Institution
Brown University
Education•Providence, Rhode Island, United States•
About: Brown University is a education organization based out in Providence, Rhode Island, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 35778 authors who have published 90896 publications receiving 4471489 citations. The organization is also known as: brown.edu & Brown.
Papers published on a yearly basis
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TL;DR: RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module and competitively disrupts the interaction between these kinases.
Abstract: Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK module.
833 citations
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McMaster University1, Copenhagen University Hospital2, King Saud bin Abdulaziz University for Health Sciences3, Albert Einstein College of Medicine4, University of Toronto5, Brown University6, Utrecht University7, NewYork–Presbyterian Hospital8, Peking Union Medical College Hospital9, Sunnybrook Health Sciences Centre10, University of Ulsan11, National Institutes of Health12, Imperial College London13, United Arab Emirates University14, Humanitas University15, St George’s University Hospitals NHS Foundation Trust16, Emory University Hospital17, University at Buffalo18, Baylor College of Medicine19, University of Milano-Bicocca20, King Abdulaziz Medical City21, King Saud Medical City22, The George Institute for Global Health23, University of Virginia24, University of Washington25
TL;DR: A panel of 36 experts from 12 countries issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19, and assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.
Abstract: BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
832 citations
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TL;DR: The data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway.
Abstract: Estrogen triggers rapid yet transient activation of the MAPKs, extracellular signal-regulated kinase (Erk)-1 and Erk-2. We have reported that this estrogen action requires the G protein-coupled receptor, GPR30, and occurs via Gbetagamma-subunit protein-dependent transactivation of the epidermal growth factor (EGF) receptor through the release of pro-heparan-bound EGF from the cell surface. Here we investigate the mechanism by which Erk-1/-2 activity is rapidly restored to basal levels after estrogen stimulation. Evidence is provided that attenuation of Erk-1/-2 activity by estrogen occurs via GPR30-dependent stimulation of adenylyl cyclase and cAMP-dependent signaling that results in Raf-1 inactivation. We show that 17beta-E2 represses EGF-induced activation of the Raf-to-Erk pathway in human breast carcinoma cells that express GPR30, including MCF-7 and SKBR3 cells which express both or neither, ER, respectively. MDA-MB-231 cells, which express ERbeta, but not ERalpha, and low levels of GPR30 protein, are unable to stimulate adenylyl cyclase or promote estrogen-mediated blockade of EGF-induced activation of Erk-1/-2. Pretreatment of MDA-MB-231 cells with cholera toxin, which ADP-ribosylates and activates Galphas subunit proteins, results in G protein-coupled receptor (GPCR)-independent adenylyl cyclase activity and suppression of EGF-induced Erk-1/-2 activity. Transfection of GPR30 into MDA-MB-231 cells restores their ability to stimulate adenylyl cyclase and attenuate EGF-induced activation of Erk-1/-2 by estrogen. Moreover, GPR30-dependent, cAMP-mediated attenuation of EGF-induced Erk-1/-2 activity was achieved by ER antagonists such as tamoxifen or ICI 182, 780; yet not by 17alpha-E2 or progesterone. Thus, our data delineate a novel mechanism, requiring GPR30 and estrogen, that acts to regulate Erk-1/-2 activity via an inhibitory signal mediated by cAMP. Coupled with our prior findings, these current data imply that estrogen balances Erk-1/-2 activity through a single GPCR via two distinct G protein-dependent signaling pathways that have opposing effects on the EGF receptor-to-MAPK pathway.
830 citations
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TL;DR: A review of recent theoretical and experimental works related to mechanics and mechanical properties of 2D materials can be found in this article, where the authors show that there is a continual growth of interest in the mechanics of other two-dimensional materials beyond graphene.
829 citations
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16 Jun 2012TL;DR: This paper performs crowd-sourced human studies to find a taxonomy of 102 discriminative attributes and builds the “SUN attribute database” on top of the diverse SUN categorical database, which has potential for use in high-level scene understanding and fine-grained scene recognition.
Abstract: In this paper we present the first large-scale scene attribute database. First, we perform crowd-sourced human studies to find a taxonomy of 102 discriminative attributes. Next, we build the “SUN attribute database” on top of the diverse SUN categorical database. Our attribute database spans more than 700 categories and 14,000 images and has potential for use in high-level scene understanding and fine-grained scene recognition. We use our dataset to train attribute classifiers and evaluate how well these relatively simple classifiers can recognize a variety of attributes related to materials, surface properties, lighting, functions and affordances, and spatial envelope properties.
829 citations
Authors
Showing all 36143 results
Name | H-index | Papers | Citations |
---|---|---|---|
Walter C. Willett | 334 | 2399 | 413322 |
Robert Langer | 281 | 2324 | 326306 |
Robert M. Califf | 196 | 1561 | 167961 |
Eric J. Topol | 193 | 1373 | 151025 |
Joan Massagué | 189 | 408 | 149951 |
Joseph Biederman | 179 | 1012 | 117440 |
Gonçalo R. Abecasis | 179 | 595 | 230323 |
James F. Sallis | 169 | 825 | 144836 |
Steven N. Blair | 165 | 879 | 132929 |
Charles M. Lieber | 165 | 521 | 132811 |
J. S. Lange | 160 | 2083 | 145919 |
Christopher J. O'Donnell | 159 | 869 | 126278 |
Charles M. Perou | 156 | 573 | 202951 |
David J. Mooney | 156 | 695 | 94172 |
Richard J. Davidson | 156 | 602 | 91414 |