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  • COMPUTATIONAL STUDIES ON INTERACTION BETWEEN SOME RECEPTORS AND LIGANDS OF TRANSFORMING GROWTH FACTOR-BETA SUPERFAMILY: DESIGN OF INHIBITOR(S) TO PROMOTE OSTEOGENESIS

    Author:
    Shaila Ahmed
    Year of Dissertation:
    2010
    Program:
    Biochemistry
    Advisor:
    Boojala Reddy
    Abstract:

    Transforming growth factor beta (TGF-β) superfamily members execute distinct and intricate roles in numerous biological events such as cell growth, differentiation, embryogenesis, immune responses, and morphogenesis etc. Diverse cellular responses are instigated by binding of these superfamily members to specific transmembrane serine/threonine kinase receptors on the cell surface and thereby activating specific pathways. As a result receptor-regulated Smad proteins are phosphorylated, followed by their complex formation with Co-Smad that together translocates into nucleus and leads to the initiation of transcription of target genes. Bone morphogenic proteins (BMPs), activins, Inhibins are the most important members of TGF-β family. When they exert their biological activity, they are sternly regulated by extracellular antagonists such as noggin, follistatin, CV2, and so forth that are expressed in close temporal and spatial proximity. Blocking these antagonists' interaction with their target receptor proteins helps to promote their respective biological responses when needed. This work is an attempt to use the current understanding of some of the receptors and ligands of TGF- superfamily members, namely BMPs, activins and inhibins and their antagonists such as noggin, follistatin, and crossveinless 2 (CV2) interactions through the analysis of their available complex structures to design small molecular inhibitors with an ultimate goal of promoting their respective biological responses. Noggin is a major natural extracellular antagonist to BMPs which binds to BMPs and blocks binding of them to BMP-specific receptors and thus negatively regulates BMP-induced osteoblastic differentiation. BMPs signal through heteromeric protein complexes composed of type I and type II serine/threonine kinase receptors. Preventing the BMP-2/noggin interaction will preserve free BMP-2 and enhance the efficacy of BMP-2 to induce bone formation. One part of this work is an attempt to use the current understanding of BMP-2, and its interaction with its receptors and antagonists, through the analysis of known structures in protein data bank (PDB), to design inhibitors of BMP-2/noggin interaction with the goal of lowering the dose of BMP-2 required in clinical applications to promote osteogenesis. Another TGF- superfamily member, the activin, exerts pivotal roles in male and female reproduction, and has powerful actions in growth and differentiation in various tissues. The ability of activins to assemble their receptor complex, however, is regulated by a number of extracellular binding proteins. Follistatin is one of the main inhibitors among them. Follistatin acts primarily by binding to activin and preventing its interaction with its receptor there by bio-neutralizes activin-mediated responses. Here our main hypothesis is to understand the activin interaction with its receptors and antagonist follistatin, through the available structures in PDB, to design small molecular binder that blocks activin/follistatin interaction with the goal of promoting BMP responsiveness of the cells. Crossveinless 2 (CV2), a member of Chordin family, is an extracellular modulator of BMPs which has a unique feature of having both the anti- and pro-BMP activity depending on the cellular context. The anti-BMP activity is directed by excessive dosage of CV2 that impedes the BMP-dependent differentiation of osteoblast and chondrocyte in cell culture and in certain developmental stages. Crystal Structure of BMP-2/CV2-VWC1 domain is available. Here, our main goal is to design a potential inhibitor of BMP-2/CV2 interaction to promote osteoblast differentiation leading to promotion of bone healing. We analyzed the available complex structures to identify contact region of CV2 with BMP-2. By using the binding information of BMP with its receptors from BMP-2/noggin studies, we performed virtual screening and identified several compounds that are likely to bind to CV2 and block BMP-2/CV2 interaction that may enhance the ectopic bone formation. Finally, by using the BMP-2 sequence fragments that are in contact with noggin, from the BMP/noggin complex structure, we designed several, di-, tri- and tetra-peptide combination structures and docked them onto respective binding sites on noggin with future goal to develop modified peptide mimetic compounds that may help blocking BMP/noggin binding to promote osteogenesis.

  • Biodiversity and Ethnography of Tea Management Systems in Yunnan, China

    Author:
    Selena Ahmed
    Year of Dissertation:
    2011
    Program:
    Biology
    Advisor:
    Charles Peters
    Abstract:

    This study investigates biodiversity and cultural practices associated with tea (Camellia sinensis (L.) O. Kuntze; Theaceae) management systems in Yunnan Province of southwestern China. Surveys were conducted in smallholder communities of six sociolinguistic groups (Akha, Bulang, Han, Hmong, Lahu, and Yao) that manage tea resources in forests, agro-forests, mixed crop fields, and terrace gardens. Interviews were carried out between 2006 - 2010 to identify the influence of socio-economic and policy variables on tea production and consumption patterns. Ecological plot sampling and ethnobotanical inventories were employed to characterize the composition, structure, and uses of tea management systems. Tea leaf samples were randomly selected within each plot for: (1) video morphometrics to measure six shape and size attributes, (2) high performance liquid chromatography (HPLC) to quantify nine catechin and methylxanthine compounds and, (3) amplified fragment length polymorphisms (AFLP) molecular marker analysis to assess genetic diversity. Results indicate a relationship between the perceived value of a commodity and a change of management practices, ecological knowledge, and land use. Findings demonstrate how variable management practices result in the loss, conservation, or enhancement of plant species richness and genetic diversity, and how smallholders variably benefit from diversity in their agro-ecosystems. Plant species richness was found in the order agro-forest edge > forest > agro-forest > mixed crop field > terrace gardens. Statistically significant variation was found in morphological, phytochemical, and genetic characters between the different types of tea management systems. Morphological diversity was found in the order agro-forest > mixed crop field > forest > terrace gardens, whereas genetic diversity was found in the order mixed crop field > agro-forest > forest > terrace gardens. HPLC data show that tea samples from agro-forests and mixed crop fields had greater mean Total Catechin Content (TCC) and mean Total Methylxanthine Content (TMC) compared to forests and terrace gardens. Results further demonstrate that management, processing, and preparation methods are related to the phytochemical profile, anti-oxidant activity, and flavor of tea. This study provides useful baseline data to examine long-term change linked to expanded market integration and an engagement of ecosystem ecology with anthropology.

  • Off-chip Bandwidth for Multicore Processors: Managing the Next Big Wall

    Author:
    Bushra Ahsan
    Year of Dissertation:
    2010
    Program:
    Engineering
    Advisor:
    Mohamed Zahran
    Abstract:

    Abstract Off-chip Bandwidth for Multicore Processors: Managing The Next Big Wall by Bushra Ahsan Adviser: Professor Mohamed Zahran As we approach billion transistors on chip, the number of on-chip cores is skyrocketing. With the number of on-chip cores increasing, the traffic generated from these cores is also increasing. Recent studies have shown that this surge of traffic in multicores is bad news for supercomputing design. This is due to off-chip contention amongst applications running on multiple cores. Traffic in a multicore system is divided into on-chip trac (traffic amongst cores) and off-chip traffic (traffic from chip to memory). The off chip traffic is mainly generated by on-chip cache hierarchy and is divided into traffic towards memory, due to writebacks, and from memory, due to read misses. There is a huge body of research on managing cache hierarchies, improving their performance and hence reducing the number of cache misses. Bandwidth requirement has always been of secondary importance. In the multicore and many-core era, this is no longer the case. The cache hierarchy designer must take into account both cache performance and traffic generated by the cache in order not to put pressure on the available bandwidth. If off-chip bandwidth is not managed, a 16 core machine will not give much performance benefit over a dual core machine. In most processor architectures, the cache hierarchy consists of several private caches per core, followed by a shared Last-Level Cache (LLC). This LLC is the last wall before hitting off-chip and is the cause of off-chip bandwidth traffic i.e the writebacks. LLC, therefore, is a highly important factor in off-chip traffic generation. We manage the LLC in order to attain overall off-chip bandwidth management in a multicore system. In this thesis various methods to improve bandwidth by reducing traffic towards memory are proposed. We present hardware and hybrid techniques of varying complexities that work in rhyme to manage bandwidth for multicores. All techniques proposed to save bandwidth require very little overhead and reduce off-chip traffic considerably while not effecting overall performance. By bandwidth management we come closer to the ultimate goal of supercomputer on chip.

  • Tragic Practice: Participatory Democracy and Activist Theatre in the U.S., 2006-2010

    Author:
    Linell Ajello
    Year of Dissertation:
    2012
    Program:
    Theatre
    Advisor:
    Jean Graham-Jones
    Abstract:

    In this dissertation, I develop a theory of inclusive democratic communication, partly by studying contemporary activist performances such as Poverty Simulation, a role-playing game in which social service and government workers switch places with the poor people who are their clients; and Iraq Veterans Against the War's "Operation First Casualty," in which soldiers perform the drills they have enacted in Iraq in public spaces in the U.S., such as Penn Station. I see these performances as exceptions within national discourse, in which poor people and soldiers are more often represented than represent themselves. In exploring the contributions that performances such as these could make to public perceptions of political and ethical issues, I develop a model of democratic communication based upon inclusion, self-representation, and equal interpretive authority. I analyze the performances I study as acts of democratic communication even though, in political science, scholarship on democratic communication excludes theatre and other expressive forms. I argue that the ethos and representational practices of liberal humanitarianism that undergird deliberative democracy explain its limits, and so I, following theorists such as Søren Kierkegaard, Walter Benjamin, Cornelius Castoriadis, Vaclav Havel, and others, "pearl dive" to tragedy as a pre-modern model of collective interpretation. I develop a concept of tragic political discourse, connecting scholarship on tragedy with scholarship on democracy. I draw upon Hannah Arendt's description of political speech and action, placing her values and criteria in dialogue with Jürgen Habermas and a legacy of exclusionary categories in theories of democracy and civic republicanism. Throughout the project, I develop a model of communication in which participants share equal interpretive authority and equal vulnerability to critique. Along with a theory of democratic communicative practice, I develop a model of judgment as processual, hinging upon an awareness of the partialness of one's own understanding.

  • Chemistry of 6-Monobrominated Indigo, MBI

    Author:
    Hiroko Ajiki
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Lou Massa
    Abstract:

    6-monobrominated indigo, MBI, is a component of a historically important and the most expensive colorant, Tyrian Purple. The colorant is remarkably stable under the sun, in the air and after extensive washing with water. The color is still vivid after thousands of years. Even though it has such a high stability, MBI and Tyrian Purple have color changes from purple to blue upon temperature changes. This color change has been known for long to certain people, but the mechanism of the color change was unknown. Tyrian Purple also has recently attracted interests for applications towards semiconducting material due to its ambipolar property and high stacking structure and towards its biomedical applications. Though other chemicals in the colorant have been studied and analyzed well, MBI is the least studied and understood chemical. The full investigation of the chemistry of MBI has been conducted and reported in this study.

  • Nickel-catalyzed cross-coupling reactions involving secondary and tertiary alkyl nucleophiles

    Author:
    Amruta Ajit Joshi
    Year of Dissertation:
    2014
    Program:
    Chemistry
    Advisor:
    Mark Biscoe
    Abstract:

    NICKEL-CATALYZED CROSS-COUPLING REACTIONS INVOLVING SECONDARY AND TERTIARY ALKYL NUCLEOPHILES by Amruta Ajit Joshi Advisor: Prof. Mark R. Biscoe In the first chapter, introduction of transition metal-catalyzed cross-coupling reactions has been given. These transition metal-catalyzed C-C bond forming reactions have been used extensively in organic synthesis. Among them, C(sp2)-C(sp2) bond forming reactions have been widely studied over decades. More recently, some reports have demonstrated the use of C(sp3) nucleophiles and electrophiles in cross-coupling reactions. However, use of secondary and tertiary alkyl nucleophiles has remained a challenge due to competitive β-hydride elimination and slow transmetallation of bulky secondary and tertiary alkyl organometallic nucleophiles. In the second chapter, the first general nickel-catalyzed Negishi reaction for the cross-coupling of unactivated, acyclic secondary alkylzinc halides and aryl and hetero-aryl iodides has been reported. This process is the first to overcome the β-hydride elimination problem inherent to the use of the analogous palladium-catalyzed processes. This method is very general and tolerates a wide range of functional groups. A detailed study of the effect of salt additives on these reactions has also been presented. In the third chapter, this work has been extended to the use of tertiary alkyl nucleophiles and the first metal-catalyzed Kumada cross-coupling reaction of tertiary alkylmagnesium halides and aryl bromides/triflates has been reported. This reaction has very wide substrate scope, and vinyl bromides and vinyl chlorides can also be employed as electrophiles. Here, the effect of catalyst hydration on the reaction yield and selectivity has been demonstrated. In the fourth chapter, a mild palladium-catalyzed reaction for the monoborylation of primary alkyl halides using bis(pinacolato)diboron as the boron source has been reported. This reaction is very general and can accommodate a wide range of functional groups. To increase the utility of this process, the crude borylation product has been converted into the corresponding boronic acid, trifluoroborate salt and another boronic ester. Aditionally, bis(neopentylglycolato)diboron has also been employed as the boron source.

  • Exchanging Affect: The Migrant Domestic Workers Market in Turkey

    Author:
    Ayse Akalin
    Year of Dissertation:
    2009
    Program:
    Sociology
    Advisor:
    Patricia Clough
    Abstract:

    Since the second half of 1990's, Turkey has received a migration flow of women from the postsocialist countries of Eastern Europe, the Caucuses and Central Asia, into the domestic work sector. The demand for the migrant domestics is mainly for their live-in services, which also distinguishes them from the indigenous domestics since the latter prefer working strictly as live-outs. The migrants' willingness to work as live-in's has consequently caused them to be employed in three subfields of domestic work; care giving for the elderly, care giving for children and housekeeping in suburban houses. This research explores the emergence and expansion of "the migrant domestic workers market" as an ethnic niche in Turkey in the postsocialist period when migration and employment relations have formed a mutually fostering alliance. It argues that the migrant domestics of postsocialist origin are not demanded for an inherent ability. Rather the demand for their labor is a consequence of a capacity that they acquire by turning into transnational migrants. In this process, their subjectivity that was earlier shaped by an upbringing in a formerly socialist system also gets molded by a state of "migrancy". The latter then causes them to serve their employers in a distinct way that is characterized by a specific type of labor, which in this research is called "availability".

  • Piezoelectric Energy Harvesting From Fluid Flow

    Author:
    Huseyin Dogus Akaydin
    Year of Dissertation:
    2012
    Program:
    Engineering
    Advisor:
    Yiannis Andreopoulos
    Abstract:

    The conversion of the kinetic energy of a fluid into electrical energy through flow-induced vibrations on piezoelectric structures is investigated. "Aeroelectromechanics" of flow-powered piezoelectric harvesters is introduced, the efficiency components are delineated, and the figures of merit are defined. Wind tunnel tests were performed on two kinds of harvesters: i) A cantilevered piezoelectric beam in the wake of a circular cylinder, ii) A cantilevered piezoelectric beam carrying a tip mass on its free end. The comparison of the two revealed the prime effect of aeroelastic efficiency in total efficiency. A semi-analytical model to account for strain transfer from a passive substrate to a piezoelectric patch through an elastic bonding layer was developed. It was shown that, under certain conditions, the electric output of the piezoelectric harvesters can be predicted based on strain measurements on test models built without using piezoelectric materials. The potential of turbulent boundary layers for energy harvesting was also investigated. Two flexible piezoelectric beams of different lengths were tested at various distances off the wall of wind tunnel at different flow speeds. It was found out that the power output is maximal when the beam is within a certain wall-distance region inside the boundary layer, and that the size of this region is larger for the shorter beam. The interaction of a flexible piezoelectric beam with vortex rings was another topic investigated. Time-resolved PIV images were taken synchronously with strain, base-force and piezoelectric voltage data as a vortex ring travels over a piezoelectric beam. The dynamic tip deflection of the beam estimated using the PIV data in a potential flow solution was found comparable to the measured tip deflection. In addition to the experimental work, a computational framework for modeling aeroelectromechanical interactions was developed by integrating an electrical circuit analysis code to a flow simulation program through external scripting. The framework was applied for the case of a flexible piezoelectric beam in the wake of a cylinder. A reasonable agreement was obtained between the computer simulations and the experimental results.

  • Of home and other figments: The passage of exile in the Tibetan diaspora

    Author:
    Sean Akerman
    Year of Dissertation:
    2011
    Program:
    Psychology
    Advisor:
    Suzanne Ouellette
    Abstract:

    This dissertation used a study of lives approach to understand the stories told by four Tibetans who came to New York following the passage of the Immigration Act of 1990 when Tibetans first came to the United States in mass. Not unlike other diasporas in the world today, the transfer of the events, the stories, and in many cases, the wounds, of exile formatively shape the narrative hereafter of younger generations, though this phenomenon has been given little attention in the social sciences. This work asked: 1) What stories of exile are passed from one generation to another and what are the mechanisms of transmission within that passage? (2) How is home understood generationally? (3) And within the experience of exile, what are the possibilities for action in daily life? Looking across four life historical accounts, my analysis revealed that the stories my informants heard as they grew up can be grouped into the themes of death, survival, and hope. The stories they passed on to younger people in their lives took the form of bodily care, solitude, and discrimination. These stories moved through the narrative mechanisms of translation, silence, and interlocutory slippage with attention to a story's didactic, shaping features. Home was understood as an impossibility for those younger Tibetans with whom I spoke, whereas it was associated with death and decay for older Tibetans. However, generational differences were downplayed by considering exile as a noun (a status) and verb (the ongoing result of an event), which was rife with socio-economic implications. Action took the form of community involvement and its gesture, a commitment to education, and a cursory knowledge of politics. These forms of action were narrated through bearing witness, employing the subjunctive, and calling attention to the body to narrate what escaped words. This inquiry highlights the importance of stories in the experience of exile, as well as the mechanisms through which exile is narrated. Additionally, my analysis emphasizes a consideration of death and natality as central to the experience of exile, and explores the literal and metaphorical ways through which death and natality become narrative forces.

  • CRISIS, FORMULATION AND AUTOBIOGRAPHICAL INTIMACY IN 1950s AMERICA

    Author:
    Olga Aksakalova
    Year of Dissertation:
    2012
    Program:
    English
    Advisor:
    Nancy Miller
    Abstract:

    Crisis, Formulation, and Autobiographical Intimacy in 1950s America explores how critical circumstances of historical and personal significance can inspire and direct autobiographical production. I concentrate on Alfred Kazin's A Walker in the City (1951), Vladimir Nabokov's Speak, Memory (1967), and Robert Lowell's Life Studies (1959), three American autobiographies whose first or final versions were produced in the nineteen fifties, decade marked by a surge of autobiographical texts and genres in the United States and the emergence of autobiographical theory in France. Engaging with Robert Jay Lifton's theory of trauma, namely the concept of formulation, I investigate how the relationship between the self and the world is fostered in the wake of a crisis as reflected in autobiographical performance unfolding through drafting, meta-writing, revision, publication, and republication. As I trace the evolution of the texts, I find each author's persistent attempt to forge a connection to the multiple relational others, including the reader, implicated in the autobiographical act. I argue that the prospect and process of gaining this connection - at once troubling and rewarding - tend to stimulate writing and facilitate revision as the writers cross the threshold from the pre-war to the post-war world and grapple with the shifts occurring in their private lives. In the course of writing and re-writing their autobiographies, Kazin, Nabokov, and Lowell develop a special kind of closeness with their relational others that arises from the interrelated acts of identification, projection, and narration. Looking at autobiographical process (revision, textual versioning) rather than merely product (final text), I illustrate how these acts are enhanced, qualified, or reversed as they are repeated. They produce autobiographical intimacy: forged by various forms of interaction(s), it is a virtual space whereby participants of the autobiographical act foster communication, reciprocity, and potentially trust - productively or otherwise.