318 research outputs found

    Estradiol regulation of leucine-rich repeat immunoglobulin-like domains protein 1 (LRIG 1) and roles of estrogen receptor in translational regulation in breast cancer cells

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    Among the first diagnostic tests performed upon finding a tumor in the breast is the determination of the expression of three proteins: the Estrogen Receptor α (ERα), the Progesterone Receptor (PR) and Heregulin 2 (HER2). The ER, though often considered responsible for driving tumor growth, is usually indicative of a good prognosis as ER-positive tumors are typically more indolent in nature and responsive to endocrine therapy. Long after estrogens were known to drive the growth of many breast tumors, the estrogen receptor was identified. The ER is a modular transcription factor known to regulate the expression of over a thousand genes in breast cancer cells. As a master regulator of transcription, ER can impact the transcription and subsequent expression of many proteins that ultimately determine the growth and invasiveness of a tumor. As a transcriptional regulator, activation of ER with its cognate ligand, estradiol, results in a cascade of changes beginning with chromatin remodeling of estradiol-regulated genes. In an attempt to identify ER-interacting proteins that aid in this chromatin unfolding activity, we performed a yeast two-hybrid screen using amino acids 420-534 of ERα as bait and identified Eukaryotic translation initiation factor 3 subunit F (eIF3f) as an interaction partner. Fluorescence microscopy suggests that in the presence of estradiol, the location of ERα-eIF3f changes. Though unclear if eIF3f, a translation factor, plays a role in chromatin unfolding, as a translation factor, we suggest that the interaction between eIF3f and ERα establishes a link through which estradiol can regulate translation. In support of this link, we find ERα in polysome profile fractions. Knockdown of eIF3f also appears to change the solubility of ERα within the nucleus. eIF3f knockdown also results in changes in steady-state mRNA levels of specific estradiol-target genes. Upon isolation of mRNA following polysome fractionation, we observe differences in the rate of translation of several estradiol-regulated mRNAs. Unlike other ERα-interacting partners such as Jab1 and E6-AP, eIF3f interacts with a shorter form of ERα. The effects of estradiol on cellular function are pleiotropic. As a transcriptional regulator, ER regulates many genes that can have a subsequent impact on other cellular functions. These so-called secondary effects are often associated as the principle actions of estradiol. We identify leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) as an estradiol-regulated gene. LRIG1 is a negative regulator of Receptor Tyrosine Kinase (RTK) signaling. Up-regulation of LRIG1 mRNA and protein is mediated by the estrogen receptor-α (ERα) and we identified the regions of the LRIG1 gene to which ER binds. LRIG1 regulation by estradiol helps to explain how tumors typically utilize either estradiol or growth factor pathways, but rarely both, as mitogenic stimuli. Increased LRIG1, in response to estradiol, results in decreased signaling through RTK pathways. The impact of LRIG1 regulation by estradiol is cell-type specific. LRIG1 protein levels are important for both the growth of cells as well as colony formation and invasiveness of ERα-positive and HER2-positive BT-474 and ERα-positive and HER2-negative MCF-7 breast cancer cell lines. LRIG1 regulation by estradiol may be important for breast cancer etiology and phenotypic properties by influencing signaling pathways such as the AKT and MAPK pathways, which help to determine the breast tumor subtype as well as responsiveness to cancer treatments.Item withdrawn by Mark Zulauf ([email protected]) on 2010-12-01T18:19:42Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Cory Funk Dissertation Final.pdf: 3730875 bytes, checksum: ac8357ae1f4b71a1d6bdcb02a12b860b (MD5)Made available in DSpace on 2011-01-21T22:53:12Z (GMT). No. of bitstreams: 2 Funk_Cory.pdf: 3730816 bytes, checksum: 9ca60cfa3f97f8f96172f9e8dd816218 (MD5) license.txt: 4059 bytes, checksum: 6775835502017b91316097e88ffee97f (MD5)Item marked as restricted to the 'Administrator' Group (id=1) by William Ingram ([email protected]) on 2011-01-21T22:54:08Z Item is restricted until 2013-01-21T22:53:34ZItem reinstated by Sarah Shreeves ([email protected]) on 2013-01-22T11:00:19Z Item was in collections: University of Illinois Dissertations and Theses (ID: 204) Dissertations and Theses - Cell and Developmental Biology (ID: 702) No. of bitstreams: 2 Funk_Cory.pdf: 3730816 bytes, checksum: 9ca60cfa3f97f8f96172f9e8dd816218 (MD5) license.txt: 4059 bytes, checksum: 6775835502017b91316097e88ffee97f (MD5)Item released from any restrictions by Sarah Shreeves ([email protected]) on 2013-01-22T11:00:19

    A Modern Approach and Analysis of the Electric Guitar in Funk, R&B, and Jazz Fusion

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    Within the contemporary and commercial music realm the electric guitar has been a driving force in the Funk genre since its inception and emergence from the late 1950s and early 1960s. Although the instrument has been given considerable attention in the style of Funk, there is far less information relative to its evolution and influence from the late twentieth to the twenty first century. The small number of publications on early Funk, R&B, and Jazz Fusion electric guitar has done little to highlight the guitarists discussed herein. The purpose of this report is to discuss the approach of guitarists Robben Ford, Mark Lettieri, Ole Børud, Cory Wong, KC Roberts, Tom McGuire, and their influence in contemporary Funk, R&B, and Jazz Fusion. The reader will acknowledge and form an understanding of the styles, techniques, and musicality these artists have contributed to the performance of contemporary guitar. By permeating a detailed background into their work, I will breakdown the history, theory, musical and harmonic analysis pertained to a total of nine songs that utilize a modern-day rhythm section with horns. The research, transcriptions, arrangements, analyses, and live recording session included herein will present, recognize, and conclusively prove why these musicians are both undervalued and among some of the most brilliant, virtuosic, and talented performers within the popular music realm of our time

    On the Truly Noncooperative Game of Island Life: Introducing a Unified Theory of Value & Evolutionarily Stable Island Economic Development Strategy

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    This discourse offers a solution to The Problem of Sustainable Economic Development on islands. This hypothesis offers a foundational, sub-game solution to The Island Survival Game, a counterintuitive, dominant economic development strategy for ‘islands’ (and relatively insular states). This discourse also tables conceptual building blocks, prerequisite analytical tools, and a guiding principle for The Earth Island Survival Game, a bounded delay supergame which models The Problem of Sustainable Economic Development at the global level. We begin our exploration with an introduction to The Principle of Relative Insularity, a postulate which informs ESS for ‘island’ and ‘continental’ players alike. Next, we model ‘island’ economic development with two bio-geo-politico-economic models and respective strategies: The Mustique Co. Development Plan, and The Prince Edward Island Federal-Provincial Program for Social and Economic Advancement. These diametrically opposed strategies offer an extraordinary comparative study. One island serves as a highly descriptive model for The Problem of Sustainable Economic Development; the other model informs ESS. The Island Survival Game serves as a remarkable learning tool, offering lessons which promote Darwinian fitness, resource holding power, self-sufficiency, and cooperative behaviour, by illuminating the illusive path toward sustainable economic development.Non-cooperative games, evolutionary game theory, relative insularity, islands, tragedy of the commons, sustainable economic development, resource holding power, evolutionarily stable strategy, long distance dispersal

    On the Problem of Vague Terms: A Glossary of Clearly Stated Assumptions & Careful, Patient, Descriptions

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    Coase 1930 endures through the decades as one of the most-cited papers in economics due to the fact that it highlights a fundamental and equally enduring problem: "Economic theory has suffered in the past from a failure to state clearly its assumptions. Economists in building up a theory have often omitted to examine the foundations on which it was erected. This examination is, however, essential not only to prevent the misunderstanding and needless controversy which arise from a lack of knowledge of the assumptions on which a theory is based, but also because of the extreme importance for economics of good judgement in choosing between rival sets of assumptions." In 1944 Von Neumann and Morgenstern offered the simply, yet invariably rejected solution: "In… economics the most fruitful work may be that of careful, patient description; indeed this may be by far the largest domain for the present and some time to come….Economic problems [have been and are often] not formulated clearly and are often stated in such vague terms as to make mathematical treatment a priori appear hopeless because it is quite uncertain what the problems really are. There is no point in using exact methods where there is no clarity in the concepts and issues to which they are to be applied. Consequently the initial task is to clarify the knowledge of the matter by further careful descriptive work." This paper offers a stone along the path to the solution to this problem by offering a glossary in this spirit, a glossary germain to some of the most fundamental, open problems in economics. As the fate of the human race may lay in the balance to finding solutions to these problems, this glossary may be a steop in the right direction.economic terms; methodology; scientific method; coase 1930; Von Neumann & Morgenstern 1944; definitions; careful, patient descriptions

    Estradiol Regulation of Leucine-Rich Repeat Immunoglobulinlike Domains Protein 1 (Lrig 1) and Roles of Estrogen Receptor in Translational Regulation in Breast Cancer Cells

    No full text
    The effects of estradiol on cellular function are pleiotropic. As a transcriptional regulator, ER regulates many genes that can have a subsequent impact on other cellular functions. These so-called secondary effects are often associated as the principle actions of estradiol. We identify leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) as an estradiol-regulated gene. LRIG1 is a negative regulator of Receptor Tyrosine Kinase (RTK) signaling. Up-regulation of LRIG1 mRNA and protein is mediated by the estrogen receptor-alpha (ERalpha) and we identified the regions of the LRIG1 gene to which ER binds. LRIG1 regulation by estradiol helps to explain how tumors typically utilize either estradiol or growth factor pathways, but rarely both, as mitogenic stimuli. Increased LRIG1, in response to estradiol, results in decreased signaling through RTK pathways. The impact of LRIG1 regulation by estradiol is cell-type specific. LRIG1 protein levels are important for both the growth of cells as well as colony formation and invasiveness of ERalpha-positive and HER2-positive BT-474 and ERalpha-positive and HER2-negative MCF-7 breast cancer cell lines. LRIG1 regulation by estradiol may be important for breast cancer etiology and phenotypic properties by influencing signaling pathways such as the AKT and MAPK pathways, which help to determine the breast tumor subtype as well as responsiveness to cancer treatments.Made available in DSpace on 2015-09-28T15:03:23Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3455717.pdf: 3830870 bytes, checksum: 3b3477fdfeb2cb5f7fdd1aac5974fb5c (MD5) Previous issue date: 2010Embargo set by: Seth Robbins for item 87611 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDsRestricted to the U of I community idenfinitely during batch ingest of legacy ETDsU of I Only111 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2010

    The classification of the Compositae: A tribute to Vicki Ann Funk (1947–2019)

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    The classification of the family Compositae (Asteraceae) has been much improved in the last decades by the application of molecular methods culminating in the recompilation published in 2009, Systematics, evolution, and biogeography of Compositae. Additional evidence of relationships has come from the use of high-throughput sequencing methods. Our late colleague Vicki Ann Funk (1947–2019) was a pioneer in this line of research. Together with her team, she contributed to the achievement of a mature classification of the family, which she left outlined. In this paper, we contribute this classification including all of the recent advances at the subtribal level and review in depth all contributions to Compositae classification made since the 2009 compilation.Abstract Introduction Material and methods Classification of Compositae Discussion and conclusions New infrafamilial taxa Author contribution

    Erratum: “Setup for meV-resolution inelastic X-ray scattering measurements and X-ray diffraction at the Matter in Extreme Conditions endstation at the Linac Coherent Light Source” (Review Of Scientific Instruments (2018) 89 (10F104) DOI: 10.1063/1.5039329)

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    In the original paper1 the co-author E. J. Gamboa was erroneously omitted. The corrected author list is identical to that of this erratum, and repeated below for clarity: E. E. McBride,1,2,a) T. G. White,3 A. Descamps,1,4 L. B. Fletcher,1 K. Appel,2 F. Condamine,5,6 C. B. Curry,1,7 F. Dallari,8 S. Funk,9 E. Galtier,1 E. J. Gamboa,1 M. Gauthier,1 S. Goede,2 J. B. Kim,1 H. J. Lee,1 B. K. Ofori-Okai,1,10 M. Oliver,11 A. Rigby,11 C. Schoenwaelder,1,9, P. Sun,1 Th. Tschentscher,2 B. B. L. Witte,1,12 U. Zastrau,2 G. Gregori,11 B. Nagler,1 J. Hastings,1 S. H. Glenzer,1 and G. Monaco8 1 SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, California 94025, USA 2 European XFEL GmbH, Holzkoppel 4, D-22869 Schenefeld, Germany 3 University of Nevada at Reno, Reno, Nevada 89506, USA 4 Department of Aeronautics and Astronautics, Stanford University, Stanford, California 94305, USA 5 Sorbonne Universits, UPMC, LULI, UMR 7605, Case 128, 4 Place Jussieu, 75252 Paris Cedex 05, France 6 LULI, Ecole Polytechnique, CEA-CNRS-UPS, 91228 Palaiseau, France 7 Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta T6G 1H9, Canada 8 Dipartimento di Fisica, Universit`a di Trento, via Sommarive 14, 38123 Povo, TN, Italy 9 Friedrich-Alexander-Universitat Erlangen-N ̈urnberg, Erlangen Centre for Astroparticle Physics, Erwin-Rommel-Str. 1, D-91058 Erlangen, Germany 10 Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA 11 Department of Physics, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom 12 Universit ̈at Rostock, Institut f ̈ur Physik, D-18051 Rostock, Germany

    Briefe über Merkwürdigkeiten der Litteratur /

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    Series of essays on modern literature (especially on Shakespeare and English literature) on the German language, and esthetics, with the exception of the last part written in the form of letters. The author of the majority of the letters is H. W. von Gerstenburg; the other contributors are P. Kleen, C. Fleisher and G. B. Funk. The introduction, by the editor, A. von Weilen, contains a brief history of the study of Shakespeare in the 18th century. Cf. [Einleitung], v. 2.[Einleitung] signed: Alexander von Weilen.v. 1. Erste und zweite Sammlung (Schleswig und Leipzig, 1766) -- v. 2. Dritte Sammlung (Schleswig und Leipzig, 1767) nebst Einleitung.Mode of access: Internet

    Systems modeling of metabolic dysregulation in neurodegenerative diseases

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    Neurodegenerative diseases (NDDs) encompass a wide range of conditions that arise due to progressive degeneration and ultimate loss of nerve cells in the brain and peripheral nervous system. NDDs such as Alzheimer’s, Parkinson’s and Huntington’s disease negatively impact both length and quality of life, without effective disease-modifying treatments. Herein, we review the use of genome-scale metabolic models, network-based approaches and integration with multi-omics data to identify key biological processes that characterize NDDs. We describe powerful systems biology approaches for modeling NDD pathophysiology by leveraging in silico models that are informed by patient-derived multi-omics data. These approaches can enable mechanistic insights into NDD-specific metabolic dysregulations that can be leveraged to identify potential metabolic markers of disease and pre-disease states

    Persistent inequality when learning requires a minimal standard of living

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    This paper studies the persistence of wealth and utility inequality in a dynamicmodel of skill acquisition with complete credit markets and rational, perfectly altruistic,dynastic utility-maximization, when efficient learning requires a minimal standardof living. The main result is that, if the minimal standard of living is not triviallysmall, at any stationary equilibrium without intergenerational mobility there are?poor?, unskilled and ?rich?, skilled dynasties. Members of rich dynasties inherit morefrom their parents than members of poor dynasties. The former in general acquireskill, while the latter remain unskilled, and - most importantly - members of rich familiesalso enjoy strictly higher utility than members of poor dynasties. This paper studies the persistence of wealth and utility inequality in a dynamicmodel of skill acquisition with complete credit markets and rational, perfectly altruistic,dynastic utility-maximization, when efficient learning requires a minimal standardof living. The main result is that, if the minimal standard of living is not triviallysmall, at any stationary equilibrium without intergenerational mobility there are?poor?, unskilled and ?rich?, skilled dynasties. Members of rich dynasties inherit morefrom their parents than members of poor dynasties. The former in general acquireskill, while the latter remain unskilled, and - most importantly - members of rich familiesalso enjoy strictly higher utility than members of poor dynasties
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