside of the morphosyntactic and prosodic deficit arguments.