Alumni Dissertations

 

Alumni Dissertations

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  • Conformational features of the human U2-U6 snRNA complex

    Author:
    Ravichandra Bachu
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Nancy Greenbaum
    Abstract:

    The splicing of precursor messenger (pre-m) RNA, during which noncoding intervening sequences are excised and flanking coding regions ligated, is an integral reaction of gene expression. In eukaryotes, it is carried out by a dynamic RNA-protein complex called the spliceosome, in which five small nuclear (sn) RNA components are actively involved in recognition and chemical aspects of the process. A complex formed between U2 and U6 snRNAs is implicated in the chemistry of pre-mRNA splicing. The catalytic activity of the U2-U6 snRNA complex is dependent on the presence of Mg2+ ions, and the complex has been shown to have several specifically bound Mg2+ binding sites in vitro. The overall goal of this research is to characterize the conformational changes of the human U2-U6 snRNA complex upon addition of Mg2+. In order to pursue this question, we attempted to characterize the lowest energy structure of the complex in the absence of spliceosomal proteins using a combination of biophysical and biochemical techniques in the solution state. We first used enzymatic structure probing to evaluate the secondary structural fold of protein-free human U2-U6 snRNA complex. Cleavage patterns resulting from probing reactions were consistent with formation of four stem regions surrounding the junction, therefore favoring the four-helix model consistent with previous results of in vivo studies of the human U2-U6 snRNA complex. However, 19F NMR studies from our laboratory also identified a lesser fraction (up to 14%) of a three- helix conformation. Upon addition of up to 100 mM Mg2+, a slight increase in cleavage by enzymes specific for both single-stranded and double-stranded regions was observed at the junction region, suggesting that this region is becoming more accessible, perhaps because of an increase in the fraction of the three-helix conformation. Analytical ultracentrifugation studies revealed that the Stokes radius of the RNA complex decreased slightly from 31.3 Å to 27.9 Å in the presence of 100 mM Mg2+, suggesting a slight compaction of the tertiary structure in the presence of divalent metal ions. Hydroxyl radical footprinting experiments on this complex showed signs of increased protection in some areas near and more distant from the junction upon addition of Mg2+, suggesting a change in three-dimensional conformation. Therefore, it appears that Mg2+ induces a small three-dimensional conformational change on human U2-U6 snRNA complex. In order to build a three-dimensional model for the four-helix conformation, we designed a mutant that favors the formation of four-helix conformation and performed SAXS experiments on it. The preliminary SAXS studies suggest that the human U2-U6 snRNA complex and the mutant complex may also be amenable to further study by SAXS. These results act as a good starting point to characterize further the overall global conformation of human U2-U6 snRNA complex and effects of spliceosomal proteins on it.

  • Aesthetic Autobiography and The Poetics of Despair in Post-War American Literature

    Author:
    David Bahr
    Year of Dissertation:
    2012
    Program:
    English
    Advisor:
    Wayne Koestenbaum
    Abstract:

    This dissertation repositions "aesthetic" in its ancient Greek context, meaning to apprehend by the senses. The project is framed around my idea of the aesthetic autobiography, a creative work that phenomenologically conveys the embodied experience of its author. I do not use "aesthetic" as a transcendentalist term of critical assessment, as defined by Kant; instead, the term denotes the immanent realm of the senses. This move allows me to connect the aesthetic to affect, whose etymology I trace from the mid 18th Century to contemporary affect theory. I theorize the aesthetic as a dynamic and relational biophysical force. I aim to extend the boundaries of autobiographical "truth" in order to accommodate the feeling body, which exists in excess and often beyond the reach of conceptual language. Specifically, I examine how five post-war authors formally confront the challenge of conveying the sensation of depression. By focusing on formal experiments in rhythm, syntax, structure, imagery, and genre, I look at texts by Allen Ginsberg, Joan Didion, Tim O'Brien, Art Spiegelman, and Darryl Cunningham. Grounding the project in mid-twentieth century America, chapter 1 begins with Edmund Wilson's "The Wound and the Bow" (1941), which situates the psychologically wounded artist as a vital and connective social force. In chapters 2 and 3, I juxtapose the respective approaches of Ginsberg and Didion in articulating the physiological experience of a depressive breakdown. Chapter 4 focuses on The Things They Carried, by Tim O'Brien, as a self-consciously constructed aesthetic autobiography: I show how "postmodernism" responds to representing the sensational body after the "death of the subject" and I argue for its affective possibilities. Finally, in chapter 5, I turn to graphic memoir, with Art Spiegelman's "Prisoner on the Hell Planet" and Darryl Cunningham's Psychiatric Tales: 11 Graphic Narratives of Mental Illness. I explore the formal strategies available to cartoonists in conveying the bodily affect of despair

  • Genetically Modified Collagen-like Triple helix Protein as Biomimetic Template to Fabricate Metal/Semiconductor Nanowires

    Author:
    Hanying Bai
    Year of Dissertation:
    2011
    Program:
    Chemistry
    Advisor:
    Hiroshi Matsui
    Abstract:

    Various metal and semiconductor nanowires have been developed as building blocks for electronics, optics, and sensors devices. Among these, new nanowires developed on biomolecular templates got more attention since the molecular recognition functions of these biomolecules with specific ligands can be employed to immobilize nanowires onto specific locations to establish desired device geometries. In order for their application in electronics, optics, and sensors device fabrications, after configuring device geometries with nanowires by the biomolecular recognition, we focused upon the biomineralization function of peptides on the nanotemplate sidewall to develop various material coatings such as metals and semiconductors for electronics and sensor applications. It should be noted that the coating morphology such as particle-domain size and inter-particle distance on the nanotemplates could be tuned by peptide sequences and conformations. We launched the genetically modified recombinant collagen-like triple helix proteins as a biorecognition, size-controlling and rigid biotemplate. This collagen-like triple helix is the genetically engineered polypeptide assembly that contains a fragment from the natural collagen sequence and has attractive features in hybrid nanomaterials. The length of the protein nanowire is uniform since it is determined by the number of amino acids. The length can be flexible if we genetically modify the sequence, which can also add chemical functionality by the genetic engineering procedure. Genetic engineering is more advantageous than the chemical synthesis for the functionalization /deritivization of peptide nanowire because only the desired specific residue of the peptide is functionalized by the genetic approach. The specific sequence can also increase stability so that the mechanical property can be tuned to be suitable for device application in harsh environment. By using the recombinant technology, it is possible to design and amplify a collagen-like triple helix that is monodisperse, easily mineralized with metal/ semiconductor precursors, and therefore can be applied as a rigid biomolecular template for metal/semiconductor nanowire fabrications. Moreover the production of triple helix can be large scaled up by means of the cell multiplication. As continued work based on previous study of the application of C7 glycylglycine bolaamphiphilic peptide, the self-assembly of doughnut-shaped nanoreactors from monomer peptides with silica precursors was studied, and uniform size silica (SiO2) nanoparticles were obtained. Possible mechanism in terms of chelating and catalysis functions of the peptide was formulated.

  • The Geometry of Gauss' Composition Law

    Author:
    Yelena Baishanski
    Year of Dissertation:
    2010
    Program:
    Mathematics
    Advisor:
    Lucien Szpiro
    Abstract:

    Gauss' identification of a composition law for primitive integral binary quadratic forms of given discriminant D--which provides the set FD<\sub> of SL2<\sub>(Z) equivalence classes of such forms with a group structure--essentially amounts to the discovery of the class group of an order in a quadratic number field. We consider quadratic extensions of the field of rational functions k(u), where k is an algebraically closed field, and seek an analogue of Gauss composition in this context. A quadratic extension of k(u) corresponds to the function field of a curve C with affine model t2<\super> = D(u) for some polynomial D = D(u) in k[u], which is of odd degree if and only if C has a smooth ramified point at infinity. Focusing on this case--the analogue of quadratic number fields with one complex place at infinity--we extend the notion of the degree of a Weil divisor on a curve to Cartier divisors on C, and find a bijection between the set of SL2<\sub>(k[u])-equivalence classes of primitive forms with coefficients in k[u] of discriminant D, and the group Pic0<\super>(C) of isomorphism classes of degree zero lines bundles on C. In parallel fashion, we reinterpret the arithmetic case using Arakelov's invention of metrics associated to the infinite places of a number field. Given an invertible R-module L for R a quadratic ring of discriminant D and fraction field K, we have for each infinite place v of K a corresponding one-dimensional C-vector space Lv<\sub>, with a positive non-degenerate hermitian metric. Using a notion of degree of an invertible metrized module--which mirrors the notion of degree used in the geometric case, yielding in both cases a "product formula" deg(f) = 0 for a principal divisor (f)--we establish for D < 0 a bijection between FD<\sub> and the compactified Picard group Picc<\sub>0<\super>(R) of isometry classes of degree zero invertible R-modules.

  • IMPROVING THE TEACHING AND LEARNING OF SCIENCE IN A SUBURBAN JUNIOR HIGH SCHOOL:ACHIEVING PARITY THROUGH COGENERATIVE DIALOGUES

    Author:
    Eileen Baker
    Year of Dissertation:
    2010
    Program:
    Urban Education
    Advisor:
    Kenneth Tobin
    Abstract:

    The research in this dissertation focuses on ways to improve the teaching and learning of science in a suburban junior high school on Long Island, New York. The study is my attempt to find ways to achieve parity in my classroom in terms of success in science. The goal of parity is for all students to have equal opportunity to enjoy a basic education of high quality, achieve at high levels, and enjoy equal benefits from education. I was specifically looking for ways to encourage Black female students in my classroom and in other classrooms to continue their science education into the upper grades. The participants were the 27 students in the class, a friend of one of the students, and I, as the teacher-researcher. In order to examine the ways in which structure mediates the social and historical contexts of experiences in relation to teacher and student practices in the classroom, I used collaborative research; autobiographical reflection; the sociology of emotions; immigration, racialization, and ethnicity, and cogenerative dialogues (hereinafter, cogens, singular cogen) as tools. Cogenerative dialogues are a way for students and teachers to accept shared responsibility for teaching and learning. This study is of importance because of my school's very diverse student body. The school has a large minority population and therefore shares many of the characteristics of urban schools. In my study I look at why there are so few Black female students in the advanced science course offered by our district and how this problem can be addressed. I used a variety of qualitative approaches including critical ethnography and micro analysis to study the teaching and learning of science. In addition to the usual observational, methodological, and theoretical field notes, I videotaped and audiotaped lessons and had discussions with students and teachers, one-on-one and in groups. In the first year the cogenerative group consisted of two Black female students. In the second year of the study there were four Black and one White-Hispanic female students in the cogen group. Below, I discuss my journey toward a career in science education and explain how I became a teacher-researcher. In my research I studied the interactions of the students between lessons and during laboratory activities as well as the cogens themselves in order to get the data needed to identify the role of science cogens in the learning and teaching of science. The students both in my cogen and in my science class collaborated with me as we worked to create new culture through conversations. I also used cogens to examine the influence of immigration, race, ethnicity, and gender in my science class. The students in the cogen were native-born children of immigrants, known as the second generation and/or 1.5 generation. In the first year one of these students was the daughter of Jamaican-born parents and the other native Black. The students in the second year included one each of Haitian and Jamaican descent, one with Dominican parents, and two native Blacks. Interestingly enough, if I had not conducted the cogenerative dialogues, I might never have become aware of their ethnicities. The cogens helped me to become a better teacher by allowing me to understand what racialization was and how it impacted students as well as teachers. The cogens helped students voice their opinions in a manner and in a place that supported their understanding of both the similarities and differences among students in the class in addition to contradictions in their science class as well as in other nested fields. Contradictions are differences between people and groups that arise as a normal part of social life in the classroom (and elsewhere, of course), and I looked for ways to retain these differences as we learned to deal with them. I looked especially for contradictions that were evident between the larger culture of the school and that of the students in the cogen. I studied the dialectical relationship between agency and structure in my science class and within the cogenerative dialogue group. I found that as students gained agency, they were more successful in obtaining entry into accelerated science classes and succeeded in those classes. I found that some marginalized students were shut down in their classrooms. During the common planning time within the science department, we discussed the lack of minority students in our advanced science classes. I introduced the idea of cogens and described how they could encourage more students to become involved in the process of learning. Although my colleagues did not institute cogens with their students, they did listen to the ideas about culturally relevant teaching which I communicated, and, although I have not witnessed it myself, I was told by some of my colleagues that they were trying to address the cultural mismatch found in their classrooms. The science faculty and I spoke to administrative personnel, and they saw how their goals and ours were aligned. Soon, all stakeholders were on board: my chairperson, the science department, and the administration. For many Black female students in our district, access to advanced science classes was largely unavailable because students had not learned to communicate scientific literacy in ways that were recognized and acknowledged in our school district. My research supports the theory and research that point to the desirability of building positive emotional energy through chains of interactions and transactions that produce success among most, if not all, participants. This study increases the understanding of the structure of interactions in a science class by building understanding of the face-to-face encounters associated with organizing, establishing, and maintaining conversations. As a teacher-researcher, I found that cogenerative dialogues also helped to create emotional energy and student engagement as well as synchrony and entrainment among students in the cogen and in the classroom. A community of learners formed, and this contributed to a positive learning environment. This environment in turn produced positive emotional energy and community. Cogenerative dialogues became a tool to build community in my science class. It also became a tool to introduce a new way of teaching and learning to me as well as to my colleagues. I began discussing the use of cogens in my science department meetings so that, by understanding different ways of thinking and being, my colleagues and I might find ways to transform science education at our school. Becoming aware is an important step for teachers and students to use their cultural capital to eliminate practices that prevent students from connecting with science. In cogens teachers and students can identify important shared classroom experiences and together fashion new roles for each of them. Teacher-researchers can effect change in their classrooms and, by letting others in the school and academic community become aware of their research, effect change in other schools as well. The results of the latest Regents exam have convinced the administration, the math, and the science departments as well as other faculty members of my junior high school that, when all stakeholders are involved, change can happen. The students who had been marginalized were as successful in the advanced science classes as those who were not. My school district took note of this and proudly continues the program.

  • Dissecting the role of human PPR motif proteins in mitochondrial gene expression

    Author:
    Catherine Bangeranye
    Year of Dissertation:
    2010
    Program:
    Biochemistry
    Advisor:
    Serafin Piñol-Roma
    Abstract:

    Pentatricopeptide repeat (PPR) motif proteins constitute a growing superfamily of proteins that are broadly defined by the presence of one or more copies of a conserved 35 amino acid sequence, the PPR motif. They are particularly abundant in plants, and those whose function has been characterized have been implicated in several aspects of RNA metabolism in mitochondria and chloroplasts. In humans, PPR motif proteins are fewer in number. They include LRPPRC (Leucine-Rich PPR-motif -Containing protein), an RNA-binding protein that is a component of nuclear ribonucleoprotein (RNP) complexes that contain spliced mRNAs. Most of the LRPPRC, however, localizes predominantly to mitochondria, where it binds polyadenylated RNAs. Mutations in the lrpprc gene cause cytochrome c oxidase deficiency in Leigh Syndrome (LSFC), which is accompanied by a decrease in COXI and COXIII mitochondrial mRNAs. Our hypothesis is that LRPPRC is an essential trans-acting factor in mitochondrial mRNA metabolism. In order to address the function of LRPPRC in mitochondria, we isolated LRPPRC-associated mitochondrial RNP complexes (mtRNPs). Analysis of isolated mtRNPs shows that the mitochondrially-encoded mRNAs associate with LRPPRC. A reduction in LRPPRC levels using RNAi causes a parallel reduction in steady-state levels of mitochondrially-encoded mRNAs, but not of nuclear-encoded mRNAs. Thus, LRPPRC is an important factor for mitochondrial gene expression and is necessary for the accumulation of the mitochondrial mRNAs to which it binds. Using LRPPRC as a paradigm, we sought and analyzed other members of the PPR motif family in humans. Four other human PPR-motif proteins, PTCD1, PTCD2, PTCD3 and PTCD4, also localize in mitochondria. Moreover, some of these proteins also bind RNA and exist in the same complexes as LRPPRC. This indicates that the human PTCD proteins, as is the case with LRPPRC, are also involved in mitochondrial RNA metabolism, pointing to PPR motif proteins in humans as a novel family of trans-acting factors in mitochondrial gene expression. These findings open the way for an expanded and more detailed understanding of human mitochondrial gene expression, and for an exploration of the potential involvement of human PPR motif proteins in mitochondrial diseases, as has already been determined for LRPPRC.

  • Continuum and Molecular Dynamics Simulations of the Growth of a Vapor Bubble on a Heating Surface: Exploring the Mechanism of Nucleate Boiling Heat Transfer

    Author:
    Jinyong Bao
    Year of Dissertation:
    2011
    Program:
    Engineering
    Advisor:
    David Rumschitzki
    Abstract:

    Starting with a completely rewritten code for the conductively-driven quasi-static vapor bubble growth in an axisymmetric, cylindrical cell comprised of solid and liquid phase of finite thicknesses under small Reynolds, Peclet, Capillary and Bond numbers to verify L. Huang's (our prior Ph.D. student) earlier results, we couple the solution of the quasi-static problem with three simple, somewhat ad hoc models of contact line motion and relax the assumption of small Bond number to simulate the growth of an incipient bubble until gravity begins to slowly deform the vapor bubble and then to detach it from the solid heater surface. A simple physical theory is developed to explain that when the bubble density is not too high, the bubble volume vs time approaches a 3/2 power before gravity begins to deform its shape, independent of contact line motion models and system parameters such as the conductivity ratio of the liquid to solid and degree of wall superheat. On the other hand, contact line motion does have a significant effect on bubble deformation and detachment. Molecular dynamics (MD) is employed to determine the contact line motion in a nano-scale version of our three-phase system because MD not only includes heat transfer, but also fluid flow, which can remove many restrictions of the earlier continuum calculation in our nano-size system. Instead of nucleating a bubble by cavitation, we nucleate a vapor bubble by heating the bottom of the solid upon which the fluid sits at constant pressure. Under a uniform body force that, due to the scale of MD is far larger than terrestrial gravity, we then track the bubble's growth driven by heat transfer from the conducting heated solid until detachment. Its contact line motion is monitored and the effects of wettability of solid surface, temperature-slip of fluid-solid interface and the choice of the interaction between the solid and the fluid have also been discussed. Unfortunately, this temperature slip mitigates some of the effects of the contact line that the continuum modeling (without temperature slip) finds so crucial at macroscopic scales.

  • Neocontradictions: The Politics and Ideology of American Welfare State Decline

    Author:
    Darren Barany
    Year of Dissertation:
    2009
    Program:
    Sociology
    Advisor:
    Stanley Aronowitz
    Abstract:

    This study historically investigates the circumstances - economic, political, and ideological - out of which the American political culture would shift to the right and become hostile to welfare. It is in part a genealogy of contemporary welfare reform discourse, which is comprised by the synthesis of varied and contradictory components of conservative philosophy about family, work, responsibility, and the role of government. This study also contextualizes that discourse within the development of a conservative politico-ideological apparatus. Today's conservative movement in the United States is the fusion of other sub-strands of conservatism and has successfully defined the parameters of acceptable discourse around the issue of welfare. It has developed a large pool of resources, become adept in the arena of activist and electoral politics, built a vast infrastructure for the production and deployment of ideas, and established a resilient presence in the everyday lives of Americans. Therefore a study of the erosion of the American welfare state must trace the development of these ideas and the means by which they became policy orthodoxy. Argued here is that the conservative movement's success in affecting welfare reform can be attributed to two factors. Firstly, it can be attributed to the consolidation and organization of libertarian and traditionalist conservatism and to the mastery of ideological production by a conservative politico-ideological apparatus or policy planning network. Secondly, it can be attributed to the emergence of varied conservative ideas on work, family, equality, and personal responsibility as a new policy consensus which was itself a consequence of important transformations in social and economic conditions. The post-war conservative movement has been dynamic and has managed its own ideological tensions by continually refining its argument and perfecting its methods of framing issues. It has contributed to altering the political culture in relation to the welfare state and related issues The subjection of welfare state programs to ongoing critique has enabled the social safety net to become vulnerable to reforms which have gradually altered them to be more consistent with the shifting requirements of the economic system and elite preferences.

  • An Examination of Predictive Variables of Success in Mental Health Diversion Programs.

    Author:
    Virginia Barber Rioja
    Year of Dissertation:
    2009
    Program:
    Psychology
    Advisor:
    Thomas Kucharski
    Abstract:

    Diversion programs were developed to ease the overrepresentation of individuals with psychiatric disorders in the criminal justice system. These programs divert individuals with mental illnesses out of jails into community treatment. Despite the increased popularity of these programs, little is known about the psychosocial, psychiatric and psychological characteristics of the diverted individuals. In addition, despite the importance of using standardized assessment instruments pre-diversion, no published study has attempted to evaluate the utility of risk assessment instruments or measures of malingering, personality or psychopathology in diverted offenders. This investigation attempted to address this gap in the literature through three different studies that (1) described a sample of 61 defendants released from jail in terms of demographical, clinical, and criminological characteristics; (2) determined the utility of the HCR-20 violence risk assessment scheme and the Psychopathy Checklist: Screening Version (PCL: SV) in the prediction of diversion non-compliance, and recidivism in a sample of 120 defendants, and (3) identified alternative factors that help defendants succeed in diversion through a multiple case-study design. Results revealed that this sample consisted primarily of minority male defendants with extensive histories of prior arrests, significant histories of physical abuse, homelessness and suicidality, and co-morbid substance abuse and psychiatric disorders. The findings provided preliminary validation of the predictive validity of the HCR-20 and PCL: SV with defendants diverted to community treatment. The HCR-20 was found to be superior to the PCL: SV in predicting both non-compliance and recidivism, and the PCL: SV proved to be more useful in predicting recidivism than non-compliance. Results of multiple case-studies found a pattern of characteristics shared by participants who failed diversion regardless of HCR-20 results. These variables included history of physical abuse, family history of substance abuse or criminal behavior, levels of social support, and level of responsibility taken for the instant offence.

  • El modernismo desde dentro: Discurso de la "gente nueva" y campo literario en la prensa modernista madrileña (1897-1907)

    Author:
    MARIA SUSANA BARDAVIO ESTEVAN
    Year of Dissertation:
    2010
    Program:
    Hispanic & Luso Brazilian Literatures & Languages
    Advisor:
    William Sherzer
    Abstract:

    This dissertation examines the trajectory of modernist discourse between 1897 and 1907 and its impact on the process toward autonomy of Madrid's literary field. In the late nineteenth century, the failure of the liberal project and of positivism plunged European thought into what has been called the fin de siècle crisis. Spain participated fully in this process, generating a series of protest discourses that rejected the prevailing system. In the arts and literature in particular, this led to a number of trends aesthetically or ideologically opposed to the political system of the Restoration, to bourgeois values, to radical positivism and to realist aesthetics. The material and social conditioning factors greatly hindered the development of the new aesthetics. This caused the young writers to come together as a community of discourse conjoining the plurality of perspectives that characterized them under two basic principles: the defense of literary renewal and the rejection of the established powers. The constant struggle for these two assumptions laid the foundations for a symbolic revolution in the literary field. I understand modernism as the collective discourse that in the late nineteenth century started to make its way into the literary field and whose impact on it would be crucial in the process of autonomization. My study focuses on the public sphere of modernist discourse. I have examined mainly the modernist magazines published in Madrid between 1897 and 1907 because, compared to the consecrated press, they were the means by which the gente nueva could freely express and disseminate their opinions. Throughout the dissertation I explore the development of modernist discourse to show that it was not immutable, but that it was changing within the literary field. As it was gaining recognition, the modernist writers adopted literary positions that caused confrontations among themselves, leading to the breakup of the original community of discourse. However, they were still sharing the defense of the aforementioned principles, and when they finally imposed them and their discourse was perceived as legitimate by the whole field, a degree of autonomy hitherto nonexistent in the literary world was eventually reached.