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Beyond Darwin: Evolvability and the Generation of Novelty Marc Kirschner
Kirschner M BMC Biology 2013, 11:110 http://www.biomedcentral.com/1741-7007/11/110 INTERVIEW Open Access Beyond Darwin: evolvability and the generation of novelty Marc Kirschner Marc Kirschner graduated in biochemistry from North- western University, moving to Berkeley for his doctoral research and with positions at Berkeley, Oxford Univer- sity and Princeton before he took a professorship at Uni- versity of California San Francisco where with Andrew Murray he did seminal research on the control of the cell cycle in Xenopus egg extracts that led to the discov- ery of how cyclin drives the cell cycle, and with Tim Mitchison on the dynamic instability of microtubules. In 1993 he moved to Harvard where in 2003 he became the founding Chair of the HMS Department of Systems Biology and was named the John Franklin Enders Uni- versity Professor in 2009. The two books he wrote with John Gerhart, Cells, Embryos and Evolution (Blackwell, 1997) and The Plausibility of Life: Resolving Darwin’sDi- lemma (Yale University Press, 2005), reflect his deep and longstanding interest in how biological systems evolve. Here he gives his view of the evolution of evolvability and its profound importance for understanding and ap- plying biology. What is evolvability - how would you define it? Marc Kirschner In some sort of tautological way evolvability is simply the capacity of a system to evolve. But more than that, in a Darwinian sense it speaks to both the amount of effectively what I mean is that if you make random variation that is subject to selection, and the nature of changes in mechanical systems they inevitably either that variation. -
The Foreign Service Journal, January 1951
gL AMERICAN FOREIGN SERVICE JOURNAL JANUARY, 1951 .. .it’s always a measure warn ,0? KENTUCKY STRAIGHT BOUHBOI WHISKEY W/A BOTTLED IN BOND KENTUCKY BOURBON KENTUCKY STRAIGHT BOURBON WHISKEY • TOO PROOF • I. W. HARPER DISTILLING COMPANY, KENTUCKY REGISTERED DISTILLERY NO. 1, LOUISVILLE, KENTUCKY AMERICAN FOREIGN SERVICE ASSOCIATION HONORARY PRESIDENT FOREIGN SERVICE DEAN ACHESON SECRETARY OF STATE HONORARY VICE-PRESIDENTS THE UNDER SECRETARY OF STATE THE ASSISTANT SECRETARIES OF JOURNAL STATE THE COUNSELOR H. FREEMAN MATTHEWS PRESIDENT FLETCHER WARREN VICE PRESIDENT BARBARA P. CHALMERS EXECUTIVE SECRETARY EXECUTIVE COMMITTEE HERVE J. L.HEUREUX CHAIRMAN HOMER M. BYINGTON, JR. VICE CHAIRMAN WILLIAM O. BOSWELL SECRETARY-TREASURER DALLAS M. COORS ASSISTANT SECRETARY-TREASURER CECIL B. LYON ALTERNATES THOMAS C. MANN EILEEN R. DONOVAN STUART W. ROCKWELL PUBLISHED MONTHLY BY U. ALEXIS JOHNSON ANCEL N. TAYLOR THE AMERICAN FOREIGN SERVICE ASSOCIATION JOURNAL EDITORIAL BOARD JOHN M. ALLISON CHAIRMAN FRANK S. HOPKINS G. FREDERICK REINHARDT VOL, 28, NO. 1 JANUARY, 1951 WILLIAM J. HANDLEY CORNELIUS J. DWYER JOHN K. EMM FRSON AVERY F. PETERSON COVER PICTURE: A snowstorm blankets old Jerusalem. DAVID H. MCKILLOP Photo by FSO William C. Burdett, Jr. JOAN DAViD MANAGING EDITOR ROBERT M. WINFREE REGIONAL CONFERENCES IN 1950 13 ADVERTISING MANAGER By Alfred H. Lovell, FSO EDUCATION COMMITTEE REGIONAL CONFERENCE AT THE HAGUE 16 G. LEWIS JONES CHAIRMAN By Thomas S. Estes, FSO H. GARDNER AINSWORTH MRS. JOHN K. EMMERSON MRS. ARTHUR B. EMMONS III WHAT! NO SPECIALISTS? 18 JOSEPH N. GREENE. JR. By Thomas A. Goldman, FSO J. GRAHAM PARSONS MRS. JACK D. NEAL THE UNITED NATIONS AND THE FORMER ITALIAN COLONIES 2C ENTERTAINMENT COMMITTEE By David W. -
The Drosophila MCPH1-B Isoform Is a Substrate of the APC E3 Ubiquitin Ligase Complex
ß 2014. Published by The Company of Biologists Ltd | Biology Open (2014) 3, 669–676 doi:10.1242/bio.20148318 RESEARCH ARTICLE The Drosophila MCPH1-B isoform is a substrate of the APCCdh1 E3 ubiquitin ligase complex Sarah G. Hainline`, Jamie L. Rickmyre`,*, Leif R. Neitzel, Laura A. Lee§ and Ethan Lee§ ABSTRACT and two primary co-activators, Cdc20 and Cdh1 (Kulkarni et al., 2013). Destruction of APC substrates is required in eukaryotes for The Anaphase-Promoting Complex (APC) is a multi-subunit E3 the initiation of anaphase and exit from mitosis. Cdc20 associates ubiquitin ligase that coordinates progression through the cell cycle by with the APC in early mitosis, leading to the destruction of temporally and spatially promoting the degradation of key proteins. proteins that control the onset of anaphase, whereas Cdh1 Many of these targeted proteins have been shown to play important promotes degradation of APC substrates that control late mitosis roles in regulating orderly progression through the cell cycle. Using and the following G1 phase. These co-activators provide APC a previously described Drosophila in vitro expression cloning substrate specificity by facilitating the recognition of specific approach, we screened for new substrates of the APC in Xenopus destruction motifs (e.g. degrons) such as the D-box (RxxLxxxxN) egg extract and identified Drosophila MCPH1 (dMCPH1), a protein or KEN box (Lys–Glu–Asn) (King et al., 1996; Min and Lindon, encoded by the homolog of a causative gene for autosomal recessive 2012; Pfleger and Kirschner, 2000). Mutations of these motifs primary microcephaly in humans. The dMCPH1-B splice form, but not block the recognition of the protein by the APC, preventing their the dMCPH1-C splice form, undergoes robust degradation in APC-mediated destruction. -
TWAS 27Th General Meeting - Kigali, Rwanda, 14-17 November 2016 List of Participants
TWAS 27th General Meeting - Kigali, Rwanda, 14-17 November 2016 List of Participants 1 Samir ABBES 9 Sabah ALMOMIN (FTWAS) 18 Marlene BENCHIMOL Associate Professor Research Scientist Brazilian Academy of Sciences Higher Institute of Biotechnology of Beja Biotechnology Department Rio de Janeiro (ISBB) Kuwait Institute for Scientific Research Brazil Habib Bourguiba Street (KISR) BP: 382; Beja 9000 P.O. Box 24885 University of Jendouba Safat 13109 19 Tonya BLOWERS Jendouba 8189 Kuwait OWSD Programme Coordinator Tunisia Organization for Women in Science for 10 Ashima ANAND (FTWAS) the Developing World (OWSD) 2 Ahmed E. ABDEL MONEIM Principal Investigator c/o TWAS, ICTP Campus Lecturer Exertional Breathlessness Studies Strada Costiera 11 Zoology and Entomology Department Laboratory 34151 Trieste Faculty of Science Vallabhbhai Patel Chest Institute Italy Helwan University P.O. Box 2101 11795 Ain Helwan Delhi University 20 Rodrigo de Moraes BRINDEIRO Cairo Delhi 110 007 Director Egypt India Institute of Biology Federal University of Rio de Janeiro 3 Adejuwon Adewale ADENEYE 11 Asfawossen ASRAT KASSAYE (UFRJ) Associate Professor Associate Professor Rio de Janeiro Department of Pharmacology School of Earth Sciences Brazil Faculty of Basic Medical Sciences Addis Ababa University Lagos State University College of P.O. BOX 1176 21 Federico BROWN Medicine Addis Ababa Assistant Professor 1-5 Oba Akinjobi Way Ethiopia Departamento de Zoologia G.R.A. Ikeja, Lagos State, Nigeria Instituto de Biociências 12 Thomas AUF DER HEYDE Universidade de São Paulo 4 Ahmed A. AL-AMIERY Deputy Director General Rua do Matão, Travessa 14, n.101 Assistant Professor Ministry of Science and Technology Cidade Universitária Environmental Research Center Department of Science and Technology São Paulo SP. -
Deptbiochemistry00ruttrich.Pdf
'Berkeley University o'f California Regional Oral History Office UCSF Oral History Program The Bancroft Library Department of the History of Health Sciences University of California, Berkeley University of California, San Francisco The UCSF Oral History Program and The Program in the History of the Biological Sciences and Biotechnology William J. Rutter, Ph.D. THE DEPARTMENT OF BIOCHEMISTRY AND THE MOLECULAR APPROACH TO BIOMEDICINE AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO VOLUME I With an Introduction by Lloyd H. Smith, Jr., M.D. Interviews by Sally Smith Hughes, Ph.D. in 1992 Copyright O 1998 by the Regents of the University of California Since 1954 the Regional Oral History Office has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the Nation. Oral history is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well- informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is indexed, bound with photographs and illustrative materials, and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable. -
Coups, Corporations, and Classified Information∗
COUPS, CORPORATIONS, AND CLASSIFIED INFORMATION∗ ARINDRAJIT DUBE ETHAN KAPLAN SURESH NAIDU We estimate the impact of coups and top-secret coup authorizations on asset prices of partially nationalized multinational companies that stood to benefit from US-backed coups. Stock returns of highly exposed firms reacted to coup authorizations classified as top-secret. The average cumulative abnormal return to a coup authorization was 9% over 4 days for a fully nationalized company, rising to more than 13% over sixteen days. Pre-coup authorizations accounted for a larger share of stock price increases than the actual coup events themselves. ∗We would like to thank Martin Berlin, Remeike Forbes, Nathan Lane, Zihe Liu, Ettore Panetti, Andre Shepley, and Laurence Wilse-Samson for excellent research assistance. Frans Buelens helped us greatly in obtaining data. Noel Maurer shared his list of U.S. multinational expropriations with us. Oliver Boguth provided us historical data on three Fama-French factors. Marcos Chamon, Stefano DellaVigna, Ray Fisman, Eric Freeman, David Gibbs, Lena Nekby, Torsten Persson, John Prados, Gerard Roland, and seminar participants at CEMFI, Hampshire College, LSE, IIES, NBER Political Economy Summer Institute, the New School, NYU, the Santa Fe Institute, the Stockholm U. Economics Department, the Stockholm School of Economics, UC Berkeley, UC Riverside, the U. of Michigan at Ann Arbor, the U. of Oslo, and the U. of Warwick all provided helpful comments. 1 There is no effect in the case of the widely publicized, poorly executed Cuban operations, consistent with abnormal returns to coup authorizations reflecting credible private information. We also introduce two new intuitive and easy to implement nonparametric tests that do not rely on asymptotic justifications. -
A Thesis Entitled a Socio-Historical Analysis of U.S. State Terrorism
A Thesis Entitled A Socio-Historical Analysis of U.S. State Terrorism from 1948 to 2008 By Chad A. Malone Submitted as partial fulfillment of the requirements for The Master of Arts in Sociology ___________________________________ Advisor: Dr. Elias Nigem ___________________________________ Committee Member: Dr. Dwight Haase ___________________________________ Committee Member: Dr. Marietta Morrissey ___________________________________ College of Graduate Studies The University of Toledo August 2008 An Abstract of A Socio-Historical Analysis of U.S. State Terrorism from 1948 to 2008 Chad A. Malone Submitted as partial fulfillment of the requirements for The Master of Arts in Sociology The University of Toledo August 2008 This thesis is a critical examination of U.S. foreign intervention from 1948 to 2008. Using a comparative/historical analysis of seven cases—Iran, Guatemala, Indonesia, Chile, Nicaragua, Panama, and Iraq—this study finds patterns of U.S. state/state-sponsored terror and intervention. Using world-system theory and G. William Domhoff’s class-domination theory of power, this study explains how and why the U.S. government, the U.S. military, the CIA, and U.S. corporations participate in economically motivated terrorist acts to support the capitalist mode of production, U.S. investments, and access to markets and natural resources. Finally, this study reveals patterns (in addition to the use of terror) that the U.S. government follows while intervening in the affairs of foreign nations. ii Dedication This thesis is dedicated to my parents. While they may not always agree with what I say or write, they have always been supportive of my education and my goals. -
G ATEMALA by Helen Simon Travis and A
THE TRUTH ABOUT G ATEMALA By Helen Simon Travis and A. B. Magil About the Authors HELEN SIMON TRAVIS visited Guatemala in 1953, where she interviewed outstanding government, trade union, peasant, and cultural leaders. Her stirring report on developments in that country is based on eye-witness observation. A. B. MAGIL visited -Guatemala in 1951 and again in 1954. He is the author 'of numerous books and pamphlets, and is widely known as a writer, lecturer, and educator. He is pres ently associate editor of Masses & Mainstream. The drawing on the cover of this pamphlet is from a poster by the distinguished Mexican artist, Alberto Beltran. The quetzal bird is the national symbol of Guatemala. Published by NEW CENTURY PUBLISHERS, 832 Broadway, New York 3, N. Y. April, 1954 PRINTED IN THE U.S.A. ~. 209 By HELEN SIMON TRAVIS and A. B. MAGIL- It was Sunday, March 29, 1953. Two hundred men donned their new uniforms, grabbed their new rilles, grenades, ma chine-guns. Swiftly they descended on the town of Salama, a provincial capital not far from Guatemala City. They seized the mayor, others, representing the democratic authority of the state. They cut telephone and telegraph lines. Then they awaited news of other successful uprisings throughout this isolated democratic Central American republic. But the ne~Ts never came. l<t had spent a quiet, sunshiny Sunday in the country. I only learned about Salama the next day, and then it was all over. The 200 held on for 12 hours, but no masses flocked to their anti-democratic banners. -
Interpretation: Hemichordates May Have No “Notochord”
iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 3 Part 3. How did the Chordate get its chord (notochord)? Marc Kirschner Dept. of Systems Biology Harvard Medical School Boston Massachusetts The Spemann experiment and the vertebrate specific development What about the notochord? Interpretation: Hemichordates • The crux of Bateson’s argument that hemichordates were essentially chordates. may have no “notochord”. • Virtually every marker of the vertebrate notochord is present in the hemichordate (chordin, noggin, admp, brachyury, hedgehog….) • Small problem, they are not in the hemichordate stromachord. The American Society for Cell Biology 1 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 3 But does it have a Spemann Organizer? Though the organizer gives rise to the notochord in vertebrates, it is in fact also a complex signaling center. The hemichordate expresses genes of the chordate prechordal endo-mesoderm (otx, dmbx, ttf2, hex, gsc…), and at the appropriate A/P map position. ttf2/foxE2 dmbx Interpretation: as a signaling center, the hemichordate has an organizer otx The vertebrate organizer is a tripartite structure of signaling centers The American Society for Cell Biology 2 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 3 But these organizer signaling centers are initially dispersed in hemichordates The vertebrate organizer is a composit of three distinct signaling centers in hemichordates • The vertebrate organizer is complex, since it conflates dorsal/ventral -
Iaj 8-4 (2017)
A Brief History of Scandals: Special Oversight Challenges in National Security Interrogations Erik Jens A CGSC International Hall of Fame Member and the CIA’s Covert Action in 1954 John G. Breen Application of the Ethical Triangle in the 2014 Ebola Epidemic: A Case Study Katie Martinez and Marcos Martinez Why We Keep Getting it Wrong: What Makes the JIIM so Different? William J. Davis, Jr. The Vision Process: Seven Steps to a Better Organization Matthew J. Bonnot and Carey W. Walker Speak Smartly and Carry a Big Stick: Competing Successfully in the Global Narrative Brian Anthony, Robert Lyons and Stuart Peebles Train with the Brain in Mind: Neuroscience Education as a Force Multiplier Michael J. Cheatham Decline of Westphalia in West Africa: How Decentralized Power in West Africa The Journal of The Simons Center Can be a Rebirth of African Identity Vol. 8, Issue 4 (2017) Matthew D. Pride, Bryan C. Smith Arthur D. Simons Center for Interagency Cooperation, Fort Leavenworth, Kansas FEATURES | 1 and Harmonie Foster About The Simons Center The Arthur D. Simons Center for Interagency Cooperation is a major program of the Command and General Staff College Foundation, Inc. The Simons Center is committed to the development of military leaders with interagency operational skills and an interagency body of knowledge that facilitates broader and more effective cooperation and policy implementation. About the CGSC Foundation The Command and General Staff College Foundation, Inc., was established on December 28, 2005 as a tax-exempt, non-profit educational foundation that provides resources and support to the U.S. Army Command and General Staff College in the development of tomorrow’s military leaders. -
The Invention of Courts the Unstable Biomedical Research Ecosystem
american academy of arts & sciences spring 2015 www.amacad.org vol. lxviii, no. 3 american academy of arts & sciences bulletin spring 2015 Bulletin Academy Report Explores the State of the Humanities in Higher Education The Invention of Courts Jamal Greene, Carol S. Steiker, Susan S. Silbey, Linda Greenhouse, Jonathan Lippman, and Judith Resnik The Unstable Biomedical Research Ecosystem: How Can It Be Made More Robust? Mark C. Fishman, Nancy C. Andrews, Sally Kornbluth, Susan R. Wente, Richard H. Brodhead, Harold Varmus, and Tania Baker ALSO: Replenishing the Innovation Pipeline: The Role of University Research Mr g–The Story of Creation as Told by God Policy Perspective on the Police Use of Lethal Force On the Professions In Memoriam: David Frohnmayer Upcoming Events JUNE NOVEMBER 15th 17th Washington, DC Cambridge, MA The Ritz-Carlton Georgetown House of the Academy Reception for Washington, DC, Chamber Series Area Fellows and Guests in collaboration with the Welcome Newly Elected Fellows Cantata Singers Made in America: Songs by Barber, OCTOBER Copland, and Fine 9th–11th Cambridge, MA Induction Weekend 9th A Celebration of the Arts and Humanities 10th Induction Ceremony 11th Academic Symposium For updates and additions to the calendar, visit www.amacad.org. Special Thanks e recently completed another successful fund-raising year with more than W$6.7 million raised. The Annual Fund surpassed $1.7 million, a record-break- ing total. Gifts from all other sources–including grants for projects–totaled more than $5 million. We are grateful for the generosity of an increasing number of contributors–including members, staff, and friends; foundations, corporations, and associations; and Univer- sity Affiliates–who made these results possible. -
Ibioseminars: Marc Kirschner, March 2008 the Origin of Vertebrates, Part 2 the American Society for Cell Biology 1
iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 Part 2. Telling the back from the front or what the chordates invented Marc Kirschner Dept. of Systems Biology Harvard Medical School Boston Massachusetts The position of the CNS has been used to define the body plan of organisms But what does that say for an organism that has a clear D/V axis but no centralized nervous system? The American Society for Cell Biology 1 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 Using the standard convention call the mouth, ventral Dorsal Mouth Ventral BMP, a form of TGF-β, is involved in D/V patterning BMP and anti-BMP (chordin, sog) are conserved in neural specification in flies and frogs What role do they have in hemichordates which have no CNS? The American Society for Cell Biology 2 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 The genes that are patterned by BMP in the vertebrate neural tube are not conserved in Saccoglossus Shh responsive bmp responsive Yet, every detail of the BMP gradient seems fundamental to D/V patterning What is the BMP pathway being used for? The American Society for Cell Biology 3 iBioSeminars: Marc Kirschner, March 2008 The Origin of Vertebrates, Part 2 siRNA is a powerful tool in for answering such questions So radialized the dorsal structure that holds the proboscis to the collar doesn’t form Knockdown of BMP causes ventral radialized embryos and the proboscis falls off. Increased BMP dorsalizes The American Society for Cell Biology 4 iBioSeminars: