VictorJuiz/thesis huggingface dataset:
The role of epidermal growth factor receptor in autoimmune arthritis [electronic resource]

Rheumatoid arthritis (RA) is an autoimmune synovitis affecting approximately 0.5% of the population worldwide. In addition to T cells, B cells and macrophages, cells such as synovial fibroblasts promote inflammation in the synovium by producing cytokines and chemokines. At the same time, neovascularization provides nutrients and oxygen to the growing pannus and increased osteoclastogenesis causes bone destruction. RA serum and synovial fluid contains increased concentrations of epidermal growth factor receptor (EGFR) ligands; and synovial fibroblasts and endothelial cells in RA synovium express EGFR. Thus, we hypothesized that a specific EGFR tyrosine kinase inhibitor, erlotinib, would ameliorate murine collagen-induced arthritis (CIA). Erlotinib is currently prescribed for the treatment of non-small cell lung cancer and pancreatic cancer. Here, we demonstrate that erlotinib reduces the severity of established murine CIA and investigated the mechanisms of this inhibition. Erlotinib reduced: 1) EGF-induced proliferation of fibroblasts and human umbilical vein endothelial cells (HUVEC), 2) EGF-induced production of IL-8 and vascular endothelial cell growth factor (VEGF) by fibroblasts, and 3) the development of osteoclasts from bone marrow cells. Together, these findings suggest that EGFR plays a central role in the pathogenesis of RA and that EGFR inhibition may provide benefit in the treatment of RA.

Advisor: Robinson William (William Hewitt) primary advisor. Thesis advisor
Fathman C. Garrison
Sobel Raymond (Raymond A.)
Steinman Lawrence advisor. Thesis advisor
The role of molecular elasticity in biopolymers and protein self-assembly [electronic resource]

Molecular structure of many polymers including biopolymers creates elastic rigidity that impacts polymers behavior. Understanding this impact is critical to address the physics describing variety of single-molecule experiments and biological processes. Utilizing analytical theories and numerical methods, we illustrate the effect of molecular elasticity on the behavior of single molecules employed in single-molecule experiments as well as the morphology of assemblages in protein self-assembly processes. Single-molecule experiments are employed to characterize thermodynamics and kinetics of biomolecules such as DNA and RNA during biomolecular processes. In these experiments, we address the effect of thermal fluctuation, focusing on the equilibrium statistical behavior of specific class of underling single molecules, which act as semiflexible polymers, to gain insight into the physics governing their behavior. To demonstrate the role that molecular elasticity plays in protein self-assembly processes, we focus on clathrin protein, a protein recruited by the cell wall for ingesting food particles during endocytosis. We demonstrate that molecular elasticity and binding affinity have a significant impact on the versatile equilibrium and non-equilibrium assemblages occurred in clathrin protein self-assemby process. These results are essential in guiding experiments utilizing clathrin proteins in biotemplating for self-assembly of nanostructures.

Keywords: Mechanical Engineering
Advisor: Spakowitz Andrew James primary advisor. Thesis advisor
Doniach S. advisor. Thesis advisor
Heilshorn Sarah advisor. Thesis advisor
Shaqfeh Eric S. G. (Eric Stefan Garrido) advisor. Thesis advisor
Role of p19ARF in MYC inactivation induced senescence and sustained tumor regression and generation of inducible BMI1 transgenic model [electronic resource]

MYC oncogene overexpression leads to rapid induction of tumors in animal models. We have previously shown that inactivation of MYC in tumors causes tumor regression. We identified senescence as a critical mechanism of MYC inactivation induced sustained tumor regression. This is the first time oncogene inactivation induced, in contrast to oncogene induced, senescence is reported. Here, we show that tumor suppressors p16INK4A, pRB and p19ARF are required for induction of senescence as well as sustained tumor regression. Either knockout of p53 or p19ARF accelerated MYC induced lymphomas and resulted in a dramatic increase in the incidence of tumor recurrence. Neither loss of p19ARF or p53 prevented proliferative arrest or apoptosis upon MYC inactivation. Loss of p19ARF, but not p53, was associated with a strong inhibition of senescence upon MYC inactivation. We conclude that p19ARF is essential for MYC inactivation to elicit sustained tumor regression through the induction of senescence. We also provide evidence that p19ARF mediates its effect on senescence in a p53 independent manner. We have uncovered that, in the absence of p19ARF, MYC inactivation in lymphomas leads to strong upregulation of NANOG, POU5F1, SOX2, GATA4, GATA6 and CCND1. Presence of either transgenic MYC or p19ARF represses the expression of these genes. Upregulation of self renewal associated genes NANOG, POU5F1 and SOX2 suggests that p19ARF null lymphomas may have expanded cancer stem cell fraction, which, in turn, could explain the propensity of p19ARF null lymphomas to reoccur. p16INK4A and p19ARF expression are regulated by BMI1. To study the role of BMI1 in cancer, senescence and stem cells, we generated a mouse model of conditional BMI1 overexpression. We present preliminary results in characterization of conditional BMI1 mouse. We compare tumors that are induced by MYC and by both MYC and BMI1. Mouse model of conditional BMI1 overexpression will be a useful tool in the study of cancer, senescence and stem cells.

Advisor: Felsher Dean (Dean Walton) primary advisor. Thesis advisor
Sweet-Cordero Eric primary advisor. Thesis advisor
Attardi Laura advisor. Thesis advisor
Oro Anthony
The role of price primacy in the decision-making process [electronic resource]

Price is a key factor in any consumer marketplace decision, but exposure to price information can take place at different stages of a transaction. In this dissertation, I examine the effects of early attention to price, or price primacy on the decision making process at the neural and behavioral level. In these experiments, the price of an item was shown to individuals before or after the item itself was revealed. Using functional magnetic resonance imaging (fMRI) I demonstrated that price primacy appears to alter the process by which price and product information are integrated to determine an item's value. The data supported a framework in which viewing products first caused them to be evaluated in accordance with the question "how much do I like this product?" In contrast, when viewing prices first, the evaluation process seemed to reflect the question "how much is this product worth?" Behavioral experiments were used to validate this theory as well as the specific predictions made by the patterns of neural activation found in the imaging task related to purchasing different product categories, such as hedonic or utilitarian items. In particular, I demonstrate that in the domain of bargains, by focusing individuals on monetary worth, price primacy can act to increase purchasing rates of utilitarian products.

Keywords: Business.
Advisor: Shiv Baba
Khan Uzma Aslam
Simonson Itamar advisor. Thesis advisor
The role of price primacy in the decision-making process [electronic resource]

Price is a key factor in any consumer marketplace decision, but exposure to price information can take place at different stages of a transaction. In this dissertation, I examine the effects of early attention to price, or price primacy on the decision making process at the neural and behavioral level. In these experiments, the price of an item was shown to individuals before or after the item itself was revealed. Using functional magnetic resonance imaging (fMRI) I demonstrated that price primacy appears to alter the process by which price and product information are integrated to determine an item's value. The data supported a framework in which viewing products first caused them to be evaluated in accordance with the question "how much do I like this product?" In contrast, when viewing prices first, the evaluation process seemed to reflect the question "how much is this product worth?" Behavioral experiments were used to validate this theory as well as the specific predictions made by the patterns of neural activation found in the imaging task related to purchasing different product categories, such as hedonic or utilitarian items. In particular, I demonstrate that in the domain of bargains, by focusing individuals on monetary worth, price primacy can act to increase purchasing rates of utilitarian products.

Advisor: Shiv Baba
Khan Uzma Aslam
Simonson Itamar advisor. Thesis advisor
The role of the PDGFR and c-FMS signaling pathways in autoimmune demyelination [electronic resource]

Multiple Sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system characterized by demyelination and variable axonal loss. Tyrosine kinases play a central role in the activation of signal transduction pathways and cellular responses that mediate the pathogenesis of MS. Imatinib mesylate (imatinib), sorafenib, and GW2580 are tyrosine kinase inhibitors (TKIs) developed to treat diverse types of cancers. This thesis demonstrates that Imatnib and Sorafenib, two PDGFR inhibitors and GW2580, a specific Fms inhibitor, can prevent and treat MOG-induced experimental autoimmune encephalomyelitis (EAE). My observations suggest that the c-Fms and PDGFR tyrosine kinase signaling pathways play a central role in the pathogenesis of EAE and MS. I believe that c-Fms primes macrophages to produce TNF and that PDGFR induces astrocytes to proliferate, which are cellular responses contributing to autoimmune demyelination in multiple sclerosis. Chapter 1 provides a general introduction to MS and EAE and the role different cell types of the immune system play in disease pathogenesis, paying particular attention to the role of macrophages and astrocytes. Chapter 2 describes in further detail the different functions mediated by MCSF in macrophages and how these are tied to the pathology of MS. In this chapter, the experiments performed to determine whether c-Fms inhibition using tyrosine kinase inhibitors could have an effect on pathogenic macrophage functions are described. Chapter 3 focuses on the immune functions of astrocytes, emphasizing those believed to be mediated by PDGFR signaling, and the experiments performed to test the effects of tyrosine kinase inhibitors on PDGFR-mediated astrocyte functions. Chapter 4 concludes with a discussion of the results and future directions for the use of tyrosine kinase inhibitors for the screening of potential targets involved in the pathogenesis of autoimmune diseases.

Advisor: Robinson William (William Hewitt) primary advisor. Thesis advisor
Fathman C. Garrison
Steinman Lawrence advisor. Thesis advisor
Utz Paul advisor. Thesis advisor
Roles for the human sirtuin SIRT7 in chromatin regulation and cancer [electronic resource]

Sirtuins are a conserved family of NAD+-dependent deacetylases that regulate diverse biological processes including genomic stability, metabolism, and aging. SIRT7 is a mammalian sirtuin whose enzymatic activity and physiologic functions have been unclear. Here I present work aimed at elucidating the biochemical, molecular, and cellular roles of human SIRT7. In Chapter 1, I report the discovery that SIRT7 possesses deacetylase activity specific for histone H3 acetylated at lysine 18 (H3K18Ac). In genome-wide binding studies, we find that SIRT7 associates with promoters of a specific set of gene targets, where it deacetylates H3K18Ac and promotes transcriptional repression. In Chapter 2, I discuss the identification of a novel SIRT7 interacting protein, the ETS transcription factor ELK4. Our work suggests that ELK4 plays an important role in defining the spectrum of SIRT7 target genes, by recruiting SIRT7 to a subset of promoters. In Chapter 3, I present our work establishing new functions for SIRT7 in cancer progression. Notably, selective hypoacetylation of H3K18Ac has recently been linked to oncogenic transformation, and in patients is associated with aggressive tumor phenotypes and poor prognosis. We find that deacetylation of H3K18Ac by SIRT7 is necessary for maintaining essential features of human cancer cells including anchorage independent growth and escape from contact inhibition. Moreover, SIRT7 is necessary for a global hypoacetylation of H3K18Ac associated with cellular transformation by viral oncoproteins. Finally, SIRT7 depletion markedly reduces the tumorigenicity of human cancer cell xenografts in mice. Together, this work establishes SIRT7 as the first known site-specific H3K18Ac deacetylase and demonstrates a pivotal role for SIRT7 in chromatin regulation, cellular transformation programs, and tumor formation in vivo.

Keywords: Biology.
Advisor: Gozani Or Pinchas primary advisor. Thesis advisor
Chua Katrin Faye advisor. Thesis advisor
Frydman Judith advisor. Thesis advisor
Romantic rebellion, romantic retreat [electronic resource] : music and "1968" in West Germany

West Germany numbers among the many countries for which the year "1968" symbolizes an era of social unrest. My dissertation presumes that the fraught sociopolitical climate of this time and place somehow reverberated in art music. I particularly focus on compositions written in the decade following 1968. These works -- by composers including Wolfgang Rihm, Wilhelm Killmayer, and Dieter Schnebel -- reinvigorate certain characteristics of nineteenth-century music. My dissertation presents two interpretations of how this "neo-romantic" music developed from both the music of the 1960s and the "1968" context -- a context known in Germany as the Studentenbewegung, or West German student protest movement. One interpretation, which already exists in German musicology, views this music as development as a retreat from the progressive aesthetic and social ideals that had prevailed in the previous decade. The other, which my study helps to establish, views the same music as a modified continuation of the very rebellion that had characterized the immediate past. Both interpretations draw upon specific musical examples, prose writings of composers, previous scholarship about music particularly and West German culture generally, as well as the roughly contemporaneous social and aesthetic theories of T.W. Adorno and Herbert Marcuse.

Keywords: Music
Advisor: Berger Karol
Rodin Jesse primary advisor. Thesis advisor
Ulman Erik
School reform and the arts of re-enchantment [electronic resource]

'Disenchantment' has been a consistent trope in sociology since Weber's appropriation of the term nearly a century ago. In this work I argue that, in contrast to the standard modernization story, organizations have long been subject to countervailing forces other than that that of rationalization. This has been especially true in schools, institutions that exist at the intersection of the logics of bureaucracy, democracy and expressive youth cultures. In this dissertation I identify a uniquely contemporary organizational response to these tensions, one I associate with the notion of 're-enchantment.' I use this term to refer to reforms that identify emotional and intellectual alienation as the primary institutional problems to be overcome and find a solution in the reinvigoration of organizational practices with imagination, creativity, and collaboration. The result is a genre of reform that accepts the logic of standardized and rationalized outcomes but attempts to transform the process of achieving these goals by 're-enchanting' organizational experience with a sense of connectedness and creativity. In this dissertation I discuss small school reform generally, and a particular instance of it at Mill Town high specifically, as examples of organizational re-enchantment. More than just introducing new practices or structures, small school reform entails an effort to reshape the tactic and practical modes of coordination, what I call ways of being. These are social conventions that allow actors to coordinate with each other and their environment in a way that is grounded in a shared practical understanding of the proper ordering of people and things. In contrast to standard account that locate the barrier to change in the minds of organizational actors, utilizing a mixed-methods approach I show that much of the failure of the reform at Mill Town was not the result of beliefs, attitudes or values of teachers, but rather concerned the complexity of changing culturally disposed, and intersubjectively sustained, modes of coordination in the organization.

Keywords: Education.
Advisor: McFarland Daniel (Daniel A.) primary advisor. Thesis advisor
Labaree David F.
Stevens Mitchell L. advisor. Thesis advisor
Search for large extra dimensions based on observations of neutron stars with the Fermi-LAT [electronic resource]

According to the Large Extra Dimensions (LED) model of Arkani-Hamed, Dimopoulos, and Dvali (ADD), in addition to the (3+1) observed space-time dimensions, there exist n gravity-only spatial dimensions. Due to the presence of the additional dimensions, the Planck scale of gravity should be brought down from 1E16 TeV to the TeV scale, near the electroweak scale, and thus solve the hierarchy problem. Based on the ADD theory, Kaluza-Klein (KK) gravitons, having masses of the order 100 MeV and lifetimes of the order of billions of years, are expected to be produced within supernova cores by nucleon-nucleon gravi-bremsstrahlung in the LED model. Once produced, they are predicted to be trapped by the gravitational potential of subsequently formed neutron stars (NS), and their decay is predicted to contribute to a measurable gamma-ray flux from NS. In this dissertation, refinements to past theoretical models are made, including modifications for the expected spectral energy distribution based on orbital motion of the gravitons, and NS surface magnetic field and age. n = 2,3, ..., 7 extra dimensions are considered. A sample of 6 gamma-ray faint NS sources not reported in the first Fermi gamma-ray source catalog that are good candidates are selected for this analysis, based on age, surface magnetic field, distance, and galactic latitude. Based on 11 months of data from Fermi -LAT, 95% CL upper limits on the size of extra dimensions R from each source are obtained, as well as 95% CL lower limits on the (n+4)-dimensional Planck scale M_D. In addition, the limits from all of the analyzed NSs have been combined statistically using two likelihood-based methods. The results indicate more stringent limits on LED than quoted previously from individual neutron star sources in gamma-rays. In addition, the results are more stringent than current collider limits, from the LHC, for n < 4. If the Planck scale is around a TeV, then for n = 2,3, the compactification topology of LED must be more complicated than a torus.

Keywords: Applied Physics
Advisor: Bloom E. (Elliott)
Kapitulnik Aharon primary advisor. Thesis advisor
Graham Peter (Peter Wickelgren) advisor. Thesis advisor
A search for spectral lines from WIMP annihilation in the milky way using the Fermi large area telescope [electronic resource]

The most popular class of dark matter candidates is the class of weakly-interacting massive particles (WIMPs). The Fermi Large Area Telescope has the possibility of indirectly detecting WIMPs by the flux from their annihilation/decay products. When a WIMP annihilates or decays directly into a photon gamma and another particle Y the photons are monochromatic. Detection of the resulting spectral line(s) would provide convincing evidence for particulate dark matter and could provide the WIMP mass. In the case of no detection, knowledge of the dark matter distribution can be used to place limits on the annihilation cross section and lifetime for the WIMP(s) to Y-gamma channel. We present the spectrum from 4.8 to 264 GeV and spectral line flux upper limits, obtained from a subset of this spectrum, from 7 to 200 GeV. The spatial region of the dataset covers a large portion of the sky, the high latitudes plus the Galactic Center. We report upper limits on the WIMP cross sections for annihilation to gamma-gamma and Z-gamma and lower limits on the WIMP lifetime for decay to gamma-neutrino. We discuss the implications of the spectrum and line flux limits for several dark matter models with optimistic branching ratios for photon channels.

Keywords: Physics
Advisor: Bloom E. (Elliott)
Allen Steven G.
Funk Stefan
The search for WIMP dark matter continuum Gamma-ray emission from dark matter satellites in the milky way using the Fermi LAT [electronic resource]

This thesis focuses on the search for unknown dark matter (DM) satellites in the Milky Way using the Fermi Large Area Space Telescope (LAT). The Fermi Gamma-ray Space Telescope (Fermi) is a next generation space observatory, which was successfully launched on June 11th, 2008. The LAT is the principal scientific instrument onboard. Its unprecedented angular resolution and sensitivity in the 100 MeV to > 300 GeV energy range makes it an excellent instrument for probing the sky for DM satellites. Current N-body simulations based on the Lambda-CDM cosmology model predict a large number of as yet unobserved DM satellites in our galaxy; some satellites are predicted to be extended sources (> 1deg extension) as seen by the LAT. Our work assumes that a significant component of DM is a Weakly Interacting Massive Particle (WIMP) in the 100 GeV mass range. The annihilation of WIMPs results in many high energy gamma rays that can be well measured by the LAT. The WIMP produced gamma-ray spectrum from the putative DM satellites is considerably harder than most astrophysical sources. Also, DM satellites have no astronomical counterparts in the X-ray and radio bands, and the emission has no time variability. My thesis will focus on a blind analysis in the search for unknown DM satellites using one year of LAT data, and setting constraints on some WIMP models based on the results of our analysis in which we find no candidates.

Keywords: Physics
Advisor: Bloom E. (Elliott)
Funk Stefan
Wechsler Risa H. (Risa Heyrman) advisor. Thesis advisor
Search strategies for new physics at the LHC [electronic resource]

The LHC is in the frontline of experimental searches for New Physics beyond the Standard Model of Particle Physics. Its power is accompanied by no smaller challenges in analyzing and interpreting its results. In this thesis I explore ways to parameterize new physics phenomena, design search strategies that are sensitive to them, and interpret experimental results in general new physics contexts. In particular, I discuss interpretations of the first ATLAS analysis for supersymmetry with 70/nb of integrated luminosity. I also carry a careful investigation of comprehensive search strategies for new physics with jets and missing energy signatures, and estimate the sensitivity bounds of the 7 TeV LHC to new colored particles decaying to jets and and a neutral particle that escapes detection. Finally, I discuss the implications of the recent LHC excesses hinting to a Higgs boson with mass in the range 142-147 GeV. If confirmed, this range for the Higgs mass will be an important evidence for Split Supersymmetry. I work out the phenomenological predictions of this scenario that will be tested in the very near future by a variety of experiments, including direct and indirect dark matter detection, EDM experiments searching for CP violation and the 7 TeV run of the LHC.

Keywords: Physics
Advisor: Kallosh Renata primary advisor. Thesis advisor
Wacker Jay primary advisor. Thesis advisor
Wechsler Risa H. (Risa Heyrman) advisor. Thesis advisor