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Sample records for sir john adams

  1. Sir John Adams: his legacy to the world of particle accelerators

    CERN Document Server

    Wilson, E J N

    2011-01-01

    John Adams acquired an unrivalled reputation for his leading part in designing and constructing the Proton Synchrotron (PS) in CERN’s early days. In 1968, and after several years heading a fusion laboratory in the UK, he came back to Geneva to pilot the Super Proton Synchrotron (SPS) project to approval and then to direct its construction. By the time of his early death in 1984 he had built the two flagship proton accelerators at CERN and, during the second of his terms as Director-General, he laid the groundwork for the proton–antiproton collider which led to the discovery of the intermediate vector boson. How did someone without any formal academic qualification achieve this? What was the magic behind his leadership? The speaker, who worked many years alongside him, will discuss these questions and speculate on how Sir John Adams might have viewed today’s CERN.

  2. Sir John Adams - His Legacy to the World of Particle Accelerators

    CERN Multimedia

    CERN. Geneva

    2009-01-01

    John Adams acquired an unrivalled reputation for his leading part in designing and constructing the PS in CERN’s early days. In 1968, and after several years heading a fusion laboratory in the UK, he came back to Geneva to pilot the SPS project to approval and then to direct its construction. At the time of his untimely death in 1984 he had built Europe’s two largest proton accelerators at CERN. He went on, during the second of his terms as DG, to lay the groundwork for the proton-antiproton collider which led to the discovery of the intermediate vector boson. How did someone without any formal academic qualification achieve this? What was the magic behind his leadership? How did he achieve political success with the Member States of CERN in turning the almost hopeless quest for approval of the SPS to CERN’s advantage? How did he view his US counterpart, R. R. Wilson? The speaker, who worked many years alongside Adams, will discuss these questions and speculate on how Sir John Adams might have viewed t...

  3. Bookshelf. John Adams biography

    International Nuclear Information System (INIS)

    Billinge, Roy

    1993-01-01

    Full text: When John Bertram Adams died on 3 March 1984, CERN lost one of its principal architects. The late Sir John Adams was a very private person who rarely confided in his colleagues. This made the job of his biographer particularly difficult. Michael Crowley- Milling has succeeded admirably, and has performed a very important service. Is it a potted history of CERN, or the story of the building of the PS, or of the SPS? Yes, all of these, but most of all it is a thoughtful and discerning biography and a fitting tribute to a veritable giant of European science and technology. The sub-title,' Engineer Extraordinary' refers not only to John's outstanding ability as a builder of accelerators, but perhaps even more importantly, as a builder of teams and an 'engineer of opinions'. The book describes how John's attention to detail and intuitive engineering skills developed during the early part of his career, when working in radar research, and how he emerged as a natural leader in the building of the CERN PS. Then later, how his statesmanship enabled him to ''...rescue it (the 300 GeV Programme) from seeming political disaster and nurse it through technical problems to a successful conclusion.'' One crucial part of this process described is the visit to CERN in 1970 by Margaret Thatcher, at that time UK Secretary of State for Education and Science, and her subsequent letters of thanks, not only to Bernard Gregory as Director General, but also to John. It is interesting to speculate to what extent the good impression made on that occasion helped many years later, when as Prime Minister Mrs Thatcher decided that Britain should stay in CERN! After the successful commissioning of the SPS, the book goes on to describe the period when the two CERN Laboratories were merged under two Directors General. Unfortunately I found this part a little too low key, given that John and Leon van Hove presided over what was undoubtedly

  4. Sir John Meurig Thomas.

    Science.gov (United States)

    Thomas, John Meurig

    2013-10-11

    "My greatest achievement has been to combine being a teacher, a researcher, and a popularizer of science for over 50 years. My worst nightmare is to find myself dumbstruck when I am about to give a lecture …︁" This and more about Sir John Meurig Thomas can be found on page 10938. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. John Bertram Adams

    International Nuclear Information System (INIS)

    Stafford, G.H.

    1986-01-01

    This is the biography of a man obviously much liked and respected. It gives some personal details but is mainly concerned with his scientific work and achievements on major projects. Thus, some background information on those projects is also given as a context to the work of John Adams. The biography is written in sections; early years, the creation of CERN, Adams at CERN 1953-61, Adams and thermonuclear research 1958-69, (which includes his Directorship of the Culham Laboratory), Adams and the Ministry of Technology 1965-66, member for research of the UK Atomic Energy Authority 1966-69, Adams at CERN 1969-84 (as Director General of the SPS, as Executive Director-General of CERN 1979-81 and work at CERN up to 1984). (UK)

  6. John Adams Lecture

    CERN Multimedia

    PH Department

    2010-01-01

    13 December 2010 14:30 - Council Chamber, Bldg.503-1-001 Accelerator Breakthroughs, Achievements and Lessons from the Tevatron Collider V. Shiltsev / Fermilab’s Accelerator Physics Centre This year we celebrate the 25th anniversary of the first proton-antiproton collisions in the Tevatron. For two and a half decades the Tevatron at Fermilab (Batavia, IL, USA) was a centerpiece of the US and world’s High Energy Physics as the world’s highest energy particle collider at 1.8 TeV center of mass energy. While funding agencies are deciding on a 3-year extension of the Collider Run II operation through 2014, we – in this 2010 John Adams Lecture - will take a look in exciting story of the Tevatron: the story of long preparations, great expectations, numerous difficulties, years of “blood and sweat”, continuous upgrades, exceeding original goals (by a factor of 400) and high emotions. An accelerator scientist prospective will be given on a wide spectrum o...

  7. Thomas, Prof. Sir John Meurig

    Indian Academy of Sciences (India)

    Thomas, Prof. Sir John Meurig FRS. Date of birth: 15 December 1932. Address: Department of Materials Science and, Metallurgy, New Museums Site, 27, Babbage ... Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the Three Science Academies of India on the teaching of the theory of evolution more.

  8. John Adams and his times

    International Nuclear Information System (INIS)

    Amaldi, E.

    1986-01-01

    In this first John Adams' Memorial Lecture, an outline is given of his work, especially from the beginning of CERN in 1952 until his death in 1984. The historical survey covers John Adams' technical and managerial contributions to the development of CERN and its accelerators, as well as to fusion research in Britain and Europe. Exemplified by his role as member and president of the International Committee for Future Accelerators (ICFA), Adams' interest in international co-operation is also stressed. In the spirit of this great European, arguments are given for CERN to continue to be the first-rate high-energy physics laboratory which it has been in the past. (orig.)

  9. Foreword: Sir John Pendry FRS Sir John Pendry FRS

    Science.gov (United States)

    Inglesfield, John; Echenique, Pedro

    2008-07-01

    scattering is much weaker, and this allowed him to develop a method of successive approximation. The material and the calculation are cut up into a series of atomic slices, and the electronic structure solved without approximation in each slice. Being two-dimensional, this was much more manageable than a full three-dimensional calculation. Then the slices could be put together by a sort of perturbation theory to calculate the scattering current as a function of energy along each of the reciprocal lattice 'rods' allowed by the surface periodicity. John didn't just stop at having solved the problem in principle, he also developed a suite of computer codes to do the job in a routine way. He even published the code for all to use, and I believe that to the present day the calculations are still done effectively in the same way. Without the calculations, one cannot interpret the data in terms of a surface atomic structure. Effectively one is doing a computer experiment in parallel to the laboratory experiment, and one fiddles more or less systematically with the surface structure until one gets agreement between the simulations and the laboratory data. One of the things that John noticed was that the process of photoemission (UPS) from a surface is rather similar, and can be calculated in an analogous way. This suddenly became very important because the new synchrotron at Daresbury was about to become operational, pumping out billions of photons for solid state research. Sam Edwards (now Sir Sam) was head of SRC (forerunner of EPSRC) at the time and recognised the problem of interpreting all the data that the machine would provide. And after UPS would come EXAFS, and after that XANES and all the rest of the alphabet soup. With that foresight, unusual at the time, John Pendry was appointed to head the theory group at Daresbury. Previously the theoreticians had revolved around the nuclear physics accelerator, and John had to turn it completely around and refocus it, which he did

  10. John Adams and CERN: Personal Recollections

    CERN Document Server

    Brianti, Giorgio

    2013-01-01

    By any standards, John Adams had a most remarkable career. He was involved in three important, emerging technologies, radar, particle accelerators and controlled fusion, and had an outstanding impact on the last two. Without a university education, he attained hierarchical positions of the highest level in prestigious national and international organizations. This article covers the CERN part of his career, by offering some personal insights into the different facets of his contributions to major accelerator projects, from the first strong-focusing synchrotron, the PS, to the SPS and its conversion to a proton–antiproton collider. In particular, it outlines his abilities as a leader of an international collaboration, which has served as an example for international initiatives in other disciplines.

  11. Sir John and Lady Rita Cornforth: a distinguished chemical partnership.

    Science.gov (United States)

    Purchase, Rupert; Hanson, James R

    2015-01-01

    This review describes the life of Sir John Cornforth AC CBE FRS, who was awarded the Nobel Prize for Chemistry in 1975. It covers his early life in Australia, his work in Oxford, the National Institute for Medical Research, the Milstead Laboratory of Chemical Enzymology and the University of Sussex, together with the contributions made by his wife, Lady Rita Cornforth.

  12. SIR JOHN CRAWFORD MEMORIAL ADDRESS: Agriculture: The challenges of the 21st century

    OpenAIRE

    Beddington, Sir John

    2012-01-01

    The Sir John Crawford Memorial Address has been presented since 1985, in honour of the distinguished Australian civil servant, educator and agriculturalist in whose name the Crawford Fund was established. Sir John Crawford was a remarkable Australian who contributed at the highest levels, and was a passionate supporter of international agricultural research for development. This talk draws attention to four current and interrelated trends that suggest the world will be rather different by 202...

  13. The Failed Educations of John Stuart Mill and Henry Adams.

    Science.gov (United States)

    Crossley, Robert

    1979-01-01

    Analyzes and contrasts Mill's "Autobiography" and Adams'"The Education of Henry Adams" in order to present two approaches to the nature of education and of failure. Maintains that their perspectives may serve as catalysts and cautions for contemporary theories of education and its utility and relevance. (CAM)

  14. Spiro K. Antiochos Receives 2013 John Adam Fleming Medal: Citation

    Science.gov (United States)

    Klimchuk, James A.

    2014-01-01

    The John Adam Fleming Medal is awarded for "original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, space physics, and related sciences." Originality and technical leadership are exactly the characteristics that distinguish the research of Spiro K. Antiochos. Spiro possesses a truly unique combination of physical insight, creativity, and mastery of the concepts and mathematical and numerical tools of space physics. These talents have allowed him to develop completely original theories for major observational problems and to test and refine those theories using sophisticated numerical simulation codes that he himself helped to develop. Spiro's physical insight is especially impressive. He has an uncanny ability to identify the fundamental aspects of complex problems and to see physical connections where others do not. This can sometimes involve ideas that may initially seem counterintuitive to those with less creativity. Many of Spiro's revolutionary advances have opened up whole new areas of study and shaped the course of space physics. Examples include the breakout model for coronal mass ejections (CMEs), the S-web model for the slow solar wind, and the thermal nonequilibrium model for solar prominences. The breakout model is of special significance to AGU as it strives to promote science for the betterment of humanity. CMEs are enormous explosions on the Sun that can have major "space weather" impacts here on Earth. They affect technologies ranging from communication and navigation systems to electrical power grids. Breakout is the leading theory for why CMEs occur and may one day be the foundation for more accurate space weather forecasting.

  15. John Adams's Montesquieuean Moment: Enlightened Historicism in the Discourses on Davila.

    Science.gov (United States)

    Green, Jonathan

    2016-01-01

    At the outset of the French Revolution John Adams penned a series of Discourses of Davila, philosophical ruminations on the sixteenth-century French Wars of Religion. Recent historians have read these Discourses in terms of Adams's Machiavellianism-his conviction that men's passions lead to violence, if unrestrained. But this reading overlooks the extent to which Adams intended his Discourses as a particular investigation into the French nation's character, and into whether the revolutionaries could lay claim to a native, French tradition of mixed constitutional government. Situating the Discourses vis-à-vis Adams's contemporaneous reading of Montesquieu, this article argues for an underappreciated historicist dimension to his thought.

  16. Oceanographic data collected from the Sir John Franklin in the Beaufort Sea, September 1989

    Energy Technology Data Exchange (ETDEWEB)

    Macdonald, R W; Carmack, E C; O' Brien, M C; McLaughlin, F A; Minkley, B G; Berger-North, K

    1989-09-01

    The data reported here were collected from the Canadian Coast Guard ship Sir John Franklin during a cruise to the Canadian Beaufort Sea from August 21 to Sept 5, 1989. The cruise had two broad objectives: to collect chemical and conductivity temperature depth (CTD) data at a deep station in the Canadian Basin, and to survey intensively the shelf break with the Mackenzie Canyon as a focus. Conductivity temperature depth was measured using a CTD guideline system. Water samples consisting of hydrocast for 6 shelf edge stations at 200 m depth and one deep station at 3200 m depth were tested for salinity, temperature, dissolved oxygen, nutrients, and chlorophyll a. In addition, samples were collected for analysis of tritium, C-14, and oxygen isotope composition and acoustic profiles were run. Isotope composition and acoustic profile data are not included in this report.

  17. Sir John Macpherson, the first but sometimes overlooked Professor of Psychiatry at the University of Sydney.

    Science.gov (United States)

    White, Richard T

    2014-08-01

    To chronicle the creation of the Chair of Psychiatry at the University of Sydney, and the career and legacy, in New South Wales, of the first incumbent, Professor Sir John Macpherson CB MD FRCPE. The creation of the Chair, Macpherson's appointment, and his contributions to psychiatry in Sydney during the 52 months of his tenure, are well documented in contemporaneous sources and demonstrate that he was a very worthy Foundation Professor of Psychiatry at the University of Sydney. There are several possible reasons why Macpherson has been overlooked, including an erroneous statement in The World History of Psychiatry (1975) that William Siegfried Dawson, his successor from 1927 to 1952, was the first Professor of Psychiatry. © The Royal Australian and New Zealand College of Psychiatrists 2014.

  18. Overview of graduate training program of John Adams Institute for Accelerator Science

    Science.gov (United States)

    Seryi, Andrei

    The John Adams Institute for Accelerator Science is a center of excellence in the UK for advanced and novel accelerator technology, providing expertise, research, development and training in accelerator techniques, and promoting advanced accelerator applications in science and society. We work in JAI on design of novel light sources upgrades of 3-rd generation and novel FELs, on plasma acceleration and its application to industrial and medical fields, on novel energy recovery compact linacs and advanced beam diagnostics, and many other projects. The JAI is based on three universities - University of Oxford, Imperial College London and Royal Holloway University of London. Every year 6 to 10 accelerators science experts, trained via research on cutting edge projects, defend their PhD thesis in JAI partner universities. In this presentation we will overview the research and in particular the highly successful graduate training program in JAI.

  19. A turning point in the concept of justice: from Adam Smith to John Stuart Mill

    Directory of Open Access Journals (Sweden)

    Estrella Trincado Aznar

    2012-01-01

    Full Text Available Classical economists, John Stuart Mill included, based their theories on Adam Smith’s system. At some point, they labelled it as a "utilitarian" theory. However, Smith was non-utilitarian, perhaps even anti-utilitarian. One of the most amazing differences between classical economics versus Smithian theory consists of their concept of justice. Classical economics were based on a utilitarian concept; Smith criticizes the concept of utilitarian justice. Utility being a subjective picture, classical economists find it more difficult to draw limits to state intervention than Smith does. This paper compares Smith’s and John Stuart Mill’s concept of justice when they make the case for land tenure. Mill admits that society cannot properly be said to owe anything to the poor. However, not arguing from 'abstract rights,' but from 'utility' understood in its largest sense, Mill defended the nationalization of land. Mill was unable to draw any limits to state intervention. Conversely, Smith defended that justice is not a utilitarian concept. In this case, limits to state intervention are more easily drawn.

  20. A turning point in the concept of justice: from Adam Smith to John Stuart Mill

    Directory of Open Access Journals (Sweden)

    Estrella Trincado Aznar

    2015-07-01

    Full Text Available Classical economists, John Stuart Mill included, based their theories on Adam Smith’s system. At some point, they labelled it as a "utilitarian" theory. However, Smith was non-utilitarian, perhaps even anti-utilitarian. One of the most amazing differences between classical economics versus Smithian theory consists of their concept of justice. Classical economics were based on a utilitarian concept; Smith criticizes the concept of utilitarian justice. Utility being a subjective picture, classical economists find it more difficult to draw limits to state intervention than Smith does. This paper compares Smith’s and John Stuart Mill’s concept of justice when they make the case for land tenure. Mill admits that society cannot properly be said to owe anything to the poor. However, not arguing from 'abstract rights,' but from 'utility' understood in its largest sense, Mill defended the nationalization of land. Mill was unable to draw any limits to state intervention. Conversely, Smith defended that justice is not a utilitarian concept. In this case, limits to state intervention are more easily drawn.

  1. Florence Nightingale (1820-1910) and Sir John Forbes (1787-1861): neighbours in Old Burlington Street, Westminster.

    Science.gov (United States)

    Agnew, Robin

    2015-05-01

    The year 2010 marks the centenary of the birth of Florence Nightingale and will, no doubt, be universally remembered. Her life and nursing career have recently been fully described by Bostridge. It is less well known that her neighbour from November 1856 was the distinguished Scottish physician Sir John Forbes MD Edin FRCP Lond FRS DCL Oxon. Although they never met, they exchanged copies of each other's books and shared a mutual respect. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. Événement et trauma dans Doctor Atomic de John Adams

    Directory of Open Access Journals (Sweden)

    Mathieu Duplay

    2011-04-01

    , opéra de John Adams sur un livret de Peter Sellars, s’avère particulièrement instructif, non seulement parce qu’il y est question de l’un des plus violents traumatismes du xxe siècle — l’essai nucléaire de Los Alamos, prélude au bombardement atomique d’Hiroshima et de Nagasaki — mais encore parce que, non contente de mettre en scène l’impensable, cette œuvre met en évidence ce qui, de l’événement (qu’il soit historique ou esthétique, en appelle à une pensée encore informulée ; or c’est ce qui révèle sa nature traumatique, comme le discours de la psychanalyse le laisse entendre, parfois à son corps défendant.

  3. John Adams Lecture | Accelerator-Based Neutrino Physics: Past, Present and Future by Kenneth Long | 8 December

    CERN Multimedia

    2014-01-01

    John Adams Lecture: Accelerator-Based Neutrino Physics: Past, Present and Future by Dr. Kenneth Long (Imperial College London & STFC).   Monday, 8 December 2014 from 2 p.m. to 4 p.m. at CERN ( 503-1-001 - Council Chamber ) Abstract: The study of the neutrino is the study of physics beyond the Standard Model. We now know that the neutrinos have mass and that neutrino mixing occurs causing neutrino flavour to oscillate as neutrinos propagate through space and time. Further, some measurements can be interpreted as hints for new particles known as sterile neutrinos. The measured values of the mixing parameters make it possible that the matter-antimatter (CP) symmetry may be violated through the mixing process. The consequences of observing CP-invariance violation in neutrinos would be profound. To discover CP-invariance violation will require measurements of exquisite precision. Accelerator-based neutrino sources are central to the future programme and advances in technique are required ...

  4. Gerenciamento de Pessoas: Sobre a Formação dos Conceitos de Trabalho em Geral e em Abstrato: de John Locke a Adam Smith

    Directory of Open Access Journals (Sweden)

    Hermano Roberto Thiry-Cherques

    2009-01-01

    Full Text Available The evolution of management and technology of information associated with the moral and economic crises we attend in the last decade determined deep transformations in the way we manage and design organizations. The understanding of human factor role in production, mainly the use of concepts employed in human resources management, became inadequate to explain the phenomenon of work and to clarify its situation in the economic-organizational contemporary frame. In this article I seek to contribute to today’s reconstruction of people management conceptual corpus analyzing John Locke’s notion of work in general and Adam Smith’s notion of abstract work.

  5. El Mediterráneo a través de la ficción: el extraño caso de Sir John Mandeville

    Directory of Open Access Journals (Sweden)

    Morales Osorio, Susana

    2006-06-01

    Full Text Available

    The Travels of Sir John Mandeville presents the ficticious construction of the Orient through a travels tale which is primarily shaped as a pilgrimage to Jerusalem. Over and above the critical controversy about the existence of Sir John Mandeville, this book depicts in a very accurate way several key topics in the literature of the Middle Ages as it is the conception of the travel through the medieval peregrination, the homo viator as a consequence of the religious becoming which steamed the Middle Ages, or the Bible as the geography of the known world and the destination of the medieval curiosity. On the other hand, the tale shows a very special devising of the Other, of the unknown, by means of a mythical perspective, that is, through the recreation of fascinating mirabilia collection that still impress the current reader.



    Los viajes de Sir John Mandeville presenta la construcción ficticia del Oriente a través de un relato de viajes que se configura en primera instancia como una peregrinación a Jerusalén. La concepción del viaje a través de la peregrinatio medieval, el homo viator como consecuencia del devenir religioso que empaña la Edad Media, la Biblia como geografía del mundo conocido y como destino de la curiosidad medieval, tienen en la figura narrativa del Libro de las Maravillas del Caballero Sir John Mandeville una de sus mejores articulaciones, al margen de los problemas y

  6. O espectador imparcial de Adam Smith e o observador ideal de John Rawls: Uma crítica à ética utilitarista

    Directory of Open Access Journals (Sweden)

    Solange Regina Marin

    2015-03-01

    Full Text Available Resumo John Rawls fundamenta o utilitarismo na concepção de observador ideal presente nas teorias dos sentimentalistas escoceses do século XVIII, particularmente nas teorias de David Hume e Adam Smith. Como a tese do utilitarismo não é tão explícita e acessível na ótica de ambos os filósofos escoceses, pretendemos, no presente trabalho, confrontar a tese do espectador imparcial de Smith e a crítica de Rawls à concepção do observador ideal como fundadora do utilitarismo. Observamos maior abrangência para o espectador imparcial em relação ao observador ideal utilitarista nas escolhas morais.

  7. ADAMS - Introduction

    International Nuclear Information System (INIS)

    Song, Cheol Gi

    2003-06-01

    This book introduces ADAMS, which is composed of 20 modules ; stamping mechanism, ADAMS introduction, GUI overview failing stone project motion one DOF pendulum inclined plane lift mechanism I mechanism II mechanism III suspension subsystem suspension-steering system spring-damper I spring-damper II hatchback I hatchback II hatchback III cam-rocker-valve target practice recommended practice and switch mechanism workshop.

  8. the Cecil John Adams Travelling Fellowship

    African Journals Online (AJOL)

    1994-09-14

    Sep 14, 1994 ... 1886 it boasted a coffee-shop, two chemists and a branch of the Standard Bank. ... him a son in 1898 but the infant died at the age of 6 months. By 1900 Florence ... By this time, he had married Laura Green. She was carrying ...

  9. A Conversation with Adam Heller

    OpenAIRE

    Heller, A; Cairns, EJ

    2015-01-01

    © 2015 by Annual Reviews. All rights reserved. Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr....

  10. Sir John Struthers (1823-1899), Professor of Anatomy in the University of Aberdeen (1863-1889), President of the Royal College of Surgeons of Edinburgh (1895-1897).

    Science.gov (United States)

    Kaufman, M H

    2015-11-01

    Between 1841 and 1845 John Struthers attended both the University of Edinburgh and some of the various Extra-mural Schools of Medicine associated with Surgeons' Hall. While a medical student he became a Member of the Hunterian Medical Society of Edinburgh and later was elected one of their Annual Presidents. He graduated with the MD Edin and obtained both the LRCS Edin and the FRCS Edin diplomas in 1845. Shortly afterwards he was invited to teach Anatomy in Dr Handyside's Extra-mural School in Edinburgh. The College of Surgeons certified him to teach Anatomy in October 1847. He had two brothers, and all three read Medicine in Edinburgh. His younger brother, Alexander, died of cholera in the Crimea in 1855 while his older brother James, who had been a bachelor all his life, practised as a Consultant Physician in Leith Hospital, Edinburgh, until his death.When associated with Dr Handyside's Extra-mural School in Edinburgh, John taught Anatomy there until he was elected to the Chair of Anatomy in Aberdeen in 1863. Much of his time was spent in Aberdeen teaching Anatomy and in upgrading the administrative facilities there. He resigned from this Chair in 1889 and subsequently was elected President of Leith Hospital from 1891 to 1897. This was in succession to his older brother, James, who had died in 1891. Later, he was elected President of the Royal College of Surgeons of Edinburgh from 1895 to 1897 and acted as its Vice-President from 1897 until his death in 1899. In 1898, Queen Victoria knighted him. His youngest son, John William Struthers, was the only one of his clinically qualified sons to survive him and subsequently was elected President of the Edinburgh College of Surgeons from 1941 to 1943. © The Author(s) 2014.

  11. Ansel Adams: early works

    Science.gov (United States)

    Throckmorton, Jodi

    2010-02-01

    Ansel Adams (1902-1984), photographer, musician, naturalist, explorer, critic, and teacher, was a giant in the field of landscape photography. In his images of the unspoiled Western landscape, he strove to capture the sublime: the transcendentalist concept that nature can generate the experience of awe for the viewer. Many viewers are familiar with the heroic, high-contrast prints on high-gloss paper that Adams made to order beginning in the 1970s; much less well known are the intimate prints that the artist crafted earlier in his career. This exhibition focuses on these masterful small prints from the 1920s into the 1950s. During this time period, Adams's printing style changed dramatically. The painterly, soft-focus, warm-toned style of the Parmelian Prints of the High Sierras from the 1920s evolved into the sharp-focus style of the f/64 school of photography that Adams co-founded in the 1930s with Edward Weston and Imogen Cunningham. After World War II, Adams opted for a cooler, higher-contrast look for his prints. Throughout the various styles in which he chose to work, Adams explored the power of nature and succeeded in establishing landscape photography as a legitimate form of modern art.

  12. Whither Sir William?

    Directory of Open Access Journals (Sweden)

    Stephen J. Greenberg, MSLS, PhD

    2017-04-01

    Full Text Available There are times when something is simply so familiar that we can no longer see it at all. It can be a story, or a concept, or even a flesh-and-blood person. Familiarity breeds not only contempt, but a kind of invisibility as well. For too many of us, such is the case with Sir William Osler. In his time (1849–1919, many considered him to be one of the greatest practitioners, teachers, and writers ever in the field of medicine. He was instrumental in the founding of the Medical Library Association (MLA and was elected its second president.

  13. Lance-adams syndrome.

    Science.gov (United States)

    Shin, Jun-Hwa; Park, Jong Moon; Kim, A Ram; Shin, Hee Suk; Lee, Eun Shin; Oh, Min-Kyun; Yoon, Chul Ho

    2012-08-01

    It is not common for a patient who survives cardiac arrest to experience significant neurologic impairment such as acute and chronic post-hypoxic myoclonus, known as Lance-Adams syndrome. This syndrome is predominantly characterized by myoclonus that starts days to weeks after cardiopulmonary resuscitation in patients who regained consciousness. Although several cases of LAS were reported, the decisive treatment method has not been established. We report a 43 year old man with Lance-Adams syndrome who showed long-term improvement through treatment with anti-myoclonic agents and participation in a rehabilitation program.

  14. Sir Isaac Newton

    Directory of Open Access Journals (Sweden)

    E. A. Venter

    1964-03-01

    Full Text Available Die geweldige oplewing van die Christelike wetenskaps- gedagte in ons geeslose tyd, is ongetwyfeld ’n haas onverklaar- bare verskynsel. Dwarsdeur die eeue het Christene ook wetenskap beoefen saam met ongelowiges, maar dit was eers in ons leeftyd dat die principia van die Christelike religie ook vrugbaar gemaak is vir die wetenskapsbeoefening. In hierdie verband sal die name van Dooyeweerd, Vollenhoven, Stoker e.a. steeds met eer vermeld word. Natuurlik het belydende Christene ook voorheen wel deeglik saamgewerk aan die gebou van die wetenskap. Die intieme verband tussen religie, wysbegeerte en wetenskaps­ beoefening is toe egter nog nie suiwer ingesien nie. Uit hier­ die tydperk dateer die arbeid van sir Isaac Newton.

  15. The role of ADAMs in disease pathophysiology.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    The ADAMs are a family of multidomain transmembrane and secreted proteins involved in both proteolysis and cell adhesion. Altered expression of specific ADAMs is implicated in the pathophysiology of several diseases including rheumatoid arthritis, Alzheimer\\'s disease, cardiac hypertrophy, asthma and cancer. Of these different diseases, it is in cancer where most research has been carried out. Multiple ADAMs, including ADAM-9, ADAM-10, ADAM-12, ADAM-15 and ADAM-17, have been shown to play a role in either cancer formation or progression. Consistent with these findings, increased expression of specific ADAMs in several cancer types was found to correlate with features of aggressive disease and poor prognosis. Currently, selective ADAM inhibitors against ADAM-10 and ADAM-17 are undergoing clinical trials for the treatment of cancer. Further work is required in order to establish a causative role for ADAMs in rheumatoid arthritis, Alzheimer\\'s disease, cardiac hypertrophy and asthma.

  16. EVA 1 - ADAM 1

    International Nuclear Information System (INIS)

    Decken, C.B. von der; Fedders, H.; Hoehlein, B.

    1980-01-01

    The supplying of industry and households with heat is a central problem in our economy. The crisis background of oil supply renders a long-term secured heat supply with nuclear power plants a discussible alternative. The district heating in the form of hot water, which is heated in power plants and supplied to the consumer via district heating pipeline networks, however, is limited due to the unavoidable heat losses. To bridge long distances between the heat source and consumer and to maintain the heat at a high temperature level, there are distinct advantages in using the EVA-ADAM principle of long-distance energy transport. (orig.) [de

  17. John Adams Lecture | Lucio Rossi (CERN) | 3 December

    CERN Multimedia

    2012-01-01

    The Role of Superconducting Magnets for High Energy Physics, by Dr. Lucio Rossi, CERN Monday 3 December, 2012 at 2:30 p.m. Council Chamber, CERN Abstract: Superconducting Magnets have played a crucial role for the particle physics energy frontier. From Tevatron to the LHC, passing through HERA and RHIC, they have defined the last 30 years of hadron colliders. The talk will review the successful projects and mention the reasons and learning from the ill-fated projects, Isabelle and SSC. Technology spin-offs will be discussed, together with the development of the next generation magnets, the high-field ones, aimed at passing the 10 Tesla frontier in collider quality magnets, and the fast-cycled ones, aimed at enabling field ramp rates of 1 to 4 Tesla per second in synchrotron-quality magnets.

  18. Sir Karl Popper and Education

    Science.gov (United States)

    McNamara, D. R.

    1978-01-01

    Sir Karl Popper is one of England's most distinguished contemporary philosophers and it is surprising that his thought has not permeated and informed educational discussion. This paper suggests that educationists have much to learn from Karl Popper's writings and explores ways in which his ideas can illuminate and advance discussion about…

  19. Geim, Prof. Sir Andre Konstantin

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2015 Honorary. Geim, Prof. Sir Andre Konstantin FRS. Date of birth: 21 October 1958. Address: Royal Society Research Professor, University of Manchester, Oxford Road, Manchester M13 9PL, UK Contact: Office: (+44-161) 275 4120. Email: geim@manchester.ac.uk. YouTube; Twitter; Facebook ...

  20. A Conversation with Adam Heller.

    Science.gov (United States)

    Heller, Adam; Cairns, Elton J

    2015-01-01

    Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr. Heller, born in 1933, describes the enslavement of his father by Hungarians in 1942; the confiscation of his family's home, business, and all its belongings in 1944; and his incarceration in a brick factory with 18,000 Jews who were shipped by the Hungarians to be gassed by Germans in Auschwitz. Dr. Heller and his immediate family survived the Holocaust and arrived in Israel in 1945. He studied under Ernst David Bergmann at the Hebrew University, and then worked at Bell Laboratories and GTE Laboratories, where he headed Bell Lab's Electronic Materials Research Department. At GTE Laboratories, he built in 1966 the first neodymium liquid lasers and in 1973 with Jim Auborn conceived and engineered the lithium thionyl chloride battery, one of the first to be manufactured lithium batteries, which is still in use. After joining the faculty of engineering of The University of Texas at Austin, he cofounded with his son Ephraim Heller TheraSense, now a major part of Abbott Diabetes Care, which produced a microcoulometer that made the monitoring of glucose painless by accurately measuring the blood glucose concentration in 300 nL of blood. He also describes the electrical wiring of enzymes, the basis for Abbott's state-of-the-art continuous glucose monitoring system. He discusses his perspective of reducing the risk of catastrophic global warming in a wealth-accumulating, more-energy-consuming world and provides advice for students entering careers in science or engineering.

  1. John Stachel

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. John Stachel. Articles written in Resonance – Journal of Science Education. Volume 3 Issue 8 August 1998 pp 76-92 Reflections. Albert Einstein-The Man Behind the Myths · John Stachel · More Details Fulltext PDF ...

  2. The Johns Hopkins Hospital: A Summer Internship

    OpenAIRE

    Smith, Adam

    2016-01-01

    Adam Smith, a native of Richmond, Indiana, is an advanced pharmacy practice student in the College of Pharmacy at Purdue University. In this article, he describes how career exploration through a summer internship with The Johns Hopkins Hospital in Baltimore, Maryland solidified his desire to pursue a career in pharmacy administration.

  3. Adam Smith and dependency.

    Science.gov (United States)

    Ozler, Sule

    2012-06-01

    The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

  4. Adam Smith on population.

    Science.gov (United States)

    Spengler, J J

    1970-11-01

    Abstract Adam Smith dealt with questions of population mainly in his Wealth of Nations. His discussion falls roughly under five heads and reflects in considerable measure his image of the English economy. (1) A country's population capacity, given the average level of consumption, was conditioned by the stock of land, the skill with which it was cultivated, and the degree to which division of labour could be increased and thereby augment output for domestic use and sale in external markets. (2) Growth of population was essentially in response to growth of the demand for labour and served to increase division of labour. (3) The social mechanisms underlying elevation of the scale of living are touched upon, and in an optimistic spirit. (4) The distribution of a country's population responded to its progress in opulence, with the rate of this progress conditioned by the degree to which inappropriate (e.g. mercantilist) policies were avoided. (5) Smith dealt briefly with such matters as colonies, education, size of economy, environmental influences, and public policy, all of which he recognized as significant for the quantity and quality of a country's numbers.

  5. King, Prof. Sir David Anthony

    Indian Academy of Sciences (India)

    Elected: 1998 Honorary. King, Prof. Sir David Anthony Sc.D., FRS. Date of birth: 12 August 1939. Address: Chief Scientific Adivser & Head, Office of Science and Innovation, London SW1H 0ET, U.K.. Contact: Office: (+44-020) 7215 3821. Fax: (+44-020) 7215 0314. Email: mpst.king@dti.gsi.gov.uk, dak10@cus.cam.ac.uk.

  6. DARPA ADAMS Project

    Science.gov (United States)

    2015-05-11

    it means that Mary distrusts John. We showed that it is possible to analyze such trust- distrust relationships within signed social networks in... relationship problems) − Professional Problems (negative changes at workplace, interpersonal conflicts) Furthermore, we encode in 2nd degree variables...a social media forum data. • Processed initial set of Vegas metrics data (clustering coefficient, # similar users, # skip levels) through time

  7. 50 Years of synchrotrons Adams' Memorial lecture

    CERN Document Server

    Lawson, J D; CERN. Geneva

    1996-01-01

    Fifty years ago Frank Goward of the Atomic Energy Research Establishment Group at Malvern converted a small American betatron to make the worldÕs first synchrotron. At the same time Marcus Oliphant was planning to build at Birmingham a large proton machine with a ring magnet and variable magnetic field. Ideas for this had come to him during night-shifts tending the electromagnetic separators at Oak Ridge during the war. Some seven years later, in 1953, a group gathered together in Geneva to build the PS. A major contributor to the design work which had made this possible was John Adams. An account of some of the achievements in these eventful years will be presented. CERN has built nine synchrotrons/colliders and two temporary test rings. Eight machines are still running. The review will start with the PS, the first proton synchrotron based on the alternating gradient principle invented in 1952 at BNL. The design work of the PS team, under the enlightened leadership of J.B. Adams, and the construction of the...

  8. ADAMS executive and operating system

    Science.gov (United States)

    Pittman, W. D.

    1981-01-01

    The ADAMS Executive and Operating System, a multitasking environment under which a variety of data reduction, display and utility programs are executed, a system which provides a high level of isolation between programs allowing them to be developed and modified independently, is described. The Airborne Data Analysis/Monitor System (ADAMS) was developed to provide a real time data monitoring and analysis capability onboard Boeing commercial airplanes during flight testing. It inputs sensor data from an airplane performance data by applying transforms to the collected sensor data, and presents this data to test personnel via various display media. Current utilization and future development are addressed.

  9. What's an Adam's Apple? (For Kids)

    Science.gov (United States)

    ... for Educators Search English Español What's an Adam's Apple? KidsHealth / For Kids / What's an Adam's Apple? Print You're at the high school baseball ... the throat. This is what's called an Adam's apple. Everyone's larynx grows during puberty, but a girl's ...

  10. John Lindsay

    CERN Multimedia

    2005-01-01

    A few weeks ago John Lindsay passed away unexpectedly at his home in St. Genis. With his death we have lost a pioneer in detector electronics and one of the founding fathers of the CERN Electronics Group. John came to CERN in 1956 to join the Electronics Group, which was being formed in the SC Division. He thus participated from the beginning in the design, development, production, commissioning and support of electronics for the experiments at the CERN accelerators, initially at the SC and finally at the SPS. From the University of Glasgow he brought his expertise on pulse height analyzers, which were called kick sorters in those days, and did pioneering work with it in the early CERN experiments. He designed read-out systems for successive generations of detectors, such as wire spark chambers, multiwire proportional chambers, calorimeters, etc., often coming up with innovative solutions. Surely one of his finest moments must have been when he worked on complex detector systems, such as liquid argon calo...

  11. "Issi, sa piat ise usguma et sa osgad!" / John Whitmore ; intervjueerinud Endrik Randoja

    Index Scriptorium Estoniae

    Whitmore, John

    2010-01-01

    Juhtiva coaching'u-eksperdi ja Tartus toimuva personalijuhtimise konverentsi "Uuenev organisatsioon" peaesineja sir John Whitmore'i hinnangul on coaching viis mõista ja toetada inimesi ning tõsta nende eneseusku

  12. Smith, Adam (1723-90)

    DEFF Research Database (Denmark)

    Bouchet, Dominique

    2015-01-01

    Adam Smith is often said to have been the founder of the science of economics and the father of liberalism in the sphere of economics. In fact he was neither. He lived at a turning point in western economic and political history, one that was littered with disruptive developments. He came up...... with a masterful synthesis of the economic knowledge of his period and emphasized both the relative autonomy of these phenomena and their importance in terms of generating wealth from, and in the interests of, everyone. Nevertheless, Smith never denied the moral foundation of economic behavior....

  13. Activation of ADAM 12 protease by copper

    DEFF Research Database (Denmark)

    Loechel, F; Wewer, Ulla M.

    2001-01-01

    Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimina......Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency......: elimination of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism...... for ADAM 12 involving both furin cleavage and copper binding....

  14. Peter St. John | NREL

    Science.gov (United States)

    St. John Photo of Peter St. John Peter St. John Researcher III-Chemical Engineering Peter.StJohn @nrel.gov | 303-384-7969 Orcid ID http://orcid.org/0000-0002-7928-3722 Education Peter St. John received his engineering from the University of California at Santa Barbara in 2015. During his Ph.D., St. John applied

  15. Tectonic geomorphology of the Andes with SIR-A and SIR-B

    Science.gov (United States)

    Bloom, Arthur L.; Fielding, Eric J.

    1986-01-01

    Data takes from SIR-A and SIR-B (Shuttle Imaging Radar) crossed all of the principal geomorphic provinces of the central Andes between 17 and 34 S latitude. In conjunction with Thematic Mapping images and photographs from hand-held cameras as well as from the Large Format Camera that was flown with SIR-B, the radar images give an excellent sampling of Andean geomorphology. In particular, the radar images show new details of volcanic rocks and landforms of late Cenozoic age in the Puna, and the exhumed surfaces of tilted blocks of Precambrian crystalline basement in the Sierras Pampeanas.

  16. Sir Charles Scott Sherrington (1857–1952)

    Indian Academy of Sciences (India)

    Twentieth century bore witness to remarkable scientists whohave advanced our understanding of the brain. Among them,Sir Charles Scott Sherrington's ideas about the way in whichthe central nervous system operates has continuing relevanceeven today. He received honorary doctorates from twentytwouniversities and ...

  17. Sir Ronald Ross and the Malarial Parasite

    Indian Academy of Sciences (India)

    1997-08-20

    Aug 20, 1997 ... In 1857, a General in the Indian Army, Sir C C G Ross and his wife Matilda .... generally low-caste Indians who required a fee before drinking the water and ... nary demand being made upon their systems, as by fatigue, chill,.

  18. Sir Ronald Ross and the Malarial Parasite

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 11; Issue 7. Sir Ronald Ross and the Malarial Parasite - Discovery of its Route - From Man to Mosquito and Back. Shobhona Sharma. General Article Volume 11 Issue 7 July 2006 pp 4-13 ...

  19. Sir Charles Scott Sherrington (1857–1952)

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Twentieth century bore witness to remarkable scientists whohave advanced our understanding of the brain. Among them,Sir Charles Scott Sherrington's ideas about the way in whichthe central nervous system operates has continuing relevanceeven today. He received honorary doctorates from ...

  20. Adam Smith’s contribution to secularisation

    Directory of Open Access Journals (Sweden)

    Petrus Simons

    2013-06-01

    Full Text Available This article examined several crucial themes in Adam Smith’s philosophy with the purpose of highlighting and assessing his contribution to the secularisation of Western society. The article, written from the perspective of reformational philosophy, begins with a brief biography and sketch of Adam Smith’s influence on modern society, followed by a summary of Ponti Venter’s view on Smith. This sets the scene for a discussion of Adam Smith’s project, his method of tackling it, and his views on systems, philosophy of history and the concept of philosophy.

  1. ADAM: Analyzer for Dialectal Arabic Morphology

    Directory of Open Access Journals (Sweden)

    Wael Salloum

    2014-12-01

    Full Text Available While Modern Standard Arabic (MSA has many resources, Arabic Dialects, the primarily spoken local varieties of Arabic, are quite impoverished in this regard. In this article, we present ADAM (Analyzer for Dialectal Arabic Morphology. ADAM is a poor man’s solution to quickly develop morphological analyzers for dialectal Arabic. ADAM has roughly half the out-of-vocabulary rate of a state-of-the-art MSA analyzer and is comparable in its recall performance to an Egyptian dialectal morphological analyzer that took years and expensive resources to build.

  2. ADAM9 Is a Novel Product of Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Roychaudhuri, Robin; Hergrueter, Anja H; Polverino, Francesca

    2014-01-01

    A disintegrin and a metalloproteinase domain (ADAM) 9 is known to be expressed by monocytes and macrophages. In this study, we report that ADAM9 is also a product of human and murine polymorphonuclear neutrophils (PMNs). ADAM9 is not synthesized de novo by circulating PMNs. Rather, ADAM9 protein...

  3. ADAM 12 protease induces adipogenesis in transgenic mice

    DEFF Research Database (Denmark)

    Kawaguchi, Nobuko; Xu, Xiufeng; Tajima, Rie

    2002-01-01

    ADAM 12 (meltrin-alpha) is a member of the ADAM (a disintegrin and metalloprotease) family. ADAM 12 functions as an active metalloprotease, supports cell adhesion, and has been implicated in myoblast differentiation and fusion. Human ADAM 12 exists in two forms: the prototype membrane-anchored pr......ADAM 12 (meltrin-alpha) is a member of the ADAM (a disintegrin and metalloprotease) family. ADAM 12 functions as an active metalloprotease, supports cell adhesion, and has been implicated in myoblast differentiation and fusion. Human ADAM 12 exists in two forms: the prototype membrane......-anchored protein, ADAM 12-L, and a shorter secreted form, ADAM 12-S. Here we report the occurrence of adipocytes in the skeletal muscle of transgenic mice in which overexpression of either form is driven by the muscle creatine kinase promoter. Cells expressing a marker of early adipogenesis were apparent...

  4. Adam Smith y el derecho

    Directory of Open Access Journals (Sweden)

    Federico Escobar Córdoba

    2004-12-01

    Full Text Available Este artículo destaca el análisis jurídico en la obra de Adam Smith y su enriquecedor método de estudiar el derecho, particularmente en sus Lecciones de jurisprudencia. Esboza el contexto jurídico de las Lecciones e informa sobre su público original. Luego, describe la presencia del derecho romano en esa obra, deteniéndose en dos aspectos que los editores de la Edición Glasgow señalaron como errores o imprecisiones. El artículo analiza estos aspectos, ofrece posibles explicaciones alternativas que, a la vez, resaltan la complejidad del pensamiento jurídico de Smith. Finalmente, identifica tres niveles de análisis, empleados por Smith en las Lecciones, cuya interacción sería una contribución importante a la dogmática jurídica contemporánea.

  5. Sumoylation of Sir2 differentially regulates transcriptional silencing in yeast.

    Science.gov (United States)

    Hannan, Abdul; Abraham, Neethu Maria; Goyal, Siddharth; Jamir, Imlitoshi; Priyakumar, U Deva; Mishra, Krishnaveni

    2015-12-02

    Silent information regulator 2 (Sir2), the founding member of the conserved sirtuin family of NAD(+)-dependent histone deacetylase, regulates several physiological processes including genome stability, gene silencing, metabolism and life span in yeast. Within the nucleus, Sir2 is associated with telomere clusters in the nuclear periphery and rDNA in the nucleolus and regulates gene silencing at these genomic sites. How distribution of Sir2 between telomere and rDNA is regulated is not known. Here we show that Sir2 is sumoylated and this modification modulates the intra-nuclear distribution of Sir2. We identify Siz2 as the key SUMO ligase and show that multiple lysines in Sir2 are subject to this sumoylation activity. Mutating K215 alone counteracts the inhibitory effect of Siz2 on telomeric silencing. SUMO modification of Sir2 impairs interaction with Sir4 but not Net1 and, furthermore, SUMO modified Sir2 shows predominant nucleolar localization. Our findings demonstrate that sumoylation of Sir2 modulates distribution between telomeres and rDNA and this is likely to have implications for Sir2 function in other loci as well. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. SIR - small is safe [in reactor design

    International Nuclear Information System (INIS)

    Hayns, M.

    1989-01-01

    A joint USA-UK venture has been initiated to design a small nuclear reactor which offers low capital cost, greater flexibility and a potentially lower environmental impact. Called Safe Integral Reactor (SIR), the lead unit could be built in the United Kingdom Atomic Energy Authority's (UKAEA's) Winfrith site if the design is accepted by the UK Nuclear Installations Inspectorate (NII). This article describes the 320 MWe reactor unit that is the basis of the design being developed. (author)

  7. The mitochondrial SIR2 related protein 2 (SIR2RP2 impacts Leishmania donovani growth and infectivity.

    Directory of Open Access Journals (Sweden)

    Nimisha Mittal

    2017-05-01

    Full Text Available Leishmania donovani, a protozoan parasite is the major causative agent of visceral leishmaniasis. Increased toxicity and resistance to the existing repertoire of drugs has been reported. Hence, an urgent need exists for identifying newer drugs and drug targets. Previous reports have shown sirtuins (Silent Information Regulator from kinetoplastids as promising drug targets. Leishmania species code for three SIR2 (Silent Information Regulator related proteins. Here, we for the first time report the functional characterization of SIR2 related protein 2 (SIR2RP2 of L. donovani.Recombinant L. donovani SIR2RP2 was expressed in E. coli and purified. The enzymatic functions of SIR2RP2 were determined. The subcellular localization of LdSIR2RP2 was done by constructing C-terminal GFP-tagged full-length LdSIR2RP2. Deletion mutants of LdSIR2RP2 were generated in Leishmania by double targeted gene replacement methodology. These null mutants were tested for their proliferation, virulence, cell cycle defects, mitochondrial functioning and sensitivity to known SIR2 inhibitors.Our data suggests that LdSIR2RP2 possesses NAD+-dependent ADP-ribosyltransferase activity. However, NAD+-dependent deacetylase and desuccinylase activities were not detected. The protein localises to the mitochondrion of the promastigotes. Gene deletion studies showed that ΔLdSIR2RP2 null mutants had restrictive growth phenotype associated with accumulation of cells in the G2/M phase and compromised mitochondrial functioning. The null mutants had attenuated infectivity. Deletion of LdSIR2RP2 resulted in increased sensitivity of the parasites to the known SIR2 inhibitors. The sirtuin inhibitors inhibited the ADP-ribosyltransferase activity of recombinant LdSIR2RP2. In conclusion, sirtuins could be used as potential new drug targets for visceral leishmaniasis.

  8. Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice

    Directory of Open Access Journals (Sweden)

    Postina Rolf

    2009-02-01

    Full Text Available Abstract Background In a transgenic mouse model of Alzheimer disease (AD, cleavage of the amyloid precursor protein (APP by the α-secretase ADAM10 prevented amyloid plaque formation, and alleviated cognitive deficits. Furthermore, ADAM10 overexpression increased the cortical synaptogenesis. These results suggest that upregulation of ADAM10 in the brain has beneficial effects on AD pathology. Results To assess the influence of ADAM10 on the gene expression profile in the brain, we performed a microarray analysis using RNA isolated from brains of five months old mice overexpressing either the α-secretase ADAM10, or a dominant-negative mutant (dn of this enzyme. As compared to non-transgenic wild-type mice, in ADAM10 transgenic mice 355 genes, and in dnADAM10 mice 143 genes were found to be differentially expressed. A higher number of genes was differentially regulated in double-transgenic mouse strains additionally expressing the human APP[V717I] mutant. Overexpression of proteolytically active ADAM10 affected several physiological pathways, such as cell communication, nervous system development, neuron projection as well as synaptic transmission. Although ADAM10 has been implicated in Notch and β-catenin signaling, no significant changes in the respective target genes were observed in adult ADAM10 transgenic mice. Real-time RT-PCR confirmed a downregulation of genes coding for the inflammation-associated proteins S100a8 and S100a9 induced by moderate ADAM10 overexpression. Overexpression of the dominant-negative form dnADAM10 led to a significant increase in the expression of the fatty acid-binding protein Fabp7, which also has been found in higher amounts in brains of Down syndrome patients. Conclusion In general, there was only a moderate alteration of gene expression in ADAM10 overexpressing mice. Genes coding for pro-inflammatory or pro-apoptotic proteins were not over-represented among differentially regulated genes. Even a decrease of

  9. Bordism, stable homotopy and adams spectral sequences

    CERN Document Server

    Kochman, Stanley O

    1996-01-01

    This book is a compilation of lecture notes that were prepared for the graduate course "Adams Spectral Sequences and Stable Homotopy Theory" given at The Fields Institute during the fall of 1995. The aim of this volume is to prepare students with a knowledge of elementary algebraic topology to study recent developments in stable homotopy theory, such as the nilpotence and periodicity theorems. Suitable as a text for an intermediate course in algebraic topology, this book provides a direct exposition of the basic concepts of bordism, characteristic classes, Adams spectral sequences, Brown-Peter

  10. St. John's Wort (image)

    Science.gov (United States)

    The herb St. John's Wort is believed to be helpful in relieving mild to moderate depression, but should only be taken under a physician's supervision. St. John's Wort may clash with other medications or ...

  11. "Cet obscur objet du Désir"

    Directory of Open Access Journals (Sweden)

    Reto Melchior

    1996-09-01

    Full Text Available Luis Bunuel’s last film is based on Pierre Louÿs’ La Femme et le Pantin. This now forgotten bestseller, published in 1898, is drawn from Goya s painting El Pelele, in which four women are playing with a male puppet. In Pierre Louÿs’ novel this scene is inverted so that one woman with two faces plays with four men. In Cet Obscur Objet du Désir this “femme fatale” is interpreted by two actresses. The concentric structure of the film puts focus on a scene of being excluded from knowing. The technique of continually interrupting the flash-back sequences frustrates the audience because of its exclusion from the “real” course of events and gives rise to doubts whether the male protagonist tells the truth about his love-affair or whether he satisfies the curiosity of the audience by telling them Pierre Louÿs’ novel as his own story. This ambiguous art of narration mirrors Bunuel’s claim that the main topic of Cet Obscur Objet du Désir is frustration.

  12. Adam Smith and the Rhetoric of Style.

    Science.gov (United States)

    Moran, Michael G.

    Historians of rhetoric have generally accepted the view that Adam Smith rejected the principles of classical rhetoric. However, while there can be no doubt that Smith greatly truncated the five classical arts of rhetoric (invention, arrangement, style, memory, and delivery) by reducing his concerns largely to style and arrangement, he did not…

  13. Adam Smith, Religion, and Tuition Tax Credits.

    Science.gov (United States)

    Alexander, Kern

    1983-01-01

    Examines tuition tax credit programs in framework of Adam Smith's ideas on the economic impact of established churches. Finds that tuition tax credits would amount to state expenditures to relieve the financial burden of parochial school parents and would allow churches to invest commercially to maintain their charitable functions. (JW)

  14. Adam Smith's bougeois virtues in competition

    NARCIS (Netherlands)

    Wells, T.; Graafland, J.J.

    2012-01-01

    Whether or not capitalism is compatible with ethics is a long standing dispute. We take up an approach to virtue ethics inspired by Adam Smith and consider how market competition influences the virtues most associated with modern commercial society. Up to a point, competition nurtures and supports

  15. J. B. Adams Acting Director-General

    CERN Multimedia

    1960-01-01

    After the tragic death of Prof. C. J. Bakker, the Council of CERN held an emergency meeting on May 3, 1960. Following this session, Mr. F. de Rose, President of the Council of the European Organization for Nuclear Research, announced the appointment of Mr. J. B. Adams, Director of the PS division to the post of acting Director-General.

  16. Adam Smith : Systematic Philosopher and Public Thinker

    NARCIS (Netherlands)

    Schliesser, E.

    2017-01-01

    This book treats Adam Smith as a systematic philosopher. Smith was a giant of the Scottish Enlightenment with polymath interests. The book explores Smith’s economics and ethics in light of his other commitments on the nature of knowledge, the theory of emotions, the theory of mind, his account of

  17. Human ADAM 12 (meltrin alpha) is an active metalloprotease

    DEFF Research Database (Denmark)

    Loechel, F; Gilpin, B J; Engvall, E

    1998-01-01

    The ADAMs (a disintegrin and metalloprotease) are a family of multidomain proteins with structural homology to snake venom metalloproteases. We recently described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this report we provide evidence that the metalloprotease domain of ADAM...

  18. Role of ADAMs in cancer formation and progression.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    The ADAMs (a disintegrin and metalloproteinase) comprise a family of multidomain transmembrane and secreted proteins. One of their best-established roles is the release of biologically important ligands, such as tumor necrosis factor-alpha, epidermal growth factor, transforming growth factor-alpha, and amphiregulin. Because these ligands have been implicated in the formation and progression of tumors, it might be expected that the specific ADAMs involved in their release would also be involved in malignancy. Consistent with this hypothesis, emerging data from model systems suggest that ADAMs, such as ADAM-9, ADAM-12, ADAM-15, and ADAM-17, are causally involved in tumor formation\\/progression. In human cancer, specific ADAMs are up-regulated, with levels generally correlating with parameters of tumor progression and poor outcome. In preclinical models, selective ADAM inhibitors against ADAM-10 and ADAM-17 have been shown to synergize with existing therapies in decreasing tumor growth. The ADAMs are thus a new family of potential targets for the treatment of cancer, especially malignancies that are dependent on human epidermal growth factor receptor ligands or tumor necrosis factor-alpha.

  19. Connective tissue growth factor is a substrate of ADAM28

    International Nuclear Information System (INIS)

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko; Fujii, Yutaka; Jinno, Hiromitsu; Okada, Yasunori

    2010-01-01

    Research highlights: → The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. → ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF 165 complex. → CTGF digestion by ADAM28 releases biologically active VEGF 165 from the complex. → ADAM28, CTGF and VEGF 165 are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. → These suggest that ADAM28 promotes VEGF 165 -induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF 165 complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala 181 -Tyr 182 and Asp 191 -Pro 192 bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor 165 (VEGF 165 ), releasing biologically active VEGF 165 from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF 165 -induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF 165 complex.

  20. [Sir Francis Galton: the father of eugenics].

    Science.gov (United States)

    Aubert-Marson, Dominique

    2009-01-01

    Not only was Sir Francis Galton a famous geographer and statistician, he also invented "eugenics" in 1883. Eugenics, defined as the science of improving racial stock, was developed from a new heredity theory, conceived by Galton himself, and from the evolution theory of Charles Darwin, transposed to human society by Herbert Spencer. Galton's eugenics was a program to artificially produce a better human race through regulating marriage and thus procreation. Galton put particular emphasis on "positive eugenics", aimed at encouraging the physically and mentally superior members of the population to choose partners with similar traits. In 1904, he presented his ideas in front of a vast audience of physicians and scientists in London. His widely-publicized lecture served as the starting point for the development of eugenics groups in Europe and the United States during the first half of the 20th century.

  1. ADAM (Affordable Desktop Application Manager): a Unix desktop application manager

    International Nuclear Information System (INIS)

    Liebana, M.; Marquina, M.; Ramos, R.

    1996-01-01

    ADAM stands for Affordable Desktop Application Manager. It is a GUI developed at CERN with the aim to ease access to applications. The motivation to develop ADAM came from the unavailability of environments like COSE/CDE and their heavy resource consumption. ADAM has proven to be user friendly: new users are able to customize it to their needs in few minutes. Groups of users may share through ADAM a common application environment. ADAM also integrates the Unix and the PC world. PC users can excess Unix applications in the same way as their usual Windows applications. This paper describes all the ADAM features, how they are used at CERN Public Services, and the future plans for ADAM. (author)

  2. Book in three volumes of dr. John Puricha: Theology and pedagogy of St. John Chrysostom

    Directory of Open Access Journals (Sweden)

    Parlić-Božović Jasna Lj.

    2011-01-01

    Full Text Available Before the is latest work of Bishop Dr John Puric, by its importance, analytically decorated works, an impressive and voluminous number of facts happy including pedagogical Serbian public. Specifically, our pedagogical public is missing in this way displayed the Orthodox point of view of observation pedagogical crown and top categories. Episkom John was the there / volume work attempted to provide the interested reader the personality profile of any precise data from the conception of St. John Crisostom by looking at the same time as its pedagogy, and theology. Moreover these two concepts and bringing them to their assence, John episcope them actually connects into one inseparable unity. Therefore, this work has a multiple value and importance esportance especially for educators, who have not tried or had the oppotunality to see and understand the pedagogy of Orthodox theology in general, decorated with the ideas of Saint John Chrysostom special. Mindfullpeace as heir and successor creative Cappadocia 'novonikejske' trijadologije, St. John Chrystom recognizes the statut of Divine pedagogy educational philanthropy and philanthropic saving of pedagogy in each of the three Divine Persons. God the Father is this part, written by Bishop John, and from the perspective of John Chrysostom, is uncreated and unborn educationak philanthropy source of grace of the Holy Trinity. God the Son, and of the Father, uncreated etrinilly born, only begotten Son of God, newborn Logos, Jesus Christ the God/ man, BewAdam is alive and saving, hypostatic Ikonomija God, great mystery of the faith- God is reported in the body, the Divine Krishna- resurrect pedagogy, in which the comic-eschatologiocal Body, Church of Heaven and Earth, The Secret New Substances contain - the salvation of all creation, all creatures animate and inanimate. The salvation of man and the world, in the Divine dispensation and the pedagogy of salvation invation involve all there persons of the Holy

  3. Dos obras del escultor neoclásico inglés John Francis (1780- 1861 en una colección particular española

    Directory of Open Access Journals (Sweden)

    Quintanilla Martínez, Emilio

    2012-09-01

    Full Text Available Two previously unknown works by the British neoclassical sculptor John Francis dating from the second quarter of the 19th century, representing the 1st Duke of Sutherland and, most likely, the sculptor Sir John Francis, have been located in a Spanish private collection.

    Dos obras, hasta ahora inéditas, del escultor neoclásico inglés John Francis del segundo cuarto del siglo XIX, y que representan al primer duque de Sutherland y seguramente al escultor Sir John Francis, en colección privada española.

  4. MBS Analysis Of Kinetic Structures Using ADAMS

    DEFF Research Database (Denmark)

    Kirkegaard, Poul Henning; Nielsen, Søren R.K.

    2009-01-01

    The present paper considers multibody system (MBS) analysis of kinetic structures using the software package ADAMS. Deployable, foldable, expandable and reconfigurable kinetic structures can provide a change in the geometric morphology of the envelope by contributing to making it adaptable to e.......g. changing external climate factors, in order to improve the indoor climate performance of the building. The derivation of equations of motion for such spatial mechanical systems is a challenging issue in scientific community. However, with new symbolic tools one can automatically derive equations in so......-called multibody system (MBS) formalism. The present paper considers MBS modeling of kinetic architectural structures using the software packages ADAMS. As a result, it is found that symbolic MBS simulation tools facilitate a useful evaluation environment for MBS users during a design phase of responsive kinetic...

  5. IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

    Science.gov (United States)

    Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

    2017-10-01

    on periostin-rich extracellular matrix in the asthmatic airway in an ADAM8-dependent manner, making ADAM8 a possible therapeutic target. © 2017 John Wiley & Sons Ltd.

  6. An archaeology of Adam Smith's epistemic context

    OpenAIRE

    Vigo de Lima, I.; Guizzo, D.

    2015-01-01

    Adam Smith played a key role in Foucault's archaeology of political economy. This archaeology, which Foucault accomplished in The Order of Things, is the focus of this article. Foucault may have disagreed with the writings of the classical political economists but he widens our perspective through new possibilities of understanding. It is very illuminating to understand Smith's thinking as following a discursive practice that economic thought shared with the knowledge of living beings (natura...

  7. John Dewey, an Appreciation

    Science.gov (United States)

    Clopton, Robert W.

    2015-01-01

    The subject of the annual Presidential address of Phi Kappa Phi, presented on May 8, 1962, was John Dewey. Dewey is identified in the public mind chiefly as an educational philosopher. In this address, the author describes the life and work of John Dewey as an indefatigable student of life whose interests ranged, like those of Aristotle, over the…

  8. John P Craig

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. John P Craig. Articles written in Resonance – Journal of Science Education. Volume 17 Issue 10 October 2012 pp 924-925 Article-in-a-Box. S N De - An Appreciation · John P Craig · More Details Fulltext PDF ...

  9. A John Wilson

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. A John Wilson. Articles written in Resonance – Journal of Science Education. Volume 11 Issue 7 July 2006 pp 70-76 Classroom. Inverting Matrices Constructed from Roots of Unity · A John Wilson · More Details Fulltext PDF ...

  10. Adam Smith, Market and Social Change

    DEFF Research Database (Denmark)

    Bouchet, Dominique

    2017-01-01

    Adam Smith (1723-1790) provided us with a remarkable synthesis of the economic and political ideas of his time and developed a conceptual system to analyse social interactions that mattered for the wealth of nations. He proposed a radically different roadmap for the future development of the soci......Adam Smith (1723-1790) provided us with a remarkable synthesis of the economic and political ideas of his time and developed a conceptual system to analyse social interactions that mattered for the wealth of nations. He proposed a radically different roadmap for the future development...... of the society he lived in. The fact that his original analyses were rooted in a given historical context and were founded on a well thought-through conceptual system should not be ignored. The galvanising effect of the dribs and drabs of Adam Smith ideas that have been bandied about are a long way from...... the powerful insights imbued in the original ideas. Putting those back into context, looking into how Smith proceeded then, trying to update his observations, might help us to be more attentive to the market changes and social challenges of our times....

  11. Sir Victor Horsley: pioneer craniopharyngioma surgeon.

    Science.gov (United States)

    Pascual, José M; Prieto, Ruth; Mazzarello, Paolo

    2015-07-01

    Sir Victor Horsley (1857-1916) is considered to be the pioneer of pituitary surgery. He is known to have performed the first surgical operation on the pituitary gland in 1889, and in 1906 he stated that he had operated on 10 patients with pituitary tumors. He did not publish the details of these procedures nor did he provide evidence of the pathology of the pituitary lesions operated on. Four of the patients underwent surgery at the National Hospital for Neurology and Neurosurgery (Queen Square, London), and the records of those cases were recently retrieved and analyzed by members of the hospital staff. The remaining cases corresponded to private operations whose records were presumably kept in Horsley's personal notebooks, most of which have been lost. In this paper, the authors have investigated the only scientific monograph providing a complete account of the pituitary surgeries that Horsley performed in his private practice, La Patologia Chirurgica dell'Ipofisi (Surgical Pathology of the Hypophysis), written in 1911 by Giovanni Verga, Italian assistant professor of anatomy at the University of Pavia. They have traced the life and work of this little-known physician who contributed to the preservation of Horsley's legacy in pituitary surgery. Within Verga's pituitary treatise, a full transcription of Horsley's notes is provided for 10 pituitary cases, including the patients' clinical symptoms, surgical techniques employed, intraoperative findings, and the outcome of surgery. The descriptions of the topographical and macroscopic features of two of the lesions correspond unmistakably to the features of craniopharyngiomas, one of the squamous-papillary type and one of the adamantinomatous type. The former lesion was found on necropsy after the patient's sudden death following a temporal osteoplastic craniectomy. Surgical removal of the lesion in the latter case, with the assumed nature of an adamantinomatous craniopharyngioma, was successful. According to the

  12. Internal architecture of the proximal femur--Adam's or Adams' arch? Historical mystery.

    Science.gov (United States)

    Bartonícek, J

    2002-12-01

    The designation 'Adam Bogen' describing the thick medial cortex of the femoral neck is an incorrect term. This arch was described by Robert Adams (1795-1871), an outstanding Irish anatomist and surgeon. He was famous mainly for his book on gout and the description of disorders of cardiac rhythm, the so-called Adams-Stokes syndrome. He published his original description in the today unfortunately almost forgotten Cyclopaedia of Anatomy and Physiology, Vol. II (London, Longman, 1836-1839). The main editor of this monumental six-volume work was the famous anatomist and surgeon R.B.Todd. This book represents a significant source of information on diseases and injuries of the great joints (shoulder, elbow, wrist, knee, ankle).

  13. John Adams Lecture | 120 Years of Accelerators that Heal | 3 December

    CERN Multimedia

    2013-01-01

    120 Years of Accelerators that Heal, Dr Ugo Amaldi, Technische Universität München and TERA Foundation.     Tuesday 3 December 2013 at 2 p.m. Kjell Johnsen Auditorium, Building 30 Abstract: The discovery of X-rays was made possible by the intelligent use of the best accelerator of the time. Since then, the development of particle accelerators has been at the root of both fundamental discoveries in physics and unforeseeable medical applications. The lecture will describe the major steps in this 120-year history of diagnostics and tumour therapy. The first attempts to heal tumours with X-rays were made only one month after Röntgen’s discovery, but the understanding of the mechanisms by which the radiation kills the cells and the introduction of dose fractionation took much longer. The use of X-rays in diagnostics developed much faster and its benefits were very visible during the First World War. Today no tumour could be treated and no patient could be oper...

  14. First measurement of 153Sm in the SIR

    International Nuclear Information System (INIS)

    Michotte, C.; Ratel, G.; Lucas, L.

    1999-01-01

    In June 1998, the NIST sent to the International Reference System (SIR) a solution of 153 Sm standardized in a 4π ionization chamber. As this radionuclide had not previously been measured in the SIR, the resulting equivalent activity A e,NIST is compared with the value calculated from the efficiency curve of the SIR. However, problems occurred owing to the presence of 154 Eu and 156 Eu impurities in the solution. The manner in which the final equivalent activity value for this solution of 153 Sm has been deduced is described in this report. (authors)

  15. Preferred SH3 domain partners of ADAM metalloproteases include shared and ADAM-specific SH3 interactions.

    Directory of Open Access Journals (Sweden)

    Iivari Kleino

    Full Text Available A disintegrin and metalloproteinases (ADAMs constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3 domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior.

  16. Professor Adam Stalony-Dobrzański - the Master and the Teacher of Jerzy Nowosielski

    Directory of Open Access Journals (Sweden)

    Jarosław Szmajda

    2014-11-01

    Full Text Available When analyzing the history of Polish religious art of the XX century, we can affirm that the entire creative work of Adam Stalony-Dobrzański, professor at Kraków Academy of Fine Arts, remains in the shadow of the artistic output of Prof. Jerzy Nowosielski, his student and follower. Jerzy Nowosielski had a noticeable impact on the interest in the problems of the sacred in modern painting. The follower of Prof. Adam Stalony-Dobrzański was inspired by the art and the spirituality of Eastern Christianity. Prof. Jerzy Nowosielski filled some kind of a void in Polish religious art in the period of its evident crisis. Prof. Jerzy Nowosielski together with Prof. Adam Stalony-Dobrzański created polychrome frescoes of numerous religious buildings. The styling and the artistic accomplishments of Prof. Adam Stalony-Dobrzański are unknown for the wide audience which makes an evident gap in the history of Polish art. Polychrome frescoes and stainedglass windows can be seen in interiors of Catholic, Orthodox, and Protestant temples. The creative work of the Kraków artist is an example of the great and highly authentic vision of the sacred, which was stronger than communist censorship. The concept of Adam Stalony-Dobrzański’s art is not based on his theoretical conclusions but only on the analysis of correspondence of the artist with the then Metropolitan Archbishop of Kraków Karol Wojtyła - now St. Pope JohnPaul II. The topic of their letters was the issues of modern art and religious art, in particular the attempt to define a way in which art should be developed to meet the current needs of the Church. In contrast to the master, Prof. Adam Stalony-Dobrzański, his follower Prof. Jerzy Nowosielski has left ample commentary on his artwork. Prof. Adam Stalony-Dobrzański was rather a practitioner than a theoretician. Thus the fact of how great an impact he had on the character and the artwork of Jerzy Nowosielski is puzzling. In the first half of the

  17. Sir William Mitchell (1925-2002)

    CERN Multimedia

    2002-01-01

    Sir William (Bill) Mitchell, former President of the CERN Council, died on 30th October 2002 at the age of 77. Mitchell was professor of Physics at Oxford University from 1978 to 1989, having previously been Professor of Physics, Dean of Science and Deputy Vice-Chancellor at Reading University. From 1985 to 1990 he was Chairman of the UK's Science and Engineering Research Council (SERC), which at the time was the funding agency for the UK's participation in the CERN programme. As Chairman, Mitchell was one of the UK representatives on the CERN Council, and in 1991 he was elected President, a position he held for three years. This was a difficult period for CERN. Financial problems were being faced in many member states, notably in Germany as a result of unification. This led to calls for reductions in the CERN budget and, more significantly, to requests for delays in consderation of future programmes. On the other hand for the future of CERN and the progress of elementary particle physics, it was necessary...

  18. One day, Sir, you may tax it

    CERN Multimedia

    2011-01-01

    “One day, Sir, you may tax it”… Those are the words I used to get the audience's attention during my talk at the World Economic Forum’s annual meeting in Davos, where I was invited to speak about the science agenda in 2011. For those of you who don’t know the quote, it was Michael Faraday’s response to William Gladstone when asked to comment on the utility of his blue-sky research into the newfangled phenomenon of electricity.   So what does a 19th century English scientist have to do with the science agenda today? A great deal, I would contend. Faraday was doing basic science, but he had the foresight to realise that through applied research his findings could one day be developed into something taxable – as it turned out, electric light. Faraday had a sense of the potential of his blue-sky research, but he also appreciated that basic science alone is not enough. This was my key message in Davos. Governments often speak of ...

  19. Cellular roles of ADAM12 in health and disease

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Couchman, John R

    2008-01-01

    and it is a potential biomarker for breast cancer. It is therefore important to understand ADAM12's functions. Many cellular roles for ADAM12 have been suggested. It is an active metalloprotease, and has been implicated in insulin-like growth factor (IGF) receptor signaling, through cleavage of IGF-binding proteins......, and in epidermal growth factor receptor (EGFR) pathways, via ectodomain shedding of membrane-tethered EGFR ligands. These proteolytic events may regulate diverse cellular responses, such as altered cell differentiation, proliferation, migration, and invasion. ADAM12 may also regulate cell-cell and cell...... to or from the cell interior. These ADAM12-mediated cellular effects appear to be critical events in both biological and pathological processes. This review presents current knowledge on ADAM12 functions gained from in vitro and in vivo observations, describes ADAM12's role in both normal physiology...

  20. Demythologizing John Dewey

    Science.gov (United States)

    Bhattacharya, N. C.

    1974-01-01

    This article takes a brief but critical look at John Dewey's version of pragmatism, his contribution to philosophical scholarship generally as well as his theory and practice of liberalism. (Author/RK)

  1. Sassis tuumamajandus / John Carey

    Index Scriptorium Estoniae

    Carey, John

    2008-01-01

    USA presidendikandidaadi John McCaini energeetikakava kohaselt tuleks USA-sse ehitada 100 uut tuumaelektrijaama, neist esimesed 45 peaksid valmima aastaks 2030. Tuumaelektrijaamad aitaksid rahuldada USA energiavajadust ning võitleksid ka kliimasoojenemise vastu. Eksperdid on arengukava suhtes kriitilised

  2. Interview with John Milnor

    DEFF Research Database (Denmark)

    Raussen, Martin; Skau, Christian

    2012-01-01

    This interview was given by Professor John Milnor in connection to the Abel Prize 2011 ceremony. Originally the interview appeared in the September issue of the Newsletter of the European Mathematical Society......This interview was given by Professor John Milnor in connection to the Abel Prize 2011 ceremony. Originally the interview appeared in the September issue of the Newsletter of the European Mathematical Society...

  3. Sir Robert Sidney’s Poems Revisited: the alternative sequence

    OpenAIRE

    Relvas, Maria de Jesus C.

    1997-01-01

    The essay approaches the lyric sequence written by Sir Robert Sidney (1563-1626) in the Elizabethan age, by mainly exploring its unique formal structure, which encloses an alternative sequence formed by a re-numbering of several poems.

  4. Validation of the Spanish SIRS with monolingual Hispanic outpatients.

    Science.gov (United States)

    Correa, Amor A; Rogers, Richard; Hoersting, Raquel

    2010-09-01

    Psychologists are faced with formidable challenges in making their assessment methods relevant to growing numbers of Hispanic clients for whom English is not the primary or preferred language. Among other clinical issues, the determination of malingering has profound consequences for clients. In this investigation, we evaluated a Spanish translation of the Structured Interview of Reported Symptoms (SIRS; Rogers, Bagby, & Dickens, 1992) with 80 Spanish-speaking Hispanic American outpatients. Using a between-subjects simulation design, the Spanish SIRS was found to produce reliable results with small standard errors of measurement. Regarding validity, very large effect sizes (mean Cohen's d= 2.00) were observed between feigners and honest responders for the SIRS primary scales. We consider the potential role of the Spanish SIRS with reference to Spanish translations for other assessment instruments.

  5. Reduction of the disintegrin and metalloprotease ADAM12 in preeclampsia

    DEFF Research Database (Denmark)

    Laigaard, Jennie; Sørensen, Tina; Placing, Sophie

    2005-01-01

    OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. METHODS: We developed a semiautomated, time-resolved, immu......OBJECTIVES: The secreted form of ADAM12 is a metalloprotease that may be involved in placental and fetal growth. We examined whether the concentration of ADAM12 in first-trimester maternal serum could be used as a marker for preeclampsia. METHODS: We developed a semiautomated, time......-resolved, immunofluorometric assay for the quantification of ADAM12 in serum. The assay detected ADAM12 in a range of 78-1248 microg/L. Serum samples derived from women in the first trimester of a normal pregnancy (n = 324) and from women who later developed preeclampsia during pregnancy (n = 160) were obtained from the First...... Trimester Copenhagen Study. ADAM12 levels were assayed in these serum samples. Serum levels of ADAM12 were converted to multiples of the median (MoM) after log-linear regression of concentration versus gestational age. RESULTS: Serum ADAM12 levels in women who developed preeclampsia during pregnancy had...

  6. Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice

    Directory of Open Access Journals (Sweden)

    Ino Mitsuhiro

    2005-05-01

    Full Text Available Abstract Background ADAM22 is a member of the ADAM gene family, but the fact that it is expressed only in the nervous systems makes it unique. ADAM22's sequence similarity to other ADAMs suggests it to be an integrin binder and thus to have a role in cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM22, we employed gene targeting to generate ADAM22 knockout mice. Results ADAM22-deficient mice were produced in a good accordance with the Mendelian ratio and appeared normal at birth. After one week, severe ataxia was observed, and all homozygotes died before weaning, probably due to convulsions. No major histological abnormalities were detected in the cerebral cortex or cerebellum of the homozygous mutants; however, marked hypomyelination of the peripheral nerves was observed. Conclusion The results of our study demonstrate that ADAM22 is closely involved in the correct functioning of the nervous system. Further analysis of ADAM22 will provide clues to understanding the mechanisms of human diseases such as epileptic seizures and peripheral neuropathy.

  7. Adam Smith on public expenditure and taxation

    Directory of Open Access Journals (Sweden)

    Maurício C. Coutinho

    2001-01-01

    Full Text Available This paper presents Adam Smith’s view on taxation and public expenditure, by means of an almost literal reading of the Wealth of Nations famous passages on the "duties of the sovereign" and on the "maxims of taxation". Contrarily to the commonest usage of these passages, we will show that their core is the preoccupation with the public expenditure soaring and the defence of decentralisation. Furthermore and also contrarily to the existing interpretations we defend the non-existence of any contradiction between Smith’s income and price theory (and the incidence hypothesis, provided due attention is paid to the guiding role of the "maxims".

  8. From Adam Swift to Adam Smith: How the "Invisible Hand" Overcomes Middle Class Hypocrisy

    Science.gov (United States)

    Tooley, James

    2007-01-01

    This paper challenges Richard Pring's suggestion that parents using private education may be undermining the desire for social justice and equality, using recent arguments of Adam Swift as a springboard. Swift's position on the banning of private schools, which uses a Rawlsian "veil of ignorance" argument, is explored, and it is suggested that, if…

  9. Adam Michnik: kriisis Euroopat ohustab rahvuslik egoism / Adam Michnik ; interv. Külli-Riin Tigasson

    Index Scriptorium Estoniae

    Michnik, Adam, 1946-

    2009-01-01

    Poola suurima kvaliteetlehe Gazeta Wyborczka petoimetaja Adam Michnik vastab küsimustele, mis puudutavad 2008. aastal alanud majanduskriisi, protektsionismi ja egoismi levikut, Ida-Euroopas levinud poliitilise ja majandusliku mudeli ümber hindamist, ladinaameerikalikku putinismi ja antikommunistlikku autoritaarsust ning trükiajakirjanduse tulevikku internetiajastul. Vt. samas: Elulugu

  10. Development of Immunopathobiogenesis on SIRS-Sepsis

    Directory of Open Access Journals (Sweden)

    A Guntur Hermawan

    2009-04-01

    Full Text Available Over the past decade, sepsis has been diagnosed according to consensus guidelines established in 1991 as an infection in addition to the symptoms of systemic inflammatory response syndrome (SIRS. In addition to the previous criteria, the 2001 conference added several new diagnostic criteria for sepsis. Of particular interest was the inclusion of the biomarkers procalcitonin (PCT and C-reactive protein (CRP, despite the overall conclusion that it was premature to use biomarkers for sepsis diagnosis. The primary recommendation of the panel was the implementation of the Predisposition, insult Infection, Response, and Organ dysfunction (PIRO.The immune system has traditionally been devided into innate and adaptive components, each of which has a different role and function in defending the host against infectious agents. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also increasing evidence supports an additional critical role for TLRs in orchestrating the development of adaptive immune responses. The superantigens are able to induce toxic shock syndrome and can sometimes cause multiple organ failure via adaptive immune system. The superantigenic activity of the bacterial exotoxins can be attributed to their ability to cross-link major histocompatibility complex class II molecules on antigen-presenting cells outside the peptide groove with T-cell receptors to form a trimolecular complex. This trimolecular interaction leads to uncontrolled release of a number of proinflammatory cytokines. Proinflammatory cytokines especially IFN-γ and TNF-α, the key cytokines causing toxic shock syndrome. KEYWORDS: sepsis, innate immunity, adaptive.

  11. Commemorating John Dyson

    Science.gov (United States)

    Pittard, Julian M.

    2015-03-01

    John Dyson was born on the 7th January 1941 in Meltham Mills, West Yorkshire, England, and later grew up in Harrogate and Leeds. The proudest moment of John's early life was meeting Freddie Trueman, who became one of the greatest fast bowlers of English cricket. John used a state scholarship to study at Kings College London, after hearing a radio lecture by D. M. McKay. He received a first class BSc Special Honours Degree in Physics in 1962, and began a Ph.D. at the University of Manchester Department of Astronomy after being attracted to astronomy by an article of Zdenek Kopal in the semi-popular journal New Scientist. John soon started work with Franz Kahn, and studied the possibility that the broad emission lines seen from the Orion Nebula were due to flows driven by the photoevaporation of neutral globules embedded in a HII region. John's thesis was entitled ``The Age and Dynamics of the Orion Nebula`` and he passed his oral examination on 28th February 1966.

  12. Translating The Infinities by John Banville

    Directory of Open Access Journals (Sweden)

    Irene Abigail Piccinini

    2015-12-01

    Full Text Available Abstract - John Banville’s talent as a prose stylist is widely recognized. The polished elegance of his phrases constitutes a continuing and fascinating challenge for his translator, due to the intricacies of the source text, its manifold registers and lexical choices. In his novel The Infinities, in Italian Teoria degli Infiniti, John Banville takes cue from Kleist’s Amphytrion to devise a novel where classicality interweaves with science and science fiction through the invention of a world where the ancient gods intermingle with the humans while waiting for the death of Adam Godley, a famous mathematician who explained how an infinity of worlds exist and interact with each other. To translate this book I had not only to work extensively on lexis and style, but also to do considerable research to render the many literary and non literary references. Some examples of these struggles with the source text during the translation process are given in the present paper. Riassunto - John Banville, autore irlandese noto per la sua prosa raffinata, scrive in una lingua che rappresenta una sfida continua e affascinante per chi lo traduce. La sua complessità stilistica, che sfrutta molteplici registri linguistici e si avvale di scelte lessicali cui spesso è arduo trovare un traducente italiano soddisfacente, costringe il traduttore a fare ricorso a tutte le sottigliezze del proprio mestiere per restituire quanto più possibile l’eleganza dell’originale nella propria lingua. Nel romanzo The Infinities, tradotto in italiano come Teoria degli infiniti (Guanda, Parma 2011, Banville prende spunto dall’Anfitrione di Kleist per costruire un romanzo che guarda alla classicità sconfinando in un misto di scienza e fantascienza con la concezione di un’infinità di mondi paralleli teorizzata dal matematico Adam Godley, il protagonista morente al cui capezzale si radunano uomini e antichi dei in attesa che il cerchio della vita e della morte si compia

  13. John Deakin: Double Exposures

    Directory of Open Access Journals (Sweden)

    Paul Rousseau

    2015-11-01

    Full Text Available In this series of short films made by Jonathan Law, the art historian James Boaden, and the curator of The John Deakin Archive, Paul Rousseau, discuss the double-exposure images made by the photographer John Deakin (1912-1972 in the 1950s and 1960s. The films ask you, firstly, to look closely at the images being discussed. Each one begins with a sustained and intense shot of a single image before opening up to a wide-ranging discussion about Deakin, double exposures, and photography.

  14. John Donne no Brasil

    Directory of Open Access Journals (Sweden)

    Jose Garcez Ghirardi

    2008-04-01

    Full Text Available O leitor fica sem saber a troco do que John Donne lhe surge de repente, num virar de página, e através de períodos que parecem responder a uma pergunta que não foi formulada.(... Ninguém, nem o Sr. Afrânio Coutinho falara, até então, de John Donne,(.... Simplesmente, esse trecho, como inúmeros outros (quase todos do livro, revela que leituras apaixonantes obrigaram o professor Afrânio Coutinho a tomar em seu caderno alguns apontamentos eruditos. (MARTINS 1983 vol.I:621

  15. Lymphocyte integrin expression differences between SIRS and sepsis patients.

    Science.gov (United States)

    Heffernan, D S; Monaghan, S F; Ayala, Alfred

    2017-11-01

    Systemic Inflammatory Response Syndrome (SIRS) and sepsis remain leading causes of death. Despite many similarities, the two entities are very distinct clinically and immunologically. T-Lymphocytes play a key pivotal role in the pathogenesis and ultimately outcome following both SIRS and sepsis. Integrins are essential in the trafficking and migration of lymphocytes. They also serve vital roles in efficient wound healing and clearance of infections. Here, we investigate whether integrin expression, specifically β1 (CD29) and β2 (CD18), are disrupted in SIRS and sepsis, and assess differences in integrin expression between these two critically ill clinical categories. T-Lymphocytes were isolated from whole blood collected from ICU patients exhibiting SIRS or sepsis. Samples were analyzed for CD18 (β2) and CD29 (β1) on CD3 + T cells through flow cytometry. Septic patients were stratified into either exclusively abdominal or non-abdominal sources of sepsis. CD18 was almost ubiquitously expressed on CD3 + T cells irrespective of clinical condition. However, CD29 (β1 integrin) was lowest in SIRS patients (20.4% of CD3 + T cells) when compared with either septic patients (35.5%) or healthy volunteers (54.1%). Furthermore, there was evidence of compartmentalization in septic patients, where abdominal sources had a greater percentage of CD3 + CD29 + T cells (41.7%) when compared with those with non-abdominal sources (29.5%). Distinct differences in T-cell integrin expression exists between patients in SIRS versus sepsis, as well as relative to the source of sepsis. Further work is needed to understand cause and effect relative to the progression from SIRS into sepsis.

  16. Adams Predictor-Corrector Systems for Solving Fuzzy Differential Equations

    Directory of Open Access Journals (Sweden)

    Dequan Shang

    2013-01-01

    Full Text Available A predictor-corrector algorithm and an improved predictor-corrector (IPC algorithm based on Adams method are proposed to solve first-order differential equations with fuzzy initial condition. These algorithms are generated by updating the Adams predictor-corrector method and their convergence is also analyzed. Finally, the proposed methods are illustrated by solving an example.

  17. A brief critique of the Adam-Gibbs entropy model

    DEFF Research Database (Denmark)

    Dyre, J. C.; Hecksher, Tina; Niss, Kristine

    2009-01-01

    This paper critically discusses the entropy model proposed by Adam and Gibbs in 1965 for the dramatic temperature dependence of glass-forming liquids' average relaxation time, which is one of the most influential models during the last four decades. We discuss the Adam-Gibbs model's theoretical...

  18. Hierarchy of ADAM12 binding to integrins in tumor cells

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Fröhlich, Camilla; Nielsen, Christian Kamp

    2005-01-01

    ADAMs (a disintegrin and metalloprotease) comprise a family of cell surface proteins with protease and cell-binding activities. Using different forms and fragments of ADAM12 as substrates in cell adhesion and spreading assays, we demonstrated that alpha9beta1 integrin is the main receptor for ADA...

  19. John Cale avaldas memuaarid

    Index Scriptorium Estoniae

    1999-01-01

    Rockbändi "The Velvet Underground" asutajaliige John Cale avaldas oma autobiograafia "What's Welsh for Zen?". Koos biograafiakirjanik Victor Bockrisiga kirjutatud teos räägib 60ndate lõpu kultuurielust New Yorgis, koostööst Andy Warholiga jm.

  20. John Hennessey, Barrier Breaker

    Science.gov (United States)

    Nelson, Stephen J.

    2018-01-01

    John Hennessey lived a remarkable, full life as a professor, as a leader in his field of management and business, and moral, ethical leadership, and as dean at Dartmouth College's Tuck School of Business and provost at the University of Vermont. He was extraordinary on many fronts, a great man who lived in tumultuous times marked by world war as a…

  1. John Archibald Wheeler

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 18; Issue 1. John Archibald Wheeler - Man with Picturesque Imagination. Jayant V Narlikar. General Article Volume 18 Issue 1 January 2013 pp 22-28. Fulltext. Click here to view fulltext PDF. Permanent link:

  2. John Maynard Smith

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 11. John Maynard Smith (1920-2004). Featured Scientist Volume 10 Issue 11 November 2005 pp 110-110. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/010/11/0110-0110. Resonance ...

  3. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...

  4. Catalytic properties of ADAM12 and its domain deletion mutants

    DEFF Research Database (Denmark)

    Jacobsen, Jonas; Visse, Robert; Sørensen, Hans Peter

    2008-01-01

    of pro, catalytic, disintegrin, cysteine-rich, and EGF domains. Here we present a novel activity of recombinant ADAM12-S and its domain deletion mutants on S-carboxymethylated transferrin (Cm-Tf). Cleavage of Cm-Tf occurred at multiple sites, and N-terminal sequencing showed that the enzyme exhibits...... restricted specificity but a consensus sequence could not be defined as its subsite requirements are promiscuous. Kinetic analysis revealed that the noncatalytic C-terminal domains are important regulators of Cm-Tf activity and that ADAM12-PC consisting of the pro domain and catalytic domain is the most...... active on this substrate. It was also observed that NaCl inhibits ADAM12. Among the tissue inhibitors of metalloproteinases (TIMP) examined, the N-terminal domain of TIMP-3 (N-TIMP-3) inhibits ADAM12-S and ADAM12-PC with low nanomolar Ki(app) values while TIMP-2 inhibits them with a slightly lower...

  5. First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

    Science.gov (United States)

    Cowans, Nicholas J; Spencer, Kevin

    2007-03-01

    causing the release of free IGF for uptake into cells to promote growth. In those cases that eventually result in poor fetal growth, levels of PAPP-A and ADAM12 at 11-14 weeks are significantly lower than normal-in this instance, lowered PAPP-A and ADAM12 would result in less free IGF being available for cell uptake and growth stimulation. Further studies may elucidate if screening using such modalities can lead to new potential treatments for poorly growing fetuses. Copyright (c) 2007 John Wiley & Sons, Ltd.

  6. Adam Smith on public expenditure and taxation

    Directory of Open Access Journals (Sweden)

    Maurício C. Coutinho

    2009-05-01

    Full Text Available This paper presents Adam Smith’s view on taxation and public expenditure, by means of an almost literal reading of the Wealth of Nations famous passages on the “duties of the sovereign” and on the “maxims of taxation”. Contrarily to the commonest usage of these passages, we will show that their core is the preoccupation with the public expenditure soaring and the defence of decentralisation. Furthermore – and also contrarily to the existing interpretations – we defend the non-existence of any contradiction between Smith’s income and price theory (and the incidence hypothesis, provided due attention is paid to the guiding role of the “maxims”.

  7. John Donne no Brasil

    Directory of Open Access Journals (Sweden)

    Jose Garcez Ghirardi

    2003-04-01

    Full Text Available http://dx.doi.org/10.5007/2175-8026.2003n45p77 O leitor fica sem saber a troco do que John Donne lhe surge de repente, num virar de página, e através de períodos que parecem responder a uma pergunta que não foi formulada.(... Ninguém, nem o Sr. Afrânio Coutinho falara, até então, de John Donne,(.... Simplesmente, esse trecho, como inúmeros outros (quase todos do livro, revela que leituras apaixonantes obrigaram o professor Afrânio Coutinho a tomar em seu caderno alguns apontamentos eruditos. (MARTINS 1983 vol.I:621

  8. Oliver St John Gogarty.

    Science.gov (United States)

    Clarke, R W

    1997-01-01

    Oliver St John Gogarty--Otolaryngologist to fashionable Edwardian Dublin--was a distinguished poet and a Senator in the fledgling Irish Free State after its establishment in 1922. He numbered amongst his acquaintances the poet William Butler Yeats, the novelist James Joyce and a host of political and literary persona who helped to shape modern Ireland. He was satirised as 'stately plump Buck Mulligan' in Joyce's novel Ulysses.

  9. John Kenneth Hulm

    International Nuclear Information System (INIS)

    Hulm, J.

    1988-01-01

    John Hulm has made profound contributions to the field of superconductivity as a research scientist and as an engineer. He and his colleagues discovered the superconducting materials in commercial use today, and he played a key role in the development of commercial superconducting magnets. Dr. Hulm now serves as Chief Scientist at Westinghouse Electric Corporation. This story describes many milestones in the history of superconductivity and offers personal insight into this distinguished scientist

  10. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  11. ADAM-12 stability in first trimester maternal serum.

    Science.gov (United States)

    Cowans, N J; Stamatopoulou, A; Jaakohuhta, S; Spencer, K

    2010-06-01

    Maternal serum A Disintergrin And Metaloprotease-12 (ADAM-12) has been proposed as a marker for prenatal screening of chromosomal abnormalities, pre-eclampsia and other adverse pregnancy outcomes. In this study, we examine the stability of ADAM-12 with time and at different temperatures. Maternal serum and whole blood pools were stored at 30 degrees C, room temperature and refrigerator temperature or subjected to repeated freeze-thaw cycles. ADAM-12 was measured at set time points using an automated DELFIA research assay. Using a 10% change in concentration as a limit of stability, ADAM-12 is stable in serum for less than 15 h at 30 degrees C, less than 20 h at room temperature and for 51 h at refrigerator temperature. ADAM-12 levels are not altered following three - 20 degrees C to room temperature freeze-thaw cycles. The stability of ADAM-12 in whole blood appears similar to that in serum. The findings of this study suggest that ADAM-12 may be unstable under many routine laboratory conditions, and the marker's instability may also be partly responsible for the discrepancies in the literature.

  12. SIR-2 Data Normalization and Integration with M3 Data

    Science.gov (United States)

    Grumpe, A.; Felder, M. P.; Wöhler, C.; Mall, U.

    2013-09-01

    The point spectrometer SIR-2 on Chandrayaan-1 provided radiance spectra integrated over circular footprints of 200 m diameter in the wavelength range 934-2410.8 nm in 256 channels [1]. To analyze SIR-2 reflectance spectra in their spatial context, a coregistration to Chandrayaan-1 M³ hyperspectral images [2] as well as a correction for topography and thermal emission are inevitable. The thermal and topographic correction procedure is based on the surface temperature and a digital elevation model (DEM) inferred from M³ data. The corrected reflectance spectra are then normalized to a standard illumination and viewing geometry.

  13. The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice

    Directory of Open Access Journals (Sweden)

    Lakshini Herat

    2017-04-01

    Full Text Available Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28 appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28 mRNA and protein expression was markedly increased in the livers of mice with the metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the sympathetic nervous system, results in elevated Adam28 mRNA expression in human monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of weight gain, promotion of insulin sensitivity/glucose tolerance and decreased liver tumour necrosis factor-α (TNF-α levels in our diet-induced obesity mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also displayed reduced body weight, elevated high density lipoprotein cholesterol levels, and reductions in blood urea nitrogen, alkaline phosphatase, and aspartate aminotransferase. The results of this study provide important insights into the pathogenic role of the metalloproteinase ADAM28 in the metabolic syndrome and suggests that downregulation of ADAM28 may be a potential therapeutic strategy in the metabolic syndrome.

  14. Adam Smith and the Invisible Hand: From Metaphor to Myth

    OpenAIRE

    Gavin Kennedy

    2009-01-01

    Adam Smith and the ‘invisible hand’ are nearly synonymous in modern economic thinking. Adam Smith is strongly associated with the invisible hand, understood as a general rule that people in realising their self-interests unintentionally benefit the public good. The attribution to Smith is challengeable. Adam Smith’s use of the metaphor was much more modest; it was re-invented in the 1930s and 1940s onwards to bolster mathematical treatments of capitalism (Samuelson, Friedman) and to sup...

  15. Synthesis and immunostimulating properties of novel adamant-1-yl tripeptides.

    Science.gov (United States)

    Ribić, Rosana; Habjanec, Lidija; Vranešić, Branka; Frkanec, Ruža; Tomić, Srđanka

    2012-04-01

    The aim of this work was to prepare L- and D-(adamant-1-yl)-Gly-L-Ala-D-isoGln peptides in order to study their adjuvant (immunostimulating) activities. Adjuvant activity of adamant-1-yl tripeptides was tested in the mouse model using ovalbumin as an antigen and in comparison to the peptidoglycan monomer (PGM; β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala) and structurally related adamant-2-yl tripeptides. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  16. Research on Goods and the Ship Interaction Based on ADAMS

    Directory of Open Access Journals (Sweden)

    Song Fangzhen

    2017-01-01

    Full Text Available The equivalent method of the relative movement goods on board is discussed in details. This method is to establish dynamic model based on moving trajectory of gravity-center for goods and to take rigid body geometric model with the trajectory as constraints in ADAMS. The difference of simulation methods for the different goods in carrier rolling is compared. The interact of relative moving objects with bulk carrier is discussed by using the ADAMS model. It is verified that the ballast water can maintain the ship’s stability by means of the ADAMS model.

  17. Lance-Adams Syndrome in the Pretargeted Temperature Management Era.

    Science.gov (United States)

    Freund, Brin; Sutter, Raoul; Kaplan, Peter W

    2017-03-01

    Acute posthypoxic myoclonus portends a poor prognosis. Another form of posthypoxic myoclonus, Lance-Adams syndrome, is associated with a better outcome. Differentiating these two entities is important in prognostication and guiding further medical intervention. This can be difficult in the acute setting after hypoxic brain injury but the use of neurophysiologic studies may be helpful. In this article, we present a case of a patient who presented after pulseless electrical activity arrest, underwent targeted temperature management and subsequently developed Lance-Adams syndrome. The neurologic and electroencephalographic findings in Lance-Adams syndrome are discussed with an updated review.

  18. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...

  19. Genealogy of John and Charles Bell: their relationship with the children of Charles Shaw of Ayr.

    Science.gov (United States)

    Kaufman, M

    2005-11-01

    The Reverend William Bell had six children who survived infancy. Two of his sons entered the legal profession and two other sons became distinguished anatomists and surgeons--John Bell, said for 20 years to have been the leading operating surgeon in Britain and throughout the world--and Sir Charles Bell, possibly the most distinguished anatomist and physiologist of his day. Information is not known about the fifth son or their sister. Charles Shaw, a lawyer of Ayr, had four sons and two daughters who survived infancy. Two of his sons, John and Alexander, became anatomists and later surgeons at the Middlesex Hospital, and both worked closely with Charles Bell at the Great Windmill Street School of Anatomy. His third son entered the law and his fourth son became a distinguished soldier. The two daughters of Charles Shaw married into the Bell family: Barbara married George Joseph Bell and Marion married Mr (later Sir) Charles Bell.

  20. ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation

    DEFF Research Database (Denmark)

    Lafuste, Peggy; Sonnet, Corinne; Chazaud, Bénédicte

    2005-01-01

    of alpha9 parallels that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12 coimmunoprecipitate and participate to mpc adhesion. Inhibition of ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc fusion...

  1. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    International Nuclear Information System (INIS)

    Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning; Boehm, Beate; Pfeilschifter, Josef; Dummer, Reinhard; Mihic-Probst, Daniela; Gutwein, Paul

    2010-01-01

    Research highlights: → Strong ADAM15 expression is found in normal melanocytes. → ADAM15 expression is significantly downregulated in patients with melanoma metastasis. → TGF-β can downregulate ADAM15 expression in melanoma cells. → Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. → Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-γ and TGF-β downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  2. ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Ungerer, Christopher; Doberstein, Kai [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Buerger, Claudia; Hardt, Katja; Boehncke, Wolf-Henning [Department of Dermatology, Clinic of the Goethe-University, Theodor-Stern-Kai, Frankfurt (Germany); Boehm, Beate [Division of Rheumatology, Goethe University, Frankfurt am Main (Germany); Pfeilschifter, Josef [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany); Dummer, Reinhard [Department of Pathology, Institute of Surgical Pathology, University Hospital, Zurich (Switzerland); Mihic-Probst, Daniela [Department of Dermatology, University Hospital Zurich (Switzerland); Gutwein, Paul, E-mail: p.gutwein@med.uni-frankfurt.de [Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main (Germany)

    2010-10-22

    Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far. In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.

  3. On the Shoulders of Sir Isaac Newton and Arthur Storer

    Science.gov (United States)

    Martin, Helen E.; Evans-Gondo, Bonita

    2013-01-01

    Helen E. Martin, the author of this article, is a retired National Board Certified Teacher who has been researching Sir Isaac Newton's unpublished manuscripts for over three decades. While researching the work of Newton, a teacher she was mentoring asked for some hands-on activities to study planetary motion. The description of the activity…

  4. Sir William Jenner (1815-1898) and Queen Victoria.

    Science.gov (United States)

    Seddon, David; Queen Victoria

    2004-08-01

    This biographical note outlines the work of Sir William Jenner (1815-1898), court physician 1861-93 and President of the Royal College of Physicians 1881-8. He was the first to distinguish between typhoid and typhus both clinically and pathologically.

  5. Investigating The Travelling Wave Solution For an SIR Endemic ...

    African Journals Online (AJOL)

    This paper presents the travelling wave solution for an SIR endemic disease model with no disease related death when the spatial spread of the susceptible is not negligible. In this case the disease is driven by both the susceptible and the infective classes. The population is open since the disease is habitually prevalent in ...

  6. Buffels (Wes), Elsies, Sir Lowry's pass, Steenbras and Buffels (Oos)

    CSIR Research Space (South Africa)

    Heinecken, TJE

    1982-06-01

    Full Text Available This report is a synthesis of all available information on five of the smaller rivers discharging in to False bay combined as a single volume. The rivers dealt with are the Buffels (Wes), Elsies, Sir Lowry' Pass, Steenbras and Buffels (Oos). False...

  7. Science and controversy a biography of Sir Norman Lockyer

    CERN Document Server

    Meadows, A

    2008-01-01

    Sir Norman Lockyer left Nature, the world''s leading scientific journal, as his lasting memorial. But his life, and controversial theories, are an important part of science history. His ideas were at the forefront of public debate, and ranged from brilliant to perverse. This entertaining book is a fascinating insight into his eventful life

  8. Adam Podin ja pan-evangeelne vaimulaad / Toivo Pilli

    Index Scriptorium Estoniae

    Pilli, Toivo, 1962-

    2013-01-01

    Adam Podini elust ja tööst: Keila baptistikoguduse vaimulikuna, vanglamisjonäri ja pidalitõbiste abistajana, baptistide teoloogilise seminari direktorina, Evangeelse Alliansi kontaktisikuna Eestis

  9. Association of ADAM33 gene polymorphisms with adult-onset ...

    Indian Academy of Sciences (India)

    2011-08-19

    nucleotide ... Introduction. Asthma is a complex disease thought to arise from inter- ... The ADAM33 protein har- .... morphisms in patients and healthy controls are provided in ..... Nonetheless, meta-analyses encompassing data from.

  10. Siim Nestor soovitab : Ugly Duckling. Adam F / Siim Nestor

    Index Scriptorium Estoniae

    Nestor, Siim, 1974-

    2006-01-01

    Ameerika hip-hop-ansambli Ugly Duckling'i heliplaadi "Bang for the Buck"esitluskontserdist 9. nov. Tallinna klubis Hollywood. Inglise diskor Adam F drum'n'bass-üritusel "Sin City" 10. nov. Tartu linna klubis Tallinn

  11. Caruso St John y Robert Smithson: Interferencias

    Directory of Open Access Journals (Sweden)

    Emilia Hernández Pezzi

    2016-05-01

    Full Text Available Resumen Los discursos cruzados son el soporte común del presente número de Cuadernos. El cruce que planteamos tiene como protagonistas al artista Robert Smithson y a los arquitectos Adam Caruso y Peter St John. Estos últimos hacen mención del trabajo del artista norteamericano para explicar su proyecto de remodelación de Stortorget, la plaza de la catedral en el centro de Kalmar, Suecia. A partir de aquí, comenzamos una exploración del trabajo y las preocupaciones de ambos que nos permite dibujar convergencias y sintonías procesuales por encima de las diferencias temáticas, ideológicas y estilísticas. Al disponer en paralelo la obra de Smithson y Caruso St John descubrimos vibraciones y resonancias que muestran una interacción productiva de sus preocupaciones. La materia se convierte en sus propuestas en un objeto activo y sensible, un depósito energético con el que operar. El traslado de piedras en Stortorget convoca la memoria de la ciudad del mismo modo que el basalto y la sal del Spiral Jetty, erosionados por el tiempo, nos hablan de procesos abiertos. El tiempo y la memoria pasan a ser soportes estratégicos con los que construyen sus miradas. Los objetos se disuelven en las relaciones que establecen con su entorno produciendo equilibrios frágiles e instantáneos. De esta manera el artículo pretende generar un vórtice de reflexión, una espiral en cuyo recorrido se manifiesten las tensiones parciales del cruce propuesto, sus fijezas momentáneas.

  12. Paradise Lost Dressed in the Costume of History: John Martin’s Rendition of Paradise Lost

    Directory of Open Access Journals (Sweden)

    Laleh Atashi

    2011-01-01

    Full Text Available The story of the loss of paradise has been read and interpreted in different ages. Commentary on Milton's Paradise Lost is not limited to verbal texts; painters and illustrators have contributed greatly to the poem by presenting their own time-bound readings and interpretations of the poem through their illustrations that are far beyond mere decorations. John Martin, in the aftermath of the Industrial Revolution, deletes the Father and the Son from his illustrations. Only angels such as Raphael are the representations of deity and are as powerless and tiny as Adam and Eve. Adam and Eve, after the Fall seem as small, powerless and as subjugated to the natural surrounding as they were before the Fall. Satan is the only powerful figure in his elegant palace. Through a new historical outlook, the researchers aim at exposing the workings of ideology and dominant discourses that informed John Martin's pictorial reading of Milton's poem in the early 19th century

  13. Adams-Iwasawa N=8 Black Holes

    CERN Document Server

    Cacciatori, Sergio Luigi; Marrani, Alessio

    2012-01-01

    We study some of the properties of the geometry of the exceptional Lie group E7(7), which describes the U-duality of the N=8, d=4 supergravity. In particular, based on a symplectic construction of the Lie algebra e7(7) due to Adams, we compute the Iwasawa decomposition of the symmetric space M=E7(7)/(SU(8)/Z_2), which gives the vector multiplets' scalar manifold of the corresponding supergravity theory. The explicit expression of the Lie algebra is then used to analyze the origin of M as scalar configuration of the "large" 1/8-BPS extremal black hole attractors. In this framework it turns out that the U(1) symmetry spanning such attractors is broken down to a discrete subgroup Z_4, spoiling their dyonic nature near the origin of the scalar manifold. This is a consequence of the fact that the maximal manifest off-shell symmetry of the Iwasawa parametrization is determined by a completely non-compact Cartan subalgebra of the maximal subgroup SL(8,R) of E7(7), which breaks down the maximal possible covariance SL...

  14. Case study: adams mine landfill proposal

    International Nuclear Information System (INIS)

    Oates, L.

    2003-01-01

    I have been asked to comment on 'how to address social concerns' in my capacity as the project manager for the City of Toronto's Toronto Integrated Solid Waste Resource Management (TIRM) Process, which was initiated in 1997 and concluded in the Fall of 2000. Inherent in this request is the goal of learning from a non-nuclear procurement process in order to offer insights for those working in the field on the short- and long-term management of nuclear waste. In particular, I have been asked to comment on the learning experience from the proposed engagement of the Adams Mine Landfill that became the focus of an intense four-day debate before Toronto's City Council and was propelled into international news linked to Toronto's Olympic bid. I would like to extend my thanks to Natural Resources Canada for their support of my participation in the NEA Conference. The opinions in this paper are those of the author and not those of the City of Toronto. (author)

  15. The many ways of feeding ADAM

    International Nuclear Information System (INIS)

    Ambrosch-Draxl, C.

    2008-01-01

    Full text: The research group is dedicated to computational materials science, mostly applying and developing methods based on density functional theory (DFT). Methodological developments concern excited state properties but also the improvement of ground state calculations, both through the implementation of new functionals and the combination of DFT with manybody perturbation theory. Such a procedure may be driven by materials under investigation, which range from conventional inorganic semiconductors via organic semiconductors to complex nanostructures, and from simple metals via metal alloys to superconductors. Some of the most recent research projects are embedded into research networks, such as the NFN interface controlled and functionalized organic films, or the ERA Nanoscience Project NaPhoD - Nano-Hybrids for photonic devices. Another line of research is dedicated to metal alloys and complex interfaces, carried out within the framework of the COMET program recently established in Leoben. All this work requires high-performance computing power, which was realized in the computer cluster ADAM installed at the Montanuniversitaet. (author)

  16. ADAM SMITH: THE INVISIBLE HAND OR CONFIDENCE

    Directory of Open Access Journals (Sweden)

    Fernando Luis, Gache

    2010-01-01

    Full Text Available In 1776 Adam Smith raised the matter that an invisible hand was the one which moved the markets to obtain its efficiency. Despite in the present paper we are going to raise the hypothesis, that this invisible hand is in fact the confidence that each person feels when he is going to do business. That in addition it is unique, because it is different from the confidence of the others and that is a variable nonlinear that essentially is ligatured to respective personal histories. For that we are going to take as its bases the paper by Leopoldo Abadía (2009, with respect to the financial economy crisis that happened in 2007-2008, to evidence the form in which confidence operates. Therefore the contribution that we hope to do with this paper is to emphasize that, the level of confidence of the different actors, is the one which really moves the markets, (therefore the economy and that the crisis of the subprime mortgages is a confidence crisis at world-wide level.

  17. Who taught Adam to speak?1

    Directory of Open Access Journals (Sweden)

    Arthur C. Custance

    1994-03-01

    Full Text Available It is taken for granted that the first man, being half-ape, 'spoke’ by copying them. Research shows that such grunts and cries cannot ‘evolve' into cultured speech because the speech organs and brain structure required for human language are entirety different from those needed for of animal communication. The difference in animal and human thinking processes is not merely one of degree but rather of kind. This difference is seen in the use of signs vs. symbols, of emotional and situational language v.v. conceptual, objective language. No animal communication system can account for the human one. Perhaps, then, speech is instinctive? No, for people, however primitive, have been found without a language. Yet unless spoken to, one does not learn to speak as demonstrated by feral (wild children and deaf-mutes(like Helen Keller. So the question is - who spoke to the first human being - Adam to teach him? About all that scientific investigation can do is to demonstrate what cannot be the origin of this extraordinary trait of human nature. The only light we have is from revelation. The first two chapters of Genesis not only tell us Who spoke first but also how the process of language was acquired. But the implications of the necessity of this unique faculty in terms of his humanity and the purpose of his very creation are profound.

  18. Filsafat Multikulturalisme John Rawls

    Directory of Open Access Journals (Sweden)

    Rina Rehayati

    2012-12-01

    Full Text Available Terjadinya konflik horizontal yang mengatasnamakan identitas kelompok (etnis, suku, keyakinan dan seterusnya dikarenakan adanya phobia terhadap perbedaan. Padahal perbedaan suatu keniscayaan, karena manusia tidak akan mampu menyeragamkan atau menuntut orang lain untuk sama dengan dirinya, baik pada aspek pemikiran, keyakinan, etnis, suku, budaya, dan sebagainya. Filsafat multikulturalisme John Rawls merupakan alternatif tawaran politik kebudayaan untuk mengatasi konflik horizontal. Menurut Rawls, suatu masyarakat yang adil bukanlah hanya menjamin “the greatest happiness for the greatest number” yang selama ini terkenal dalam prinsip demokrasi. Tetapi, masyarakat yang adil menurutnya adalah adanya pengakuan dan penerimaan terhadap perbedaan dan keberagaman. Pendapatnya ini dia rangkai dalam pokok-pokok pemikirannya tentang keadilan, seperti: Justice as Fairness, Veil of Ignorance, Principle of Equal Liberty, Maximin Rule, Lexical Order dan Reflective Equilibrium.

  19. 33 CFR 147.817 - Sir Douglas Morpeth Tension Leg Platform safety zone.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Sir Douglas Morpeth Tension Leg... HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.817 Sir Douglas Morpeth Tension Leg Platform safety zone. (a) Description. The Sir Douglas Morpeth Tension Leg Platform (Morpeth...

  20. Regulating repression: roles for the sir4 N-terminus in linker DNA protection and stabilization of epigenetic states.

    Directory of Open Access Journals (Sweden)

    Stephanie Kueng

    Full Text Available Silent information regulator proteins Sir2, Sir3, and Sir4 form a heterotrimeric complex that represses transcription at subtelomeric regions and homothallic mating type (HM loci in budding yeast. We have performed a detailed biochemical and genetic analysis of the largest Sir protein, Sir4. The N-terminal half of Sir4 is dispensable for SIR-mediated repression of HM loci in vivo, except in strains that lack Yku70 or have weak silencer elements. For HM silencing in these cells, the C-terminal domain (Sir4C, residues 747-1,358 must be complemented with an N-terminal domain (Sir4N; residues 1-270, expressed either independently or as a fusion with Sir4C. Nonetheless, recombinant Sir4C can form a complex with Sir2 and Sir3 in vitro, is catalytically active, and has sedimentation properties similar to a full-length Sir4-containing SIR complex. Sir4C-containing SIR complexes bind nucleosomal arrays and protect linker DNA from nucleolytic digestion, but less effectively than wild-type SIR complexes. Consistently, full-length Sir4 is required for the complete repression of subtelomeric genes. Supporting the notion that the Sir4 N-terminus is a regulatory domain, we find it extensively phosphorylated on cyclin-dependent kinase consensus sites, some being hyperphosphorylated during mitosis. Mutation of two major phosphoacceptor sites (S63 and S84 derepresses natural subtelomeric genes when combined with a serendipitous mutation (P2A, which alone can enhance the stability of either the repressed or active state. The triple mutation confers resistance to rapamycin-induced stress and a loss of subtelomeric repression. We conclude that the Sir4 N-terminus plays two roles in SIR-mediated silencing: it contributes to epigenetic repression by stabilizing the SIR-mediated protection of linker DNA; and, as a target of phosphorylation, it can destabilize silencing in a regulated manner.

  1. ADAM, a hands-on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics.

    Science.gov (United States)

    Zuna, Ines; Holt, Andrew

    2017-11-01

    To design, construct and validate a pharmacokinetics simulator that offers students hands-on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens. The Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes. The simulator effectively models one- and two-compartment drug behaviour in a mathematically-robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve-fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported. The ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands-on pharmacokinetics learning opportunity for students that effectively complements didactic lectures. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  2. Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

    Science.gov (United States)

    Brashear, R.

    2004-12-01

    The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

  3. Sir Karl Popper and his philosophy of physics

    Science.gov (United States)

    Jammer, Max

    1991-12-01

    The eminent mathematical physicist Sir Hermann Bondi once said: “There is no more to science than its method, and there is no more to its method than Popper has said.” Indeed, many regard Sir Karl Raimund Popper the greatest philosopher of science in our generation. Much of what Popper “has said” refers to physics, but physicists, generally speaking, have little knowledge of what he has said. True, Popper's philosophy of science and, in particular, his realistic interpretation of quantum mechanics deviates considerably from the generally accepted doctrine. But as Popper, rightly I think, points out, it is precisely the proliferation of divergent theories which promotes the growth of scientific knowledge; it would be a danger for physics if physicists were dogmatically tied to a single theory or would not test their theory against alternatives. It is for this purpose that, on the occasion of the nonagenarian celebration of Popper's birthday, the present essay has been written.

  4. The susceptible-infected-recovered (SIR) model for viral marketing

    Science.gov (United States)

    Ismail, Siti Suhaila; Akil, Ku Azlina Ku; Chulan, Majdah; Sharif, Noorzila

    2017-11-01

    Viral marketing is a marketing strategy utilizes social media to spread information about a product or services provided. It is the most powerful way to share information in a short amount of time. The objective of this study is to investigate the dynamic of viral marketing within a time duration in the point of view of mathematics. This study used the epidemiological model known as Susceptible-Infected-Recovered (SIR). The model consists of a system of three differential equations with three state variables namely susceptible (S), infected (I) and recovered (R). It considers a case of SIR model with demography. Numerical experiments have been performed. The results show that viral marketing reaches its peak within two days. The online messages shared will become higher if the initial number of the infected individual has been increased.

  5. Stability analysis of the Euler discretization for SIR epidemic model

    International Nuclear Information System (INIS)

    Suryanto, Agus

    2014-01-01

    In this paper we consider a discrete SIR epidemic model obtained by the Euler method. For that discrete model, existence of disease free equilibrium and endemic equilibrium is established. Sufficient conditions on the local asymptotical stability of both disease free equilibrium and endemic equilibrium are also derived. It is found that the local asymptotical stability of the existing equilibrium is achieved only for a small time step size h. If h is further increased and passes the critical value, then both equilibriums will lose their stability. Our numerical simulations show that a complex dynamical behavior such as bifurcation or chaos phenomenon will appear for relatively large h. Both analytical and numerical results show that the discrete SIR model has a richer dynamical behavior than its continuous counterpart

  6. ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor progression

    DEFF Research Database (Denmark)

    Frohlich, Camilla; Nehammer, Camilla; Albrechtsen, Reidar

    2011-01-01

    that ADAM12 deficiency reduces breast tumor progression in the PyMT model. However, the catalytic activity of ADAM12 appears to be dispensable for its tumor-promoting effect. Interestingly, we demonstrate that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT model does not influence......Expression of ADAM12 is low in most normal tissues, but is markedly increased in numerous human cancers, including breast carcinomas. We have previously shown that overexpression of ADAM12 accelerates tumor progression in a mouse model of breast cancer (PyMT). In the present study, we found...... hypothesized, however, that the tumor-associated stroma may stimulate ADAM12 expression in tumor cells, based on the fact that TGF-ß1 stimulates ADAM12 expression and is a well-known growth factor released from tumor-associated stroma. TGF-ß1 stimulation of ADAM12-negative Lewis lung tumor cells induced ADAM12...

  7. ADAM12-S stimulates bone growth in transgenic mice by modulating chondrocyte proliferation and maturation

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Albrechtsen, Reidar; Rudkjaer, Lise

    2006-01-01

    ADAM12-S transgenic mice exhibit a pronounced increase in the length of bones, such as femur, tibia, and vertebrae. The effect of ADAM12-S on longitudinal bone growth involves the modulation of chondrocyte proliferation and maturation, likely through proteolytic activities and altered cell......: Transgenic mice expressing the secreted form of human ADAM12, ADAM12-S, or a truncated metalloprotease-deficient form of ADAM12-S in the circulation were used to study the effects of ADAM12 on the skeleton. In addition, murine chondrocyte cultures were used to study the effect of ADAM12-S on cell...... studies showed that ADAM12-S inhibits chondrocyte adhesion to fibronectin and collagen type II. CONCLUSIONS: ADAM12-S stimulates bone growth in mice by modulating chondrocyte proliferation and maturation through mechanisms probably involving both metalloprotease and adhesion activities....

  8. The Systemic Inflammatory Response Syndrome (SIRS in acutely hospitalised medical patients: a cohort study

    Directory of Open Access Journals (Sweden)

    Storgaard Merete

    2009-12-01

    Full Text Available Abstract Background Sepsis is an infection which has evoked a systemic inflammatory response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS is identified by two or more symptoms including fever or hypothermia, tachycardia, tachypnoea and change in blood leucocyte count. The relationship between SIRS symptoms and morbidity and mortality in medical emergency ward patients is unknown. Methods We conducted a prospective cohort study of the frequency of SIRS and its relationship to sepsis and death among acutely hospitalised medical patients. In 437 consecutive patients, SIRS status, blood pressure, infection and comorbidity on admission was registered together with 28-day mortality. Results A hundred and fifty-four patients (35% had SIRS on admission, 211 patients (48% had no SIRS, and 72 patients (16% had insufficient data to evaluate their SIRS status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS patients versus 41/211 non-SIRS patients: p Conclusion We found SIRS status on admission to be moderately associated with infection and strongly related to 28-day mortality.

  9. The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2011-06-09

    Abstract The ADAMs are transmembrane proteins implicated in proteolysis and cell adhesion. Forty gene members of the family have been identified, of which 21 are believed to be functional in humans. As proteases, their main substrates are the ectodomains of other transmembrane proteins. These substrates include precursor forms of growth factors, cytokines, growth factor receptors, cytokine receptors and several different types of adhesion molecules. Although altered expression of specific ADAMs has been implicated in different diseases, their best-documented role is in cancer formation and progression. ADAMs shown to play a role in cancer include ADAM9, ADAM10, ADAM12, ADAM15 and ADAM17. Two of the ADAMs, i.e., ADAM10 and 17 appear to promote cancer progression by releasing HER\\/EGFR ligands. The released ligands activate HER\\/EGFR signalling that culminates in increased cell proliferation, migration and survival. Consistent with a causative role in cancer, several ADAMs are emerging as potential cancer biomarkers for aiding cancer diagnosis and predicting patient outcome. Furthermore, a number of selective ADAM inhibitors, especially against ADAM10 and ADAM17, have been shown to have anti-cancer effects. At least one of these inhibitors is now undergoing clinical trials in patients with breast cancer.

  10. SirT1 regulates energy metabolism and response to caloric restriction in mice.

    Directory of Open Access Journals (Sweden)

    Gino Boily

    Full Text Available The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

  11. Stability and bifurcation analysis in a delayed SIR model

    International Nuclear Information System (INIS)

    Jiang Zhichao; Wei Junjie

    2008-01-01

    In this paper, a time-delayed SIR model with a nonlinear incidence rate is considered. The existence of Hopf bifurcations at the endemic equilibrium is established by analyzing the distribution of the characteristic values. A explicit algorithm for determining the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions are derived by using the normal form and the center manifold theory. Numerical simulations to support the analytical conclusions are carried out

  12. [Sir Harold Ridley--the creator of modern cataract surgery].

    Science.gov (United States)

    Obuchowska, Iwona; Mariak, Zofia

    2005-01-01

    In February 2000, the worldwide ophthalmology community celebrated the 50th anniversary of one of the twentieth century's most important innovations in eye care--the implantation of the first intraocular lens after cataract extraction by Sir Harold Ridley. It was the initiation of a golden age for the development of ophthalmology, especially cataract surgery. In our paper we would like to remember this outstanding English ophthalmologist and his great invention.

  13. Development of SIR-C Ground Calibration Equipment

    Science.gov (United States)

    Freeman, A.; Azeem, M.; Haub, D.; Sarabandi, K.

    1993-01-01

    SIR-C/X-SAR is currently scheduled for launch in April 1994. SIR-C is an L-Band and C-Band, multi-polarization spaceborne SAR system developed by NASA/JPL. X- SAR is an X-Band SAR system developed by DARA/ASI. One of the problems involved in calibrating the SIR-C instrument is to make sure that the horizontal (H) and vertical (V) polarized beams are aligned in the azimuth direction, i.e.. that they are pointing in the same direction. This is important if the polarimetric performance specifications for the system are to be met. To solve this problem, we have designed and built a prototype of a low-cost ground receiver capable of recording received power from two antennas, one H-polarized, the other V-polarized. The two signals are mixed to audio then recorded on the left and right stereo channels of a standard audio cassette player. The audio cassette recording can then be played back directly into a Macintosh computer, where it is digitized. Analysis of.

  14. ADAM 12-S cleaves IGFBP-3 and IGFBP-5 and is inhibited by TIMP-3

    DEFF Research Database (Denmark)

    Loechel, F; Fox, J W; Murphy, G

    2000-01-01

    that it cleaves insulin-like growth factor binding protein-3 (IGFBP-3). This result supports a role for ADAM 12-S in the degradation of IGFBP-3 in the blood of pregnant women. Furthermore, we tested for proteolysis of other members of the IGF binding protein family and found that ADAM 12-S cleaves IGFBP-5......ADAMs are a family of multidomain proteins having proteolytic and cell adhesion activities. We have previously shown that ADAM 12-S, the secreted soluble form of human ADAM 12, is a catalytically active protease. We now describe the purification of full-length recombinant ADAM 12-S and demonstrate...

  15. Cell-surface metalloprotease ADAM12 is internalized by a clathrin- and Grb2-dependent mechanism

    DEFF Research Database (Denmark)

    Hansen, Dorte Stautz; Leyme, Anthony; Grandal, Michael Vibo

    2012-01-01

    ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell-surface ......ADAM12 (A Disintegrin And Metalloprotease 12), a member of the ADAMs family of transmembrane proteins, is involved in ectodomain shedding, cell-adhesion and signaling, with important implications in cancer. Therefore, mechanisms that regulate the levels and activity of ADAM12 at the cell...

  16. Targeting ADAM12 in human disease: head, body or tail?

    DEFF Research Database (Denmark)

    Jacobsen, J; Wewer, U M

    2009-01-01

    ) and insulin-like growth factor receptor signaling. The body of the protein (consisting of the disintegrin, cysteine-rich, and EGF-like domains) is involved in contacts with the extracellular matrix and other cells through interactions with integrins and syndecans. Finally, the tail of the protein (consisting......ADAM12/meltrin alpha is a type I transmembrane multidomain protein involved in tumor progression and other severe diseases, including osteoarthritis, and as such could be considered as a potential drug target. In addition to protease activity, ADAM12 possesses cell binding and cell signaling...... properties. This functional trinity is reflected in the structure of ADAM12, which can be divided into head, body, and tail. The head of the protein (consisting of the pro and catalytic domains) mediates processing of growth factors and cytokines and has been implicated in epidermal growth factor (EGF...

  17. The Challenges for Sub-Saharan Africa. Sir John Crawford Memorial Lecture (1st, Washington, DC, November 1, 1985).

    Science.gov (United States)

    McNamara, Robert S.

    The economic crisis in Sub-Saharan Africa threatens to condemn an entire continent to human misery unless stronger action is taken to control population growth, reverse ecological devastation, eliminate distortions in domestic economic policies, and increase external development finance. Substantial increases in financial assistance to Africa are…

  18. Does the Leadership Style and Command Method of General Sir John Monash Remain Relevant to the Contemporary Commander?

    Science.gov (United States)

    2009-12-11

    expected to advertise the fact that the greatest strategist in the Army was a civilian when the war began, and that they were surpassed by a man who...Monash enlisted into D Company (University Company), 4th Battalion, Victorian Rifles, where he rose to the rank of Colour -Sergeant. Military service

  19. HISTORICAL NOTE JOHN HUNTER (SURGEON) John Hunter FRS ...

    African Journals Online (AJOL)

    JOHN HUNTER (SURGEON). John Hunter FRS (13 February 1728-16 October 1793) was a Scottish surgeon, one of the most distinguished scientists and surgeons of his day. He was an early advocate of careful observation and scientific method in medicine. He was the husband of Anne Hunter, a teacher, friend and ...

  20. ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer

    Science.gov (United States)

    Feldinger, Katharina; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Ng, Tzi Bun; Wong, Jack Ho; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Li, Ji-Liang; Bridges, Esther; Turley, Helen; Leek, Russell; Roxanis, Ioannis; Capala, Jacek; Murphy, Gillian; Harris, Adrian L.; Kong, Anthony

    2014-01-01

    Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p≤0.001 in BT474; p≤0.01 in SKBR3) and in vivo (p≤0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p≤0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p≤0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p≤0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients. PMID:24952873

  1. Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family MembersV⃞

    Science.gov (United States)

    Huang, Jing; Bridges, Lance C.; White, Judith M.

    2005-01-01

    A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (α4β1, α5β1, or both), and cell migration on full-length fibronectin or on its α4β1 or α5β1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the α4β1 but not the α5β1 integrin. ADAM17 had the reciprocal effect; it inhibited α5β1- but not α4β1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both α4β1 and α5β1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the α4β1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains. PMID:16079176

  2. John Locke and the case of Anthony Ashley Cooper.

    Science.gov (United States)

    Anstey, Peter R; Principe, Lawrence M

    2011-01-01

    In June 1668 Anthony Ashley Cooper, later to become the 1st Earl of Shaftesbury, underwent abdominal surgery to drain a large abscess above his liver. The case is extraordinary, not simply on account of the eminence of the patient and the danger of the procedure, but also because of the many celebrated figures involved. A trove of manuscripts relating to this famous operation survives amongst the Shaftesbury Papers in the National Archives at Kew. These include case notes in the hand of the philosopher John Locke and advice from leading physicians of the day including Francis Glisson, Sir George Ent and Thomas Sydenham. The majority of this material has never been published before. This article provides complete transcriptions and translations of all of these manuscripts, thus providing for the first time a comprehensive case history. It is prefaced with an extended introduction.

  3. Harald Velner - insener üle poole sajandi / Harald-Adam Velner

    Index Scriptorium Estoniae

    Velner, Harald-Adam, 1923-2012

    2008-01-01

    Harald-Adam Velner on Eesti Inseneride Liidu esimene taasiseseisvumisjärgne president. Lisaks Liis Seili lühiartikkel Harald-Adam Velneri isast August Velnerist: Teedeinsenerist isa juhtis inseneride ühendust enne sõda

  4. Transgenic overexpression of ADAM12 suppresses muscle regeneration and aggravates dystrophy in aged mdx mice

    DEFF Research Database (Denmark)

    Jørgensen, Louise Helskov; Jensen, Charlotte Harken; Wewer, Ulla M

    2007-01-01

    mice (ADAM12(+)) after a knife cut lesion and observed that the regeneration process was significantly impaired. ADAM12 seemed to inhibit the satellite cell response and delay myoblast differentiation. These results discourage long-term therapeutic use of ADAM12. They also point to impaired...... effect of ADAM12 was suggested to be mediated via a membrane-stabilizing up-regulation of utrophin, alpha7B integrin, and dystroglycans. Ectopic ADAM12 expression in normal mouse skeletal muscle also improved regeneration after freeze injury, presumably by the same mechanism. Hence, it was suggested...... overexpressing ADAM12 (ADAM12(+)/mdx mice), even though their utrophin levels were mildly elevated compared with age-matched controls. Thus, membrane stabilization was not sufficient to provide protection during prolonged disease. Consequently, we reinvestigated skeletal muscle regeneration in ADAM12 transgenic...

  5. ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

    OpenAIRE

    Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

    2005-01-01

    The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 d...

  6. Roles of ADAM13-regulated Wnt activity in early Xenopus eye development

    OpenAIRE

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; Nakayama, Takuya; Shah, Anoop; Grainger, Robert M.; White, Judith M.; DeSimone, Douglas W.

    2011-01-01

    Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye...

  7. An SIRS model with a nonlinear incidence rate

    International Nuclear Information System (INIS)

    Jin Yu; Wang, Wendi; Xiao Shiwu

    2007-01-01

    The global dynamics of an SIRS model with a nonlinear incidence rate is investigated. We establish a threshold for a disease to be extinct or endemic, analyze the existence and asymptotic stability of equilibria, and verify the existence of bistable states, i.e., a stable disease free equilibrium and a stable endemic equilibrium or a stable limit cycle. In particular, we find that the model admits stability switches as a parameter changes. We also investigate the backward bifurcation, the Hopf bifurcation and Bogdanov-Takens bifurcation and obtain the Hopf bifurcation criteria and Bogdanov-Takens bifurcation curves, which are important for making strategies for controlling a disease

  8. Sir Winston Churchill: treatment for pneumonia in 1943 and 1944.

    Science.gov (United States)

    Vale, J A; Scadding, J W

    2017-12-01

    This paper reviews Churchill's illnesses in February 1943 and August/September 1944 when he developed pneumonia; on the first occasion this followed a cold and sore throat. Churchill was managed at home by Sir Charles Wilson (later Lord Moran) with the assistance of two nurses and the expert advice of Dr Geoffrey Marshall, Brigadier Lionel Whitby and Colonel Robert Drew. A sulphonamide (sulphathiazole on the first occasion) was prescribed for both illnesses. Churchill recovered, and despite his illnesses continued to direct the affairs of State from his bed. On the second occasion, Churchill's illness was not made public.

  9. Sir Rudolf Peierls Selected private and scientific correspondence

    CERN Document Server

    Lee, Sabine

    2007-01-01

    This edition of the private and scientific correspondence of Sir Rudolf Peierls gives a unique insight into the life and work of one of the greatest theoretical physicists of the 20th century. Rudolf Peierls' scientific work contributed to the early developments in quantum mechanics, and he is well known and much appreciated for his contributions to various disciplines, including solid state physics, nuclear physics, and particle physics. As an enthusiastic and devoted teacher, he passed on his knowledge and understanding and inspired the work of collaborators and students alike. As an effecti

  10. Sir Ronald A. Fisher and the International Biometric Society.

    Science.gov (United States)

    Billard, Lynne

    2014-06-01

    The year 2012 marks the 50th anniversary of the death of Sir Ronald A. Fisher, one of the two Fathers of Statistics and a Founder of the International Biometric Society (the "Society"). To celebrate the extraordinary genius of Fisher and the far-sighted vision of Fisher and Chester Bliss in organizing and promoting the formation of the Society, this article looks at the origins and growth of the Society, some of the key players and events, and especially the roles played by Fisher himself as the First President. A fresh look at Fisher, the man rather than the scientific genius is also presented. © 2014, The International Biometric Society.

  11. Toward Understanding Trust: A Response to Adams and Miskell

    Science.gov (United States)

    Romero, Lisa S.; Mitchell, Douglas E.

    2018-01-01

    Purpose: Trust is a key component of successful schools. Although scholars widely agree that trust is multifaceted, there is less agreement about the number and nature of these factors. In the October 2016 issue of "Educational Administration Quarterly," C. M. Adams and Miskell (see EJ1112413) argued that their Teacher Trust of District…

  12. Adams National Historic Park Trolley Vehicle Replacement Selection Analysis

    Science.gov (United States)

    2017-12-01

    Adams NHP owns three trolley vehicles that were purchased in the early 2000s and, while their accrued mileage remains low, they have reached the end of their useful lives due in large part to vehicle parts becoming unavailable. Both the original trol...

  13. Adam Smith and the Moral Economy of the Classroom System.

    Science.gov (United States)

    Hamilton, D.

    1980-01-01

    Traces the development of mass schooling to its origins in 19th-century Glasgow. Its importance as an intellectual and economic center enabled Glasgow to invent a solution to the problem of urban schooling, while the association of scholars like Adam Smith with Glasgow University made Scottish educational theories acceptable around the world. (DB)

  14. Adam Smith and the Teaching of English Literature.

    Science.gov (United States)

    Court, Franklin E.

    1985-01-01

    Adam Smith used selections from English literature in his classroom during the eighteenth century because he believed that vernacular literature could provide a ready context for the teaching of ideological, social, and moral lessons. He believed that higher education should prepare students for the real business of the real world. (RM)

  15. The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization

    Science.gov (United States)

    van der Steen, M. C. (Marieke); Keller, Peter E.

    2013-01-01

    A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM. PMID:23772211

  16. Identification of binding peptides of the ADAM15 disintegrin domain ...

    Indian Academy of Sciences (India)

    Madhsudhan

    ADAM15 disintegrin domain (RADD) that could inhibit melanoma cell adhesion by using Escherichia coli. Second, four specific binding peptides (peptides A, B, C, and D) were selected using a phage display 12-mer peptide library. The screening protocol involved 4 rounds of positive panning on RADD and 2 rounds of ...

  17. Father Knows Best: Using Adam Smith to Teach Transactions Costs

    Science.gov (United States)

    Dupont, Brandon

    2014-01-01

    Adam Smith's moral philosophy can be used to introduce economics students to the important idea of transactions costs. The author provides a brief background in this article to Smith's moral philosophy and connects it to the costs of transacting in a way that fits easily into the standard principles of microeconomics classroom. By doing…

  18. Tuning a Le Mans Car Suspension in ADAMS

    CSIR Research Space (South Africa)

    Berman, R

    2012-09-01

    Full Text Available An ADAMS model of South Africa’s first ever Le Mans car was developed and used to tune the suspension parameters. Validation of the model is to be done by comparing simulation results to those obtained in track testing. The suspension parameters...

  19. Commentary to Adam Oliver's 'Incentivising improvements in health care delivery'

    DEFF Research Database (Denmark)

    Vrangbaek, Karsten

    2015-01-01

    The commentary discusses key issues for assessment of performance management within health care. It supports the ambition to develop more realistic understandings of performance management based on insights from behavioral economics as suggested by Adam Oliver. However, it also points to several ...

  20. Aquatic Resources of Rocky Mountain Arsenal Adams County, Colorado

    Science.gov (United States)

    1989-09-01

    Consequently, temperatures rise and oxygen levels fall. Primary producers in these stretches shift from periphyton to phytoplankton (suspended algae ...trees and have rocky substrates. Primary production in these cold- water and coolwater reaches is generally limited to periphyton (attached algae ...Adams County. Biotic components investigated included phytoplankton , zooplankton, aquatic macrophytes, benthic macroinvertebrates, fish eggs and

  1. HISTORIA ECONÓMICA: El padre de la economia: Adam Smith

    OpenAIRE

    Accensi Martínez, Maria Cinta

    2016-01-01

    Peer-reviewed Artículo que describe una pequeña bibliografía del padre de la economía Adam Smith Article que descriu una petita bibliografia sobre el pare de l'economia Adam Smith. This article include a brief bibliography about Adam Smith.

  2. ADAM 12 as a second-trimester maternal serum marker in screening for Down syndrome

    DEFF Research Database (Denmark)

    Christiansen, Michael; Spencer, Kevin; Laigaard, Jennie

    2007-01-01

    ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker...

  3. SIR-ZEE: plataforma tecnológica para el desarrollo local SIR-ZEE: technology platform for local development

    Directory of Open Access Journals (Sweden)

    Marlen Treviño Villalobos

    2012-11-01

    Full Text Available El Sistema de Información Regional de la Zona Económica Especial (SIR-ZEE nació en Costa Rica aproximadamente en 1998, cuando se concibió la idea de crear un sistema informático para recopilar, gestionar y ofrecer temáticas generadas en forma digital por diferentes entidades públicas y privadas. En el 2008, con los fondos del Programa de Regionalización Interuniversitaria del Consejo Nacional de Rectores, se aprobó la iniciativa SIR-ZEE, Plataforma Tecnológica para el Desarrollo Local, que buscó fortalecer las capacidades productivas y las capacidades de gobernabilidad en la Región Huetar Norte mediante el acceso a la información oportuna y relevante para el desarrollo económico local. Este artículo tiene como objetivo mostrar no solo la relevancia de un sistema de información en la planificación del desarrollo local, sino también que, en la actualidad, el SIR-ZEE se está convirtiendo en una ventaja competitiva para la Región Huetar Norte, ya que facilita el proceso de toma decisiones. Los principales resultados obtenidos al final de la iniciativa fueron una propuesta metodológica para la elaboración de planes estratégicos de desarrollo local en la Región Huetar Norte, la sensibilización de los actores locales sobre la participación ciudadana en las diferentes fases de la planificación, un diagnóstico territorial con el valor agregado de contar con la información georreferenciada y disponible en un sitio web, y avances en la elaboración del Plan estratégico de desarrollo local.The Regional Information System of the Special Economic Zone (SIR-ZEE was born about the year 1998 as a computer system to collect, manage and offer thematic generated in digital format by different public and private entities. In 2008, with the funds of Interuniversity Regionalization Program the National Council of Rectors approved the initiative SIR- ZEE: Platform Technology for Local Development which sought to strengthen productive

  4. A Novel Method of SIR Measurement for Power Control in CDMA Systems

    International Nuclear Information System (INIS)

    Yu, J; Wu, S B; He, J Z

    2006-01-01

    CDMA is interference limited multiple access system. Power control is an effective way to reduce co-channel interference and solve the near-far problem. Consequently, it can improve the system capacity, and make higher data rate possible. CDMA2000 employs fast closed-loop power control in reverse link to combat channel fading, and the estimation of signal to interference ratio (SIR) is required for closed-loop power control. Transmitting power is adjusted by comparing the SIR estimation with SIR target. So, it is crucial to measure the SIR of received signal accurately. Traditional measurement methods mostly depend on pilot signal strongly, when the pilots are few, there is a greater error brought to the measurement of SIR. In this paper, we discuss the SIR measurement of the received signal under the fewer pilots condition (especially only one pilot symbol) and present a novel SIR measurement method. According to the simulation, the numerical results indicate that the SIR measured by the proposed method is more accurate than the SIR measured by conventional method under fewer pilots condition

  5. Sir Victor Horsley (1857-1916): pioneer of neurological surgery.

    Science.gov (United States)

    Tan, Tze-Ching; Black, Peter McL

    2002-03-01

    Immortalized in surgical history for the introduction of "antiseptic wax," Sir Victor Horsley played a pivotal role in shaping the face of standard neurosurgical practice. His contributions include the first laminectomy for spinal neoplasm, the first carotid ligation for cerebral aneurysm, the curved skin flap, the transcranial approach to the pituitary gland, intradural division of the trigeminal nerve root for trigeminal neuralgia, and surface marking of the cerebral cortex. A tireless scientist, he was a significant player in discovering the cure for myxedema, the eradication of rabies from England, and the invention of the Horsley-Clarke stereotactic frame. As a pathologist, Horsley performed research on bacteria and edema and founded the Journal of Pathology. Horsley's kindness, humility, and generous spirit endeared him to patients, colleagues, and students. Born to privilege, he was nonetheless dedicated to improving the lot of the common man and directed his efforts toward the suffrage of women, medical reform, and free health care for the working class. Knighted in 1902 for his many contributions to medicine, Sir Victor met an untimely death during World War I from heat stroke at the age of 59. An iconoclast of keen intellect, unlimited energy, and consummate skill, his life and work justify his epitaph as a "pioneer of neurological surgery."

  6. Sir William Osler's speech at Troy: a Trojan horse?

    Science.gov (United States)

    Moran, Michael E

    2012-01-01

    Troy, New York, is a city of 55,000 people in upstate New York located along the Hudson River. A city of surprisingly rich cultural heritage, it was the home of New York state's first hospital outside New York City. The 50th anniversary celebration of Troy's hospital brought William Osler to the city as the keynote speaker. This speech, delivered on November 28, 1900, is one of Sir William's less well known addresses. Osler began his comments with Sir Thomas More's Utopia and talked at length about the hospital, its obligations, the influences it has upon the community, and the role of physicians and surgeons. He broached one of his old saws, the salary of attending physicians and their needed role in hospital management. His words were published in the diamond jubilee's records, but the hospital did not outlive its prominent guest professor, and it closed its doors in 1914. Just like the great historical city of Troy, New York's own Troy was on the brink of decline, and its hospital would be the first fatality. Therefore, it is almost prescient that the words of Osler, taken into historical context juxtaposed against the socioeconomic forces at work, are akin to the Greek's offering of a wooden edifice to end the Trojan War.

  7. Magic moments with John Bell

    Energy Technology Data Exchange (ETDEWEB)

    Bertlmann, Reinhold A.

    2015-07-15

    John Bell, with whom I had a fruitful collaboration and warm friendship, is best known for his seminal work on the foundations of quantum physics, but he also made outstanding contributions to particle physics and accelerator physics.

  8. Magic moments with John Bell

    International Nuclear Information System (INIS)

    Bertlmann, Reinhold A.

    2015-01-01

    John Bell, with whom I had a fruitful collaboration and warm friendship, is best known for his seminal work on the foundations of quantum physics, but he also made outstanding contributions to particle physics and accelerator physics

  9. American views of Sir Victor Horsley in the era of Cushing.

    Science.gov (United States)

    Lehner, Kurt R; Schulder, Michael

    2018-03-09

    Sir Victor Horsley was a pioneering British neurosurgeon known for his numerous neurosurgical, scientific, and sociopolitical contributions. Although word of these surgical and scientific achievements quickly spread throughout Europe and North America in the late 19th century, much of modern neurosurgery's view of Horsley has been colored by a single anecdote from John Fulton's biography of Harvey Cushing. In this account, Cushing observes a frenetic Horsley hastily removing a Gasserian ganglion from a patient in the kitchen of a British mansion. Not long after, Cushing left Britain saying that he had little to learn from British neurosurgery. The authors of this paper examined contemporary views of Horsley to assess what his actual reputation was in the US and Canada. The authors conducted a thorough search of references to Horsley using the following sources: American surgical and neurosurgical textbooks; major biographies; diary entries and letters; PubMed; newspaper articles; and surgical and neurosurgical texts. The positive reception of his work is corroborated by invitations for Horsley to speak in America. Research additionally revealed that Horsley had numerous personal and professional relationships with prominent Americans in medicine, including William Osler, John Wheelock Elliot, Ernest Sachs, and (yes) Harvey Cushing. Horsley's contributions to medicine and science were heavily reported in American newspapers; outside of neurosurgery, his strong opposition to the antivivisectionists and his support for alcohol prohibition were widely reported in popular media. Horsley's contributions to neurosurgery in America are undeniable. Writings from and about prominent Americans reveal that he was viewed favorably by those who had met him. Frequent publication of his views in the American media suggests that medical professionals and the public in the US valued his contributions on scientific as well as social issues. Horsley died too young, but not without the

  10. John locke on personal identity.

    Science.gov (United States)

    Nimbalkar, Namita

    2011-01-01

    John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

  11. John Locke on Personal Identity**

    OpenAIRE

    Nimbalkar, Namita

    2011-01-01

    John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

  12. Expression, purification and insights into structure and folding of the ADAM22 pro domain

    DEFF Research Database (Denmark)

    Sørensen, Hans Peter; Jacobsen, Jonas; Nielbo, Steen

    2008-01-01

    . To understand the functions of human ADAM pro domains and to determine three-dimensional structures, we have screened promising targets for expression and purification properties when using Escherichia coli as the host. The pro domain of ADAM22 (ADAM22-P) expressed in E. coli was folded, as determined by CD...... and NMR spectroscopy. An ADAM22-P fragment encoding residues 26-199 could be expressed in high amounts, remained soluble above 1 mM, and was suitable for structural studies by NMR spectroscopy. CD spectroscopy and predictions suggest that the secondary structure in ADAM22-P consists of beta...

  13. Trafficking of human ADAM 12-L: retention in the trans-Golgi network

    DEFF Research Database (Denmark)

    Hougaard, S; Loechel, F; Xu, X

    2000-01-01

    We have investigated the trafficking of the membrane-anchored form of human ADAM 12 (ADAM 12-L) fused to a green fluorescence protein tag. Subcellular localization of the protein in transiently transfected cells was determined by fluorescence microscopy and trypsin sensitivity. Full-length ADAM 12...... the cytoplasmic and transmembrane domains, but not the Src homology 3 domain (SH3) binding sites. These results raise the possibility that a trafficking checkpoint in the trans-Golgi network is one of the cellular mechanisms for regulation of ADAM 12-L function, by allowing a rapid release of ADAM 12-L...

  14. ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage

    DEFF Research Database (Denmark)

    Roy, Roopali; Wewer, Ulla M; Zurakowski, David

    2004-01-01

    -Sepharose affinity chromatography followed by protein identification by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Four peptides were identified that spanned the amino acid sequence of ADAM 12. Immunoblot analysis using ADAM 12-specific antibodies detected an approximately 68-k......Da band identified as the mature form of ADAM 12. To characterize catalytic properties of ADAM 12, full-length ADAM 12-S was expressed in COS-7 cells and purified. Substrate specificity studies demonstrated that ADAM 12-S degrades gelatin, type IV collagen, and fibronectin but not type I collagen...... or casein. Gelatinase activity of ADAM 12 was completely abrogated by zinc chelators 1,10-phenanthroline and EDTA and was partially inhibited by the hydroxamate inhibitor Marimastat. Endogenous matrix metalloprotease inhibitor TIMP-3 inhibited activity. To validate our initial identification of this enzyme...

  15. Adam8 Limits the Development of Allergic Airway Inflammation in Mice

    Science.gov (United States)

    Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

    2013-01-01

    To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

  16. Permanence for a Delayed Nonautonomous SIR Epidemic Model with Density-Dependent Birth Rate

    Directory of Open Access Journals (Sweden)

    Li Yingke

    2011-01-01

    Full Text Available Based on some well-known SIR models, a revised nonautonomous SIR epidemic model with distributed delay and density-dependent birth rate was considered. Applying some classical analysis techniques for ordinary differential equations and the method proposed by Wang (2002, the threshold value for the permanence and extinction of the model was obtained.

  17. Empathy's purity, sympathy's complexities; De Waal, Darwin and Adam Smith.

    Science.gov (United States)

    van der Weele, Cor

    2011-07-01

    Frans de Waal's view that empathy is at the basis of morality directly seems to build on Darwin, who considered sympathy as the crucial instinct. Yet when we look closer, their understanding of the central social instinct differs considerably. De Waal sees our deeply ingrained tendency to sympathize (or rather: empathize) with others as the good side of our morally dualistic nature. For Darwin, sympathizing was not the whole story of the "workings of sympathy"; the (selfish) need to receive sympathy played just as central a role in the complex roads from sympathy to morality. Darwin's understanding of sympathy stems from Adam Smith, who argued that the presence of morally impure motives should not be a reason for cynicism about morality. I suggest that De Waal's approach could benefit from a more thorough alignment with the analysis of the workings of sympathy in the work of Darwin and Adam Smith.

  18. Eclipsing Aestheticism: Western Landscape Photography After Ansel Adams

    OpenAIRE

    Dennis, Kelly

    2015-01-01

    Bien que l’héritage photographique d’Ansel Adams (1902-84) reste incontestable dans la culture de masse, dans les musées et parmi les collectionneurs, la nature de cet héritage fait débat parmi les artistes contemporains, les chercheurs et les théoriciens de la photographie. Pour certains, à la fin du 20ème siècle, les paysages typiques de Adams représentant l’Ouest américain au milieu du siècle désignaient une connivence secrète avec l’expansion américaine vers l’ouest durant la guerre froid...

  19. Dynamical Analysis of SIR Epidemic Models with Distributed Delay

    Directory of Open Access Journals (Sweden)

    Wencai Zhao

    2013-01-01

    Full Text Available SIR epidemic models with distributed delay are proposed. Firstly, the dynamical behaviors of the model without vaccination are studied. Using the Jacobian matrix, the stability of the equilibrium points of the system without vaccination is analyzed. The basic reproduction number R is got. In order to study the important role of vaccination to prevent diseases, the model with distributed delay under impulsive vaccination is formulated. And the sufficient conditions of globally asymptotic stability of “infection-free” periodic solution and the permanence of the model are obtained by using Floquet’s theorem, small-amplitude perturbation skills, and comparison theorem. Lastly, numerical simulation is presented to illustrate our main conclusions that vaccination has significant effects on the dynamical behaviors of the model. The results can provide effective tactic basis for the practical infectious disease prevention.

  20. Sir Robert Ball: Victorian Astronomer and Lecturer par excellence

    Science.gov (United States)

    Jones, R. I. G.

    2005-12-01

    Between 1875 and 1910 Sir Robert Stawell Ball gave an estimated 2,500 lectures in towns and cities all over the British Isles and abroad. This paper traces his lecturing career from its beginnings in Ireland to the triumphs of the Royal Institution, and on lecture tours in the United States of America. After a period in mathematics and mechanics, he became a populariser of science, especially astronomy, and found fame and fortune among the working classes and the aristocracy. What motivated him to tireless travels is uncertain, but it might have been that it was rewarding, financially and to his reputation. Whatever his motives, contemporary accounts are clear that BallÕs lectures were extremely popular and well-received.

  1. Microstrip Cross-coupled Interdigital SIR Based Bandpass Filter

    Directory of Open Access Journals (Sweden)

    R. K. Maharjan

    2012-09-01

    Full Text Available A simple and compact 4.9 GHz bandpass filter for C-band applications is proposed. This paper presents a novel microstrip cross-coupled interdigital half-wavelength stepped impedance resonator (SIR based bandpass filter (BPF.The designed structure is similar to that of a combination of two parallel interdigital capacitors. The scattering parameters of the structure are measured using vector network analyzer (VNA. The self generated capacitive and inductive reactances within the interdigital resonators exhibited in a resonance frequency of 4.9 GHz. The resonant frequency and bandwidth of the capacitive cross-coupled resonator is directly optimized from the physical arrangement of the resonators. The measured insertion loss (S21 and return loss (S11 were 0.3 dB and 28 dB, respectively, at resonance frequency which were almost close to the simulation results.

  2. Vaccination strategies for SIR vector-transmitted diseases.

    Science.gov (United States)

    Cruz-Pacheco, Gustavo; Esteva, Lourdes; Vargas, Cristobal

    2014-08-01

    Vector-borne diseases are one of the major public health problems in the world with the fastest spreading rate. Control measures have been focused on vector control, with poor results in most cases. Vaccines should help to reduce the diseases incidence, but vaccination strategies should also be defined. In this work, we propose a vector-transmitted SIR disease model with age-structured population subject to a vaccination program. We find an expression for the age-dependent basic reproductive number R(0), and we show that the disease-free equilibrium is locally stable for R(0) ≤ 1, and a unique endemic equilibrium exists for R(0) > 1. We apply the theoretical results to public data to evaluate vaccination strategies, immunization levels, and optimal age of vaccination for dengue disease.

  3. The Invisible Hand of God in Adam Smith

    OpenAIRE

    Denis, A.

    2005-01-01

    Adam Smith is revered as the father of modern economics. Analysis of his writings, however, reveals a profoundly medieval outlook. Smith is preoccupied with the need to preserve order in society. His scientific methodology emphasises reconciliation with the world we live in rather than investigation of it. He invokes a version of natural law in which the universe is a harmonious machine administered by a providential deity. Nobody is uncared for and, in real happiness, we are all substantiall...

  4. SIR (Safe Integral Reactor) - reducing size can reduce cost

    International Nuclear Information System (INIS)

    Hayns, M.R.

    1991-01-01

    Traditional engineering economics have favoured the advantages of larger size as a means of reducing specific capital costs and hence unit generating costs. For large and small plants utilising the same concept, e.g. a small four-loop PWR vs a large four-loop PWR with the same number of components, economies of scale are well established. If, however, a smaller plant is sized to take advantage of features which are only feasible at smaller outputs, is of simpler design, with the advantage taken of the simplified design to produce the most cost-effective layout, and incorporates fewer, more easily replaceable components with minimal assembly on site, it is possible to produce a plant which is competitive with larger plant of more traditional design. When 'system' effects, such as better matching of installed capacity to the growth in demand and the fact that a smaller total capacity will be needed to meet a given demand with a specified level of confidence, are taken into account, it can be shown that a utility's overall cash-flow position can be improved with lower associated absolute financial risks. The UK/US Safe Integral Reactor (SIR) is an integral pressurized water reactor in the 300-400 MW(e) range which utilises conventional water reactor technology in a way not feasible at the very large, sizes of recent years. The SIR concept is briefly explained and its technical and economic advantages in terms of simplicity, construction, maintenance, availability, decommissioning, safety and siting described. The results of system analyses which demonstrate the overall financial advantages to a utility are presented. (author)

  5. ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling

    DEFF Research Database (Denmark)

    Le Pabic, Hélène; Bonnier, Dominique; Wewer, Ulla M

    2003-01-01

    "A disintegrin and metalloproteinases" (ADAMs) form a family of cell-surface glycoproteins with potential protease and cell-adhesion activities. We have investigated ADAM expression in human liver cancers and their regulation by several cytokines involved in liver injury. Using degenerative RT...... carcinomas (up to 3- and 6-fold, respectively) and liver metastases from colonic carcinomas (up to 40- and 60-fold, respectively). The up-regulation of both ADAM9 and ADAM12 was correlated with an increase in matrix metalloproteinase 2 expression and activity. In conclusion, in liver cancers ADAM9 and ADAM12......-PCR, cDNA encoding sequences for ADAM9 and ADAM12 were identified in human activated hepatic stellate cells (HSCs). Northern blot analyses showed that HSCs, but not hepatocytes, expressed transcripts for ADAM9 messenger RNA (mRNA) and both the long and short forms of ADAM12. This expression...

  6. John Leask Lumley: Whither Turbulence?

    Science.gov (United States)

    Leibovich, Sidney; Warhaft, Zellman

    2018-01-01

    John Lumley's contributions to the theory, modeling, and experiments on turbulent flows played a seminal role in the advancement of our understanding of this subject in the second half of the twentieth century. We discuss John's career and his personal style, including his love and deep knowledge of vintage wine and vintage cars. His intellectual contributions range from abstract theory to applied engineering. Here we discuss some of his major advances, focusing on second-order modeling, proper orthogonal decomposition, path-breaking experiments, research on geophysical turbulence, and important contributions to the understanding of drag reduction. John Lumley was also an influential teacher whose books and films have molded generations of students. These and other aspects of his professional career are described.

  7. Titular Tilting in John Ashbery

    DEFF Research Database (Denmark)

    Balle, Søren Hattesen

    2008-01-01

    Among the numerous poems published by the American poet John Ashbery since his debut in 1956 one finds a few that specifically deal with the issue of entitlement. These poems do not appear in one single of his volumes, but are disseminated throughout Ashbery’s career and production. Their occurre......Among the numerous poems published by the American poet John Ashbery since his debut in 1956 one finds a few that specifically deal with the issue of entitlement. These poems do not appear in one single of his volumes, but are disseminated throughout Ashbery’s career and production....... Their occurrence neither follows any particular plan, nor do they form part of a larger poetic or thematic whole in the volumes where they have been published. Rather, they are perhaps better characterized as “typically atypical of Ashbery’s poetry” – to put it in paradoxical terms used by John Shoptaw in his 1994...

  8. The importance of ADAM family proteins in malignant tumors

    Directory of Open Access Journals (Sweden)

    Katarzyna Walkiewicz

    2016-02-01

    Full Text Available Increasing numbers of reports about the role of adamalysins (ADAM in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2, vascular growth factor (VEGF, tumor necrosis factor α (TNFα and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

  9. [The importance of ADAM family proteins in malignant tumors].

    Science.gov (United States)

    Walkiewicz, Katarzyna; Gętek, Monika; Muc-Wierzgoń, Małgorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa

    2016-02-11

    Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor α (TNFα) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

  10. John Theophilus Desaguliers a natural philosopher, engineer and freemason in Newtonian England

    CERN Document Server

    Carpenter, Audrey T

    2011-01-01

    John Theophilus Desaguliers made his mark on the eighteenth century in several diverse ways. He was an assistant to Sir Isaac Newton and later elucidated the difficult concepts of Newtonian physics in private lectures. He was a member of the Royal Society, and was presented with the Society's highest honour, the Copley Medal, no less than three times. He was a pioneering engineer: the water supply of Edinburgh, the ventilation of the Houses of Parliament and the first Westminster Bridge all owed him a debt. In a different sphere, Desaguliers became the third Grand Master of the Grand Lodge of

  11. The roles of ADAM33, ADAM28, IL-13 and IL-4 in the development of lung injuries in children with lethal non-pandemic acute infectious pneumonia.

    Science.gov (United States)

    Baurakiades, Emanuele; Costa, Victor Horácio; Raboni, Sonia Mara; de Almeida, Vivian Rafaela Telli; Larsen, Kelly Susana Kunze; Kohler, Juliana Nemetz; Gozzo, Priscilla do Carmo; Klassen, Giseli; Manica, Graciele C M; de Noronha, Lucia

    2014-12-01

    ADAM28, ADAM33, IL-13, IL-4 and other cytokines (IL-6 and IL-10) seem to play important roles in the persistence and maintenance of acute inflammatory processes that ultimately lead to lung remodeling and pulmonary fibrosis, which may be responsible for the high morbidity and mortality rates associated with non-pandemic acute viral pneumonias in childhood. The aim of this study was to evaluate the roles of ADAM33, ADAM28, IL4, IL6, IL10 and IL13 in the development of inflammation and alveolar fibrosis due to lethal acute respiratory infections of the lower airway in a pediatric population, especially in those with viral etiology. For this study, 193 cases were selected, and samples from the cases were processed for viral antigen detection by immunohistochemistry and then separated into two groups: virus-positive (n=68) and virus-negative (n=125). Immunohistochemistry was performed to assess the presence of metalloproteinases (ADAM33 and ADAM28) and inflammatory cytokines (IL-4, IL-13, IL-6, IL-10) in the alveolar septa. The virus-positive group showed stronger immunolabeling for ADAM33, ADAM28, IL-4 and IL-13 (pplay important roles in pulmonary inflammatory reactions elicited against etiological viral agents. In addition, these mediators may affect the process of lung remodeling and the development of pulmonary fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Roles of ADAM13-regulated Wnt activity in early Xenopus eye development

    Science.gov (United States)

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; Nakayama, Takuya; Shah, Anoop; Grainger, Robert M.; White, Judith M.; DeSimone, Douglas W.

    2012-01-01

    Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in X. tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus. PMID:22227340

  13. Control of ADAM17 activity by regulation of its cellular localisation

    Science.gov (United States)

    Lorenzen, Inken; Lokau, Juliane; Korpys, Yvonne; Oldefest, Mirja; Flynn, Charlotte M.; Künzel, Ulrike; Garbers, Christoph; Freeman, Matthew; Grötzinger, Joachim; Düsterhöft, Stefan

    2016-01-01

    An important, irreversible step in many signalling pathways is the shedding of membrane-anchored proteins. A Disintegrin And Metalloproteinase (ADAM) 17 is one of the major sheddases involved in a variety of physiological and pathophysiological processes including regeneration, differentiation, and cancer progression. This central role in signalling implies that ADAM17 activity has to be tightly regulated, including at the level of localisation. Most mature ADAM17 is localised intracellularly, with only a small amount at the cell surface. We found that ADAM17 is constitutively internalised by clathrin-coated pits and that physiological stimulators such as GPCR ligands induce ADAM17-mediated shedding, but do not alter the cell-surface abundance of the protease. In contrast, the PKC-activating phorbol ester PMA, often used as a strong inducer of ADAM17, causes not only proteolysis by ADAM17 but also a rapid increase of the mature protease at the cell surface. This is followed by internalisation and subsequent degradation of the protease. Eventually, this leads to a substantial downregulation of mature ADAM17. Our results therefore imply that physiological activation of ADAM17 does not rely on its relocalisation, but that PMA-induced PKC activity drastically dysregulates the localisation of ADAM17. PMID:27731361

  14. ADAM10 regulates Notch function in intestinal stem cells of mice.

    Science.gov (United States)

    Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

    2014-10-01

    A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. The Poetry of John Dewey

    Science.gov (United States)

    Williams, Jerry L.

    2016-01-01

    This essay examines the poetry of John Dewey, 101 poems in total. Characteristic of the rhymed and metered poetry of the period, they show a very human side of Dewey. This analysis argues that many of his poems deal with existential themes--love, finitude, and God, for example. On a deeper level these poems are also show connections to Dewey's…

  16. An Interview with John Liontas

    Science.gov (United States)

    Sadeghi, Karim

    2017-01-01

    John I. Liontas, Ph.D. is an associate professor of foreign languages, English for speakers of other languages (ESOL), and technology in education and second language acquisition (TESLA), and director and faculty of the TESLA doctoral program at the University of South Florida. Dr. Liontas is a distinguished thought leader, author, and…

  17. John Dewey, Gothic and Modern

    Science.gov (United States)

    Kaminsky, James S.

    2010-01-01

    It is argued here that understanding John Dewey's thought as that of a prodigal liberal or a fellow traveller does not capture the complexity of his work. It is also important to recognise the portion of his work that is "historie morale." In the very best sense it is epic, encapsulating the hopes and dreams of a history of the American people in…

  18. Rees, Prof. Lord Martin (John)

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1991 Honorary. Rees, Prof. Lord Martin (John) FRS. Date of birth: 23 June 1942. Address: Emeritus professor of Cosmology & Astrophysics, Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA, U.K.. Contact: Office: (+44-1223) 33 7548

  19. The Art of John Biggers

    Science.gov (United States)

    Coy, Mary

    2010-01-01

    In their 2005 exhibit of John Biggers' work, the New Orleans Museum of Art described it as being inspired by "African art and culture, the injustices of a segregated United States, the stoic women in his own family, and the heroes of everyday survival." In this article, the author describes how her students reinterpreted Biggers' work.…

  20. Dr. John Marburger visits DESY

    CERN Multimedia

    2003-01-01

    Dr. John Marburger, Director of the United States Office of Science and Technology Policy, visited the research center DESY in Hamburg. The American physicist wanted to inform himself about the status of the TESLA X-ray laser and the TESLA linear collider as well as the international collaboration at DESY (1/2 page).

  1. John Dalton (1766–1844)

    Indian Academy of Sciences (India)

    IAS Admin

    of matter and the development of science in the world, especially in. Europe. During ... He belonged to a family of Quakers. (Society of ... During this period, Dalton came under the influence of John Gough, who suggested that he maintain a ...

  2. ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

    Science.gov (United States)

    Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

    2004-01-01

    The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion. PMID:15504110

  3. Nicotinamide clearance by Pnc1 directly regulates Sir2-mediated silencing and longevity.

    Science.gov (United States)

    Gallo, Christopher M; Smith, Daniel L; Smith, Jeffrey S

    2004-02-01

    The Saccharomyces cerevisiae Sir2 protein is an NAD(+)-dependent histone deacetylase (HDAC) that functions in transcriptional silencing and longevity. The NAD(+) salvage pathway protein, Npt1, regulates Sir2-mediated processes by maintaining a sufficiently high intracellular NAD(+) concentration. However, another NAD(+) salvage pathway component, Pnc1, modulates silencing independently of the NAD(+) concentration. Nicotinamide (NAM) is a by-product of the Sir2 deacetylase reaction and is a natural Sir2 inhibitor. Pnc1 is a nicotinamidase that converts NAM to nicotinic acid. Here we show that recombinant Pnc1 stimulates Sir2 HDAC activity in vitro by preventing the accumulation of NAM produced by Sir2. In vivo, telomeric, rDNA, and HM silencing are differentially sensitive to inhibition by NAM. Furthermore, PNC1 overexpression suppresses the inhibitory effect of exogenously added NAM on silencing, life span, and Hst1-mediated transcriptional repression. Finally, we show that stress suppresses the inhibitory effect of NAM through the induction of PNC1 expression. Pnc1, therefore, positively regulates Sir2-mediated silencing and longevity by preventing the accumulation of intracellular NAM during times of stress.

  4. ADAM28 localizes to HLA-G+ trophoblasts and promotes column cell outgrowth.

    Science.gov (United States)

    De Luca, L C; Le, H T; Mara, D L; Beristain, A G

    2017-07-01

    Trophoblast progenitor cell differentiation towards the extravillous trophoblast (EVT) lineage initiates within proximal regions of anchoring columns of first trimester placental villi. While molecular processes controlling the initial stages of progenitor cell differentiation along the EVT pathway have been described, much remains unknown about factors important in distal column cell differentiation into invasive EVTs. ADAMs are proteases that regulate growth factor signaling, cell-matrix adhesion, and matrix proteolysis, and thus impact many processes relevant in placentation. Global gene expression studies identified the ADAM subtype, ADAM28, to be highly expressed in EVT-like trophoblasts, suggesting that it may play a role in EVT function. This study aims to test the functional importance of ADAM28 in column cell outgrowth and maintenance. ADAM28 mRNA levels and protein localization were determined by qPCR and immunofluorescence microscopy analyses in purified placental villi cell populations and tissues. ADAM28 function in trophoblast column outgrowth was examined using ADAM28-targetting siRNAs in Matrigel-imbedded placental explant cultures. Within placental villi, ADAM28 mRNA levels were highest in HLA-G + column trophoblasts, and consistent with this, ADAM28 was preferentially localized to HLA-G + trophoblasts within distal anchoring columns and decidual tissue. siRNA-directed loss of ADAM28 impaired trophoblast column outgrowth and resulted in increased apoptosis in matrix-invading trophoblasts. Our findings suggest that ADAM28 promotes column outgrowth by providing survival cues within anchoring column cells. This study also provides insight into a possible role for ADAM28 in driving differentiation of column trophoblasts into invasive HLA-G + EVT subsets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. SirR, a Novel Iron-Dependent Repressor in Staphylococcus epidermidis

    Science.gov (United States)

    Hill, Philip J.; Cockayne, Alan; Landers, Patrick; Morrissey, Julie A.; Sims, Catriona M.; Williams, Paul

    1998-01-01

    In Staphylococcus epidermidis and Staphylococcus aureus, a number of cell wall- and cytoplasmic membrane-associated lipoproteins are induced in response to iron starvation. To gain insights into the molecular basis of iron-dependent gene regulation in the staphylococci, we sequenced the DNA upstream of the 3-kb S. epidermidis sitABC operon, which Northern blot analysis indicates is transcriptionally regulated by the growth medium iron content. We identified two DNA sequences which are homologous to elements of the Corynebacterium diphtheriae DtxR regulon, which controls, in response to iron stress, for example, production of diphtheria toxin, siderophore, and a heme oxygenase. Upstream of the sitABC operon and divergently transcribed lies a 645-bp open reading frame (ORF), which codes for a polypeptide of approximately 25 kDa with homology to the DtxR family of metal-dependent repressor proteins. This ORF has been designated SirR (staphylococcal iron regulator repressor). Within the sitABC promoter/operator region, we also located a region of dyad symmetry overlapping the transcriptional start of sitABC which shows high homology to the DtxR operator consensus sequence, suggesting that this region, termed the Sir box, is the SirR-binding site. The SirR protein was overexpressed, purified, and used in DNA mobility shift assays; SirR retarded the migration of a synthetic oligonucleotide based on the Sir box in a metal (Fe2+ or Mn2+)-dependent manner, providing confirmatory evidence that this motif is the SirR-binding site. Furthermore, Southern blot analysis of staphylococcal chromosomal DNA with the synthetic Sir box as a probe confirmed that there are at least five Sir boxes in the S. epidermidis genome and at least three in the genome of S. aureus, suggesting that SirR controls the expression of multiple target genes. Using a monospecific polyclonal antibody raised against SirR to probe Western blots of whole-cell lysates of S. aureus, S. carnosus, S. epidermidis

  6. John von Neumann selected letters

    CERN Document Server

    2005-01-01

    John von Neuman was perhaps the most influential mathematician of the twentieth century, especially if his broad influence outside mathematics is included. Not only did he contribute to almost all branches of mathematics and created new fields, but he also changed post-World War II history with his work on the design of computers and with being a sought-after technical advisor to many figures in the U.S. military-political establishment in the 1940s and 1950s. The present volume is the first substantial collection of (previously mainly unpublished) letters written by von Neumann to colleagues, friends, government officials, and others. The letters give us a glimpse of the thinking of John von Neumann about mathematics, physics, computer science, science management, education, consulting, politics, and war. Readers of quite diverse backgrounds will find much of interest in this fascinating first-hand look at one of the towering figures of twentieth century science.

  7. Is John Locke a democrat?

    DEFF Research Database (Denmark)

    Svensson, Palle

      Over recent years there has been a tendency to present John Locke as an equalitarian democrat (Ashcraft) and being close to the political views of the levellers (Waldron). This is not a completely new interpretation (Kendall, 1941), but contrasts with the prevalent view presented in textbooks (......, criteria for a democratic process, and the institutions of polyarchy. The conclusion has implications for the relationship between political liberalism and constitutionalism on the one hand and democracy on the other....

  8. Charles Darwin and John Herschel

    Science.gov (United States)

    Warner, B.

    2009-11-01

    The influence of John Herschel on the philosophical thoughts of Charles Darwin, both through the former's book, Natural Philosophy, and through their meeting in 1836 at the Cape of Good Hope, is discussed. With Herschel having himself speculated on evolution just a few months before he met Darwin, it is probable that he stimulated at least the beginnings of the latter's lifelong work on the subject.

  9. A Conversation with John Nelder

    OpenAIRE

    Senn, Stephen

    2003-01-01

    John Ashworth Nelder was born in 1924 in Dulverton, Somerset, England. He received his secondary education in nearby Tiverton at Blundell's, a "public" [that is to say, privately funded] school that he attended as a day pupil. In 1942, he entered Sidney Sussex College, Cambridge University, to read mathematics. His studies were interrupted after one year by war service and he trained as an RAF navigator in South Africa. He returned to Cambridge in 1946 and complete his studies, graduating a "...

  10. John Glenn Biomedical Engineering Consortium

    Science.gov (United States)

    Nall, Marsha

    2004-01-01

    The John Glenn Biomedical Engineering Consortium is an inter-institutional research and technology development, beginning with ten projects in FY02 that are aimed at applying GRC expertise in fluid physics and sensor development with local biomedical expertise to mitigate the risks of space flight on the health, safety, and performance of astronauts. It is anticipated that several new technologies will be developed that are applicable to both medical needs in space and on earth.

  11. John Strong - 1941-2006

    CERN Multimedia

    2006-01-01

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on 31 July, a few days before his 65th birthday. John started his career and obtained his PhD in a group from Westfield College, initially working on experiments at Rutherford Appleton Laboratory (RAL). From the early 1970s onwards, however, his research was focused on experiments in CERN, with several particularly notable contributions. The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras (a type of television camera) to record the sparks in the spark chambers. This highly automated system allowed Omega to be used in a similar way to bubble chambers. He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems. In these experiments the Westfield group joined forces with Italian colleagues to measure the form factors of the pion and the kaon, and the lifetime of some of the newly discovered charm particles. Such h...

  12. ADAM12 overexpression does not improve outcome in mice with laminin alpha2-deficient muscular dystrophy

    DEFF Research Database (Denmark)

    Guo, Ling T; Shelton, G Diane; Wewer, Ulla M

    2005-01-01

    We have recently shown that overexpression of ADAM12 results in increased muscle regeneration and significantly reduced pathology in mdx, dystrophin deficient mice. In the present study, we tested the effect of overexpressing ADAM12 in dy(W) laminin-deficient mice. dy mice have a very severe...... clinical phenotype and would be expected to benefit greatly from enhanced regeneration. We found that dy(W) mice overexpressing ADAM12 indeed have increased muscle regeneration, as evidenced by increased numbers of muscle fibers expressing fetal myosin. However, overexpression of ADAM12 had no significant...

  13. Conservation and divergence of ADAM family proteins in the Xenopus genome

    Directory of Open Access Journals (Sweden)

    Shah Anoop

    2010-07-01

    Full Text Available Abstract Background Members of the disintegrin metalloproteinase (ADAM family play important roles in cellular and developmental processes through their functions as proteases and/or binding partners for other proteins. The amphibian Xenopus has long been used as a model for early vertebrate development, but genome-wide analyses for large gene families were not possible until the recent completion of the X. tropicalis genome sequence and the availability of large scale expression sequence tag (EST databases. In this study we carried out a systematic analysis of the X. tropicalis genome and uncovered several interesting features of ADAM genes in this species. Results Based on the X. tropicalis genome sequence and EST databases, we identified Xenopus orthologues of mammalian ADAMs and obtained full-length cDNA clones for these genes. The deduced protein sequences, synteny and exon-intron boundaries are conserved between most human and X. tropicalis orthologues. The alternative splicing patterns of certain Xenopus ADAM genes, such as adams 22 and 28, are similar to those of their mammalian orthologues. However, we were unable to identify an orthologue for ADAM7 or 8. The Xenopus orthologue of ADAM15, an active metalloproteinase in mammals, does not contain the conserved zinc-binding motif and is hence considered proteolytically inactive. We also found evidence for gain of ADAM genes in Xenopus as compared to other species. There is a homologue of ADAM10 in Xenopus that is missing in most mammals. Furthermore, a single scaffold of X. tropicalis genome contains four genes encoding ADAM28 homologues, suggesting genome duplication in this region. Conclusions Our genome-wide analysis of ADAM genes in X. tropicalis revealed both conservation and evolutionary divergence of these genes in this amphibian species. On the one hand, all ADAMs implicated in normal development and health in other species are conserved in X. tropicalis. On the other hand, some

  14. Adam Olearius ja kultuuriline Teine teekonnal Oktsidendist Orienti / Aigi Heero, Maris Saagpakk

    Index Scriptorium Estoniae

    Heero, Aigi, 1971-

    2013-01-01

    Erinevate rahvaste kujutamisest 1656. aastal ilmunud Adam Oleariuse tuntud varauusaegses reisikirjas "Vermehrte Newe Beschreibung Der Muscowitischen vnd Persischen Reyse". Eestlaste kujutamisest võrdluses teiste rahvastega

  15. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com; Wu, Yong, E-mail: wyonger@gmail.com; Wang, Bo, E-mail: wb228@126.com; Jiang, Ning, E-mail: 179639060@qq.com; Nie, Ping, E-mail: nieping1011@sina.com; Cao, Haifeng, E-mail: 0412chf@163.com; Yang, Zhi, E-mail: wcums1981@163.com; Fang, Bing, E-mail: fangbing@sjtu.edu.cn

    2016-07-08

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  16. ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

    International Nuclear Information System (INIS)

    Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

    2016-01-01

    Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.

  17. [Sir Arthur Conan Doyle, Sherlock Holmes and infectious diseases].

    Science.gov (United States)

    Ledermann D, Walter

    2010-10-01

    Besides a pleasant author of best sellers, Sir Arthur Conan Doyle was a medical doctor, writing excellent short stories about the exercise of his profession in England. However, even he mentions The British Medical Journal and The Lancet in the Sherlock Holmes's stories, when in the plot introduces infectious diseases, Conan Doyle ignores important discoveries in the field of tetanus. Anyway, the appearing of infectious diseases in the adventures of the detective are rare: one mention of tetanus, another of leprosy and- the most analyzed in medical literature a case of murder by inoculation of bacteria, probably the agent of melioidosis. Also he makes his hero discovers the toxic actions of a medusa and a transplant of solid organ. Little for a physician and less for an author who also wrote science fiction: it seems that the history of the great medical discoveries at the end of nineteenth century and beginning of the twentieth has passed by his side.., and he just couldn't see it.

  18. Italian Society of Rheumatology (SIR recommendations for performing arthrocentesis

    Directory of Open Access Journals (Sweden)

    A. Spadaro

    2011-09-01

    Full Text Available Joint fluid aspiration, or arthrocentesis, is one of the most useful and commonly performed procedures for the diagnosis and treatment of rheumatic diseases, but to date no definite guidelines have been published. For this reason, a group of experts of the Italian Society of Rheumatology (SIR produced evidence based recommendations for performing arthrocentesis. Among them, the most relevant are: a arthrocentesis is necessary when synovial effusion of unknown origin is present, especially if septic or crystal arthritis is suspected; b the patient should be clearly informed of the benefits and risks of the procedure in order to give an informed consent; c ultrasonography should be used to facilitate arthrocentesis in difficult joints; d fluid evacuation often has a therapeutic effect and facilitates the success of the following intraarticular injection; e careful skin disinfection and the use of sterile, disposable material is mandatory for avoiding septic complications. Disposable, non sterile gloves should always be used by the operator, mainly for his own protection; f contraindications are the presence of skin lesions or infections in the area of the puncture; g the patient’s anticoagulant treatment is not a contraindication, providing the therapeutic range is not exceeded; h joint rest after arthrocentesis is not indicated. Several of these recommendations were based on experts’ opinion rather than on published evidence which is scanty.

  19. Adam Smith et le “républicanisme”

    Directory of Open Access Journals (Sweden)

    Alexandra HYARD

    2003-10-01

    Full Text Available Je remercie Pierre Lurbe et Ann Thomson pour leurs remarques. Je tiens également à remercier Thierry Demals pour son aide précieuse. Néanmoins, je reste seule responsable des éventuelles erreurs contenues dans ce travail.Introduction Smith semble avoir toujours été en théorie un républicain, et il a sûrement eu le vrai esprit d’un républicain dans son amour de toute liberté rationnelle. (Rae 124 Par cette phrase, Rae nous livre son opinion sur une des questions relatives à Adam Smith (1723-1...

  20. The ADAM and EVE project: Heat transfer at ambient temperature

    International Nuclear Information System (INIS)

    Boltendahl, U.; Harth, R.

    1980-01-01

    In the nuclear research plant at Juelich a new heating system is at present being developed as part of the Nuclear Long-distance Heating Project. Helium is heated up in a high-temperature reactor. The heat chemically converts a gas mixture in a reformer plant (EVE). The gases 'charged' with energy can be transported through tubes over any distance required at ambient temperatures. In a methanisation plant (ADAM) the gases react with one another, releasing the energy in the form of heat which can be used for heating air or water. (orig.) [de

  1. Adam Smith y Sistemas Dinámicos

    Directory of Open Access Journals (Sweden)

    Osvaldo Acuña

    2008-01-01

    Full Text Available Presentamos un sistema dinámico sencillo con dos ecuaciones diferenciales, una representa la trayectoria del precio y la otra la de la cantidad de un bien en una economía. Nuestro modelo se basa sobre todo en la teoría clásica de precios expuesta por Adam Smith en La Riqueza de las Naciones. Al final del trabajo, se presenta, a modo de ejemplo, un estudio para el caso del ganado vacuno en la economía mundial.

  2. ADAMS-MATLAB Co-Simulation of A Serial Manipulator

    Directory of Open Access Journals (Sweden)

    Parthasarathy Tejaswin

    2017-01-01

    Full Text Available This paper presents the dynamic modelling and simulation of a now redundant robot, Mitsubishi RM-501, and proposes a general algorithm for experimental simulation in kinematics, dynamics and control analysis to any such robot. Through reverse engineering, a model as accurate as the real robot was developed in SolidWorks.The simulations of the same were performed in ADAMS (dynamicmodeling software offered by MSC Software Corpalong with MATLAB for motion studies and control dynamics. Finally, with a user-input path the accuracy and precision of the simulator was verified.

  3. Add-on perampanel in Lance-Adams syndrome.

    Science.gov (United States)

    Steinhoff, Bernhard J; Bacher, Matthias; Kurth, Christoph; Staack, Anke M; Kornmeier, Reinhold

    2016-01-01

    Perampanel (PER) is the first-in-class selective, noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist that has been licensed and marketed as antiepileptic drug (AED) indicated for patients with partial-onset and primary generalized tonic-clonic seizures. A positive effect was reported in some patients with epileptic myoclonic jerks in idiopathic generalized epilepsy and in progressive myoclonic epilepsy. We treated a male patient with posthypoxic nonepileptic myoclonus (Lance-Adams syndrome) with add-on PER and achieved an almost complete cessation of jerks. This effect was reproducible and, therefore, we suggest that it might be worth trying PER in comparable cases.

  4. Lance-Adams syndrome: A special case of a mother.

    Science.gov (United States)

    Nigam, Gaurav Bhaskar; Babu, Sachin Suresh; Peter, C Sudhir; Peter, C Shobhna

    2016-09-01

    Predicting the neurological outcome in survivors of cardiorespiratory arrest is difficult. A distinction has been made between acute and chronic posthypoxic myoclonus, called myoclonic status epilepticus and Lance-Adams syndrome (LAS), respectively, with the acute condition carrying a bad prognosis. Here, we report a case of a 37-year-old female who developed seizures after a successful cardiopulmonary resuscitation. The available literature on such cases is very rare and has generally mentioned a poor outcome. However, our patient was successfully managed and showed clinical features of LAS. Thus, making an early diagnosis and proper management of hypoxic brain insults is positively related to improving the patient's functional outcome.

  5. Adam Smith’s irony and the Invisible Hand

    OpenAIRE

    Cremaschi, Sergio

    2017-01-01

    I reconstruct Adam Smith’s theory of irony and its application. I illustrate how he defines it as a combination of something “grand” with something “mean” and how this is consistent with his anti-Cartesian and post-sceptic epistemology. I suggest that, for Smith, “systems” of any kind, from Cartesian physics to philosophical monotheism, Stoic ethics, and the “mercantile system” draw their apparent plausibility from some disease of human imagination. I argue that in every field, including poli...

  6. An Occupation for an Independent Gentleman - Astronomy in the Life of Herschel, John

    Science.gov (United States)

    Chapman, Allan

    Sir John Frederick William Herschel occupies a pivotal position in the history of British astronomy (1). He formed the living link between two styles or traditions of science by being the last major specimen of one breed, and the inspiration and intellectual role model for the generation that would follow. For John Herschel was perhaps the last significant figure to devote himself wholly and full-time to fundamental research in astronomy and its related sciences on the strength of a private fortune. And while the stature that he enjoyed did much to stimulate the concept of the 'professional' astronomer in Britain, so many of these men of the rising generation who admired his thorough-going dedication to science were themselves more obviously professional in the respect that they earned their livings through academic science. One sees in him, therefore, an eclectic blend of attitudes towards what science was, how it should be pursued, and how it should be paid for.

  7. The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17

    DEFF Research Database (Denmark)

    Dombernowsky, Sarah Louise; Samsøe-Petersen, Jacob; Petersen, Camilla Hansson

    2015-01-01

    The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release....... PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways. Interestingly, Pacs2-deficient mice display significantly reduced...

  8. Sir James Paget: Paget's disease of the nipple, Paget's disease of bone.

    Science.gov (United States)

    Ellis, Harold

    2013-04-01

    Sir James Paget was one of the 'great' Victorians. Eminent as a surgeon, pathologist and teacher, his nobility of character and application to his work made him a leader in his profession in that age of great men.

  9. SIR-A views our environment An Experiment in the Batu Angkal Area, West Kalimantan, Indonesia

    Directory of Open Access Journals (Sweden)

    Sutanto .

    2013-07-01

    Factors affecting the ease of identification are. mainly tonal contrast, shape, size, surface roughness, direction in relation to the illumination, and dielectric constant. Due to the future availability of SIR-B image of Kalimantan, further study is recommended.

  10. Identifying settlements on the SIR-B images of Rimbobujang and the surrounding areas, Sumatra, Indonesia

    Directory of Open Access Journals (Sweden)

    Sutanto .

    2013-07-01

    SIR-B image proves to be a reasonably good tool to identify rural settlement in an open area, especially for that with high density of houses. Its use to identify towns and cities is more recommended.

  11. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    Directory of Open Access Journals (Sweden)

    de Souza Emanuel M

    2009-03-01

    Full Text Available Abstract Background ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. Methods First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP. Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. Results The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM; tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC was 76.2% compared with 25.5% in invasive ductal carcinoma

  12. ADAM33 gene silencing by promoter hypermethylation as a molecular marker in breast invasive lobular carcinoma

    International Nuclear Information System (INIS)

    Seniski, Gerusa G; Zanata, Silvio M; Costa, Fabrício F; Klassen, Giseli; Camargo, Anamaria A; Ierardi, Daniela F; Ramos, Edneia AS; Grochoski, Mariana; Ribeiro, Enilze SF; Cavalli, Iglenir J; Pedrosa, Fabio O; Souza, Emanuel M de

    2009-01-01

    ADAM33 protein is a member of the family of transmembrane glycoproteins composed of multidomains. ADAM family members have different activities, such as proteolysis and adhesion, making them good candidates to mediate the extracellular matrix remodelling and changes in cellular adhesion that characterise certain pathologies and cancer development. It was reported that one family member, ADAM23, is down-regulated by promoter hypermethylation. This seems to correlate with tumour progression and metastasis in breast cancer. In this study, we explored the involvement of ADAM33, another ADAM family member, in breast cancer. First, we analysed ADAM33 expression in breast tumour cell lines by RT-PCR and western blotting. We also used 5-aza-2'-deoxycytidine (5azadCR) treatment and DNA bisulphite sequencing to study the promoter methylation of ADAM33 in breast tumour cell lines. We evaluated ADAM33 methylation in primary tumour samples by methylation specific PCR (MSP). Finally, ADAM33 promoter hypermethylation was correlated with clinicopathological data using the chi-square test and Fisher's exact test. The expression analysis of ADAM33 in breast tumour cell lines by RT-PCR revealed gene silencing in 65% of tumour cell lines. The corresponding lack of ADAM33 protein was confirmed by western blotting. We also used 5-aza-2'-deoxycytidine (5-aza-dCR) demethylation and bisulphite sequencing methodologies to confirm that gene silencing is due to ADAM33 promoter hypermethylation. Using MSP, we detected ADAM33 promoter hypermethylation in 40% of primary breast tumour samples. The correlation between methylation pattern and patient's clinicopathological data was not significantly associated with histological grade; tumour stage (TNM); tumour size; ER, PR or ERBB2 status; lymph node status; metastasis or recurrence. Methylation frequency in invasive lobular carcinoma (ILC) was 76.2% compared with 25.5% in invasive ductal carcinoma (IDC), and this difference was

  13. John W. Daly - An Appreciation

    Science.gov (United States)

    Kirk, Kenneth L.

    2015-01-01

    John W. Daly was engaged in groundbreaking basic research for nearly 50 years at NIH in Bethesda, Maryland. A primary focus of his research included the discovery, structure elucidation, synthesis and pharmacology of alkaloids and other biologically active natural products. However, he earned further acclaim in other areas that included the investigation of the structure-activity relationships for agonists/antagonists at adenosine, adrenergic, histamine, serotonin, and acetylcholine receptors. In addition he was a pioneer in studies of the modulation and functional relationships for systems involving calcium, cyclic nucleotides, ion channels and phospholipids and in the mechanism of actions of caffeine and other xanthines. PMID:26160996

  14. A tribute to John Gibbon.

    Science.gov (United States)

    Church, Russell M.

    2002-04-28

    This article provides an overview of the published research of John Gibbon. It describes his experimental research on scalar timing and his development of scalar timing theory. It also describes his methods of research which included mathematical analysis, conditioning methods, psychophysical methods and secondary data analysis. Finally, it describes his application of scalar timing theory to avoidance and punishment, autoshaping, temporal perception and timed behavior, foraging, circadian rhythms, human timing, and the effect of drugs on timed perception and timed performance of Parkinson's patients. The research of Gibbon has shown the essential role of timing in perception, classical conditioning, instrumental learning, behavior in natural environments and in neuropsychology.

  15. Levatiracetam for the management of Lance-Adams syndrome.

    Science.gov (United States)

    Ilik, Faik; Kemal Ilik, Mustafa; Cöven, Ilker

    2014-01-01

    Chronic post-hypoxic myoclonus, also known as Lance-Adams syndrome (LAS) is a neurological complication characterized by uncontrolled myoclonic jerks following cardiac arrest. In this article, clinical manifestation and symptomatic treatment options are discussed especially concerning the rationale of use of levatiracetam in patients with Lance-Adams syndrome. Clinical presentation is action myoclonus associated with cerebellar ataxia, postural imbalance, and very mild intellectual deficit. An 18-year-old female patient was admitted to our intensive care unit in a coma. She had a cardiorespiratory arrest after a splenectomy in a local hospital. Then, myoclonic movements were continuously observed over the entire body, including the face. On day 14 of hospitalization, we started levatiracetam 1000 mg daily. The frequency of convulsion movements was reduced. The patient level of consciousness was 15 on the Glasgow coma scale (GCS) on the Mini-Mental State Examination (MMSE) score was 23 out of 30. She was later transferred to the rehabilitation department. Vigilance is required to ensure early diagnosis and timely intervention for the myoclonic jerks. We would like to emphasize that LAS should be considered in patients with the myoclonic jerks following cardiac arrest and that levatiracetam therapy may be useful as treatment.

  16. The futility of utility: how market dynamics marginalize Adam Smith

    Science.gov (United States)

    McCauley, Joseph L.

    2000-10-01

    Economic theorizing is based on the postulated, nonempiric notion of utility. Economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics I show the following. A utility function generally does not exist mathematically due to nonintegrable dynamics when production/investment are accounted for, resolving Mirowski's thesis. Price as a function of demand does not exist mathematically either. All equilibria are unstable. I then explain how deterministic chaos can be distinguished from random noise at short times. In the generalization to liquid markets and finance theory described by stochastic excess demand dynamics, I also show the following. Market price distributions cannot be rescaled to describe price movements as ‘equilibrium’ fluctuations about a systematic drift in price. Utility maximization does not describe equilibrium. Maximization of the Gibbs entropy of the observed price distribution of an asset would describe equilibrium, if equilibrium could be achieved, but equilibrium does not describe real, liquid markets (stocks, bonds, foreign exchange). There are three inconsistent definitions of equilibrium used in economics and finance, only one of which is correct. Prices in unregulated free markets are unstable against both noise and rising or falling expectations: Adam Smith's stabilizing invisible hand does not exist, either in mathematical models of liquid market data, or in real market data.

  17. John Donne no Brasil John Donne no Brasil

    Directory of Open Access Journals (Sweden)

    Jose Garcez Ghirardi

    2008-04-01

    Full Text Available O leitor fica sem saber a troco do que John Donne lhe surge de repente, num virar de página, e através de períodos que parecem responder a uma pergunta que não foi formulada.(... Ninguém, nem o Sr. Afrânio Coutinho falara, até então, de John Donne,(.... Simplesmente, esse trecho, como inúmeros outros (quase todos do livro, revela que leituras apaixonantes obrigaram o professor Afrânio Coutinho a tomar em seu caderno alguns apontamentos eruditos. (MARTINS 1983 vol.I: 621 A citação acima, extraída de um artigo de Wilson Martins (in O Estado de São Paulo, 25/02/54, ilustra bem a posição reservada a John Donne, até então, por aqueles que, no Brasil, se dedicavam aos estudos de literatura. “A troco do que” - perguntava o autor - deveria ser o leitor de Correntes Cruzadas confrontado com o nome de Donne? Quem, até aquele momento, dele se ocupara? Ninguém, respondia o erudito articulista (nem mesmo o Sr. Afrânio Coutinho, embora reconhecendo que o nome do poeta pudesse ter sido fonte de algumas “leituras apaixonantes” . Interessava-lhe apontar enfaticamente, porém, que a lembrança de Donne surgia de maneira gratuita, desligada de qualquer argumentação ou contexto que a preparas se ou justificasse. Não apenas Afrânio Coutinho silenciara sobre a obra de Donne em seu livro; ninguém, de fato, havia, até aquele momento, dedicado, ao poeta, qualquer atenção mais demorada. Curiosamente, o próprio artigo, assim como o livro nele discutido, atestava, no entanto, que o esquecimento do nome de Donne estava por findar.

  18. Scientific objectives and selection of targets for the SMART-1 Infrared Spectrometer (SIR)

    Science.gov (United States)

    Basilevsky, A. T.; Keller, H. U.; Nathues, A.; Mall, U.; Hiesinger, H.; Rosiek, M.

    2004-12-01

    The European SMART-1 mission to the Moon, primarily a testbed for innovative technologies, was launched in September 2003 and will reach the Moon in 2005. On board are several scientific instruments, including the point-spectrometer SMART-1 Infrared Spectrometer (SIR). Taking into account the capabilities of the SMART-1 mission and the SIR instrument in particular, as well as the open questions in lunar science, a selection of targets for SIR observations has been compiled. SIR can address at least five topics: (1) Surface/regolith processes; (2) Lunar volcanism; (3) Lunar crust structure; (4) Search for spectral signatures of ices at the lunar poles; and (5) Ground truth and study of geometric effects on the spectral shape. For each topic we will discuss specific observation modes, necessary to achieve our scientific goals. The majority of SIR targets will be observed in the nadir-tracking mode. More than 100 targets, which require off-nadir pointing and off-nadir tracking, are planned. It is expected that results of SIR observations will significantly increase our understanding of the Moon. Since the exact arrival date and the orbital parameters of the SMART-1 spacecraft are not known yet, a more detailed planning of the scientific observations will follow in the near future.

  19. Occupational exposure following Yttrium-90 microspheres SIR therapy

    International Nuclear Information System (INIS)

    Fontaine, P.; Boirie, G.; Dieudonne, A.; Leguludec, D.; Lebtahi, R.; Ben Reguiga, M.

    2015-01-01

    Full text of publication follows. Introduction: Selective Internal Radiation Therapy (SIRT) is a promising technique for solid hepatic neoplasms treatment. SIRT consists in implanting radioactive microspheres (RMS) in targeted hepatic lesions via femoral artery. Two RMS-Therapsheres [glass-microspheres/TSR] and Sir-Spheres [resin-spheres/SSR]- are marketed in the European market, both radiolabeled with Yttrium-90. The objective of this study is to assess occupational exposure for nuclear medicine, radiology and clinical staff involved in Y 90 -RMS preparation and implantation. Materials and methods: The study was conducted on 20 patients treated for Hepato-Cellular Carcinoma: 10 treated with TSR and 10 with SSR. Dose rate (DR, mSv/h) or absorbed doses (mSv) measurements were made during all steps of TSR and SSR handling: sources receipt and unpacking, preparation, transport to radiology, implantation, and patient care. Measurements were made with portable ionization chamber(Babyline/Nardeux), spectrometer(FieldSpect/Aries), digital dosimeter (NED/Unfors) and operational dosimeter (Mk2/Siemens). Values were expressed as mean±SD. Results: patients received of 1.8 GBq to 3.1 GBq of TSR and 0.55 GBq to 2.4 GBq of SSR. TSR were delivered ready-to-use with the prescribed activity. For SSR only one activity was commercially available and shipped (3 GBq at calibration-time)requiring a preparation step to adjust needed activity. DR measured during RMS was 1723 ± 157 μSv/h SSR and 1189 ± 92 μSv/h for TSR. When preparing spheres in radiopharmacy, fingers and whole body doses were respectively 8326 ± 2360 μSv and 12.3 ± 5,2 μSv for Sir-Spheres vs. 33.5 ± 7.8 μSv and 1.1 ± 0.3 μSv for TSR. DR in contact with carrying case during RMS transfer to radiology were 299 ± 102 μSv/h for SSR and 5.3 ± 1.2 μSv/h for TSR. During RMS infusion, radiologist's finger doses were limited to 3.6 ± 1 μSv for SSR and 0.7± 0.3 μSv for TSR. Finally, following RMS

  20. John Stuart Mill, innate differences, and the regulation of reproduction.

    Science.gov (United States)

    Paul, Diane B; Day, Benjamin

    2008-06-01

    In this paper, we show that the question of the relative importance of innate characteristics and institutional arrangements in explaining human difference was vehemently contested in Britain during the first half of the nineteenth century. Thus Sir Francis Galton's work of the 1860s should be seen as an intervention in a pre-existing controversy. The central figure in these earlier debates-as well as many later ones-was the philosopher and economist John Stuart Mill. In Mill's view, human nature was fundamentally shaped by history and culture, factors that accounted for most mental and behavioral differences between men and women and among people of different classes, nationalities, and races. Indeed, Mill's whole program of social reform depended on the assumption that human differences were not fixed by nature. To identify the leading figures in these disputes about difference and the concrete context in which they occurred, we explore three debates in which Mill played a key role: over the capacities and rights of women, the viability of peasant proprietorship in India and Ireland, and the status of black labor in Jamaica. The last two draw our attention to the important colonial context of the nature-nurture debate. We also show that ideas that for us seem of a piece were not always linked for these earlier thinkers, nor did views on innateness necessarily have the political correlates that we now take for granted.

  1. The neurological legacy of John Russell Reynolds (1828-1896).

    Science.gov (United States)

    Eadie, M J

    2007-04-01

    Sir John Russell Reynolds was an eminent and highly influential physician in the Victorian era who held the Presidencies of the Royal College of Physicians of London, and of the British Medical Association. He was the protégée of the great experimental physiologist, Marshall Hall, who discovered the reflex arc, and succeeded to Hall's clinical practice in London. Reynolds' thought and clinical activities linked the emerging British neurology of the first half of the 19th century with its blossoming, particularly in London, from 1860 onwards. In his writings Reynolds was the first English author to apply the approach to classification of neurological disorders that is still often used, though now in modified form. He was also the first to enunciate the notion of positive and negative symptoms arising from neurological disease and to suggest their pathogenesis, and was arguably the originator of the influential concept that an idiopathic disease, epilepsy, existed, one to be distinguished from 'epileptiform' seizures due to brain pathology.

  2. John Strong 1941-2006

    CERN Multimedia

    2006-01-01

    John started his career and obtained his PhD in a group from Westfield College, initially working on experiments at Rutherford Appleton Laboratory (RAL). From the early 1970s onwards, however, his research was focused on experiments in CERN, with several particularly notable contributions. The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon Cameras (a type of television camera) to record the sparks in the spark chambers. This highly automated system allowed Omega to be used in a similar way to bubble chambers.  He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems. In these experiments the Westfield group joined forces with Italian colleagues to measure the form factors of the pion and the kaon, and the lifetime of some of the newly discovered charm particles. Such has been the lasting impact of these measurements that the paper on the pion form-factor had been cited 323 times up to the time of J...

  3. John Greenleaf's life of science.

    Science.gov (United States)

    Watenpaugh, Donald E

    2012-12-01

    This article summarizes the life and career of John E. Greenleaf, PhD. It complements an interview of Dr. Greenleaf sponsored by the American Physiological Society Living History Project found on the American Physiological Society website. Dr. Greenleaf is a "thought leader" and internationally renowned physiologist, with extensive contributions in human systems-level environmental physiology. He avoided self-aggrandizement and believed that deeds rather than words define one's legacy. Viewed another way, however, Greenleaf's words define his deeds: 48% of his 185 articles are first author works, which is an unusually high proportion for a scientist of his stature. He found that writing a thorough and thoughtful discussion section often led to novel ideas that drove future research. Beyond Greenleaf's words are the many students, postdocs, and collaborators lucky enough to have worked with him and thus learn and carry on his ways of science. His core principles included the following: avoid research "fads," embrace diversity, be the first subject in your own research, adhere to rules of fiscal responsibility, and respect administrative forces-but never back down from them when you know you are right. Greenleaf's integrity ensured he was usually right. He thrived on the axiom of many successful scientists: avoid falling in love with hypotheses, so that when unexpected findings appear, they arouse curiosity instead of fear. Dr. Greenleaf's legacy will include the John and Carol Greenleaf Award for prolific environmental and exercise-related publication in the Journal of Applied Physiology.

  4. Microautoradiography of [{sup 123}I]ADAM in mice treated with fluoxetine and serotonin reuptake inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Ye, X.-X.; Chen, J.-C.; Liu, R.-S.; Wey, S.-P.; Lee, J.-S.; Chen, C.-C.; Fu, Y.-K.; Ting, Gann; Hwang, J.-J. E-mail: jjhwang@ym.edu.tw

    2004-07-01

    A radiopharmaceutical, {sup 123}I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([{sup 123}I]ADAM), has been developed recently for evaluation of how serotonin transporters (SERT) function in the brain. However, the detailed biodistribution and specific binding in certain brain areas are not well investigated. In this study, both phosphor plate imaging and microautoradiography were applied to explore the binding characteristics of [{sup 123}I]ADAM in SERT neurons. The effect of two psychotropics and one narcotic on the binding of [{sup 123}I]ADAM to SERT was also studied. Fluoxetine and desipramine, both are psychotropics and specific SERT ligands and decreased the affinity of [{sup 123}I]ADAM, while p-chloroamphetamine (PCA), a narcotic, destroyed most of serotonergic neurons, as well as reducing the concentration of serotonin and the number of SERT in the brain as shown by the biodistribution of [{sup 123}I]ADAM. Significant and selective accumulation of [{sup 123}I]ADAM in the areas from midbrain to brain stem in normal mice with maximum target-to-background ratio was found at 90 minutes postinjection. A rapid clearance of [{sup 131}I]ADAM at 120 minutes postinjection was found in the CA1, CA3 and ThN brain areas. In addition, the inhibition effect on binding ability of [{sup 123}I]ADAM to SERT by the psychotropics and the narcotic was found to have the order of: PCA > fluoxetine > desipramine.

  5. Microautoradiography of [123I]ADAM in mice treated with fluoxetine and serotonin reuptake inhibitors

    International Nuclear Information System (INIS)

    Ye, X.-X.; Chen, J.-C.; Liu, R.-S.; Wey, S.-P.; Lee, J.-S.; Chen, C.-C.; Fu, Y.-K.; Ting, Gann; Hwang, J.-J.

    2004-01-01

    A radiopharmaceutical, 123 I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([ 123 I]ADAM), has been developed recently for evaluation of how serotonin transporters (SERT) function in the brain. However, the detailed biodistribution and specific binding in certain brain areas are not well investigated. In this study, both phosphor plate imaging and microautoradiography were applied to explore the binding characteristics of [ 123 I]ADAM in SERT neurons. The effect of two psychotropics and one narcotic on the binding of [ 123 I]ADAM to SERT was also studied. Fluoxetine and desipramine, both are psychotropics and specific SERT ligands and decreased the affinity of [ 123 I]ADAM, while p-chloroamphetamine (PCA), a narcotic, destroyed most of serotonergic neurons, as well as reducing the concentration of serotonin and the number of SERT in the brain as shown by the biodistribution of [ 123 I]ADAM. Significant and selective accumulation of [ 123 I]ADAM in the areas from midbrain to brain stem in normal mice with maximum target-to-background ratio was found at 90 minutes postinjection. A rapid clearance of [ 131 I]ADAM at 120 minutes postinjection was found in the CA1, CA3 and ThN brain areas. In addition, the inhibition effect on binding ability of [ 123 I]ADAM to SERT by the psychotropics and the narcotic was found to have the order of: PCA > fluoxetine > desipramine

  6. A Four-Step Block Hybrid Adams-Moulton Methods For The Solution ...

    African Journals Online (AJOL)

    This paper examines application of the Adam-Moulton's Method and proposes a modified self-starting continuous formula Called hybrid Adams-Moulton methods for the case k=4. It allows evaluation at both grid and off grid points to obtain the discrete schemes used in the block methods. The order, error constant and ...

  7. The shedding activity of ADAM17 is sequestered in lipid rafts

    International Nuclear Information System (INIS)

    Tellier, Edwige; Canault, Matthias; Rebsomen, Laure; Bonardo, Bernadette; Juhan-Vague, Irene; Nalbone, Gilles; Peiretti, Franck

    2006-01-01

    The tumor necrosis factor-alpha (TNF) converting enzyme (ADAM17) is a metalloprotease-disintegrin responsible for the cleavage of several biologically active transmembrane proteins. However, the substrate specificity of ADAM17 and the regulation of its shedding activity are still poorly understood. Here, we report that during its transport through the Golgi apparatus, ADAM17 is included in cholesterol-rich membrane microdomains (lipid rafts) where its prodomain is cleaved by furin. Consequently, ADAM17 shedding activity is sequestered in lipid rafts, which is confirmed by the fact that metalloproteinase inhibition increases the proportion of ADAM17 substrates (TNF and its receptors TNFR1 and TNFR2) in lipid rafts. Membrane cholesterol depletion increases the ADAM17-dependent shedding of these substrates demonstrating the importance of lipid rafts in the control of this process. Furthermore, ADAM17 substrates are present in different proportions in lipid rafts, suggesting that the entry of each of these substrates in these particular membrane microdomains is specifically regulated. Our data support the idea that one of the mechanisms regulating ADAM17 substrate cleavage involves protein partitioning in lipid rafts

  8. Retorika in Adam Small se "Kanna hy kô hystoe" | van Zyl | Tydskrif ...

    African Journals Online (AJOL)

    Adam Small, Kanna and 'that moral moment' This essay revisits Adam Small's best known play Kanna hy kô hystoe (“Kanna he comes home”, 1965) in order to evaluate its relevance for contemporary readers and audiences. The text, considered one of the classics of Afrikaans literature, is analysed from a rhetorical point of ...

  9. At læse Adam Smith er både befriende og irriterende

    DEFF Research Database (Denmark)

    Larsen, Steen Nepper

    2014-01-01

    Anmeldelse af Adam Smith: "Teorien om de moralske følelser", oversat af Claus Bratt Østergaard, udg. på Informations Forlag......Anmeldelse af Adam Smith: "Teorien om de moralske følelser", oversat af Claus Bratt Østergaard, udg. på Informations Forlag...

  10. ADAM: A computer program to simulate selective-breeding schemes for animals

    DEFF Research Database (Denmark)

    Pedersen, L D; Sørensen, A C; Henryon, M

    2009-01-01

    ADAM is a computer program that models selective breeding schemes for animals using stochastic simulation. The program simulates a population of animals and traces the genetic changes in the population under different selective breeding scenarios. It caters to different population structures......, genetic models, selection strategies, and mating designs. ADAM can be used to evaluate breeding schemes and generate genetic data to test statistical tools...

  11. A new species of Casmaria H. Adams & A. Adams, 1853 (Gastropoda, Cassidae from the Philippines identified by molecular data

    Directory of Open Access Journals (Sweden)

    Alexander Fedosov

    2014-03-01

    Full Text Available The genus Casmaria H. Adams & A. Adams, 1853 (family Cassidae is widespread in the tropical Indo-Pacific and has been documented from some Atlantic localities as well. Two Casmaria species, C. erinaceus (Linnaeus, 1758 and C. ponderosa (Gmelin, 1791, are common in Indo-Pacific shallow-water sandy bottom communities and are characterized by high morphological variability; both species encompass multiple, often sympatric forms of uncertain status. In the present study we carry out a phylogenetic analysis of some Philippine Casmaria morphs and demonstrate that one of the distinctive morphs earlier assigned to Casmaria ponderosa is in fact a different species, which we describe as Casmaria boblehmani sp. nov. The smooth form of Casmaria ponderosa, C. ponderosa ponderosa, and the solid nodulose form, widely called “form nodulosa” despite being strikingly different in shell morphology, are shown to be conspecific. Studied specimens of these two morphs even from different localities share the same haplotype of the CO1 gene. In light of these new data on the morphological variability of Casmaria species, we discuss criteria of species delimitation in the genus Casmaria and possible affinities of Casmaria boblehmani sp. nov. within the genus.

  12. ADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis

    International Nuclear Information System (INIS)

    Goeoz, Pal; Goeoz, Monika; Baldys, Aleksander; Hoffman, Stanley

    2009-01-01

    Modulation of angiogenesis is a promising approach for treating a wide variety of human diseases including ischemic heart disease and cancer. In this study, we show that ADAM-17 is an important regulator of several key steps during angiogenesis. Knocking down ADAM-17 expression using lentivirus-delivered siRNA in HUVECs inhibited cell proliferation and the ability of cells to form close contact in two-dimensional cultures. Similarly, ADAM-17 depletion inhibited the ability of HUVECs to form capillary-like networks on top of three-dimensional Matrigel as well as in co-culture with fibroblasts within a three-dimensional scaffold. In mechanistic studies, both baseline and VEGF-induced MMP-2 activation and Matrigel invasion were inhibited by ADAM-17 depletion. Based on our findings we propose that ADAM-17 is part of a novel pro-angiogenic pathway leading to MMP-2 activation and vessel formation.

  13. ADAM12: a novel first-trimester maternal serum marker for Down syndrome

    DEFF Research Database (Denmark)

    Laigaard, Jennie; Sørensen, Tina; Fröhlich, Camilla

    2003-01-01

    levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. METHODS: We......OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum...... developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration. RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g...

  14. John Tyndall's religion: a fragment

    Science.gov (United States)

    Cantor, Geoffrey

    2015-01-01

    Both contemporaries and historians have focused on the high-profile 1874 Belfast Address in which John Tyndall was widely perceived as promulgating atheism. Although some historians have instead interpreted him as a pantheist or an agnostic, it is clear that any such labels do not accurately capture Tyndall's religious position throughout his life. By contrast, this paper seeks to chart Tyndall's religious journey from 1840 (when he was in his late teens) to the autumn of 1848 when he commenced his scientific studies at Marburg. Although he had been imbued with his father's stern conservative Irish Protestantism and opposition to Catholicism, as a youth he seems for a time to have been attracted to Methodism. Later, however, he questioned and rejected his father's religious views and was increasingly drawn to the more spiritual outlook of Ralph Waldo Emerson and Thomas Carlyle, along with a more radical attitude to politics.

  15. ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

    Science.gov (United States)

    Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

    2014-08-01

    Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.

  16. New Processing of Spaceborne Imaging Radar-C (SIR-C) Data

    Science.gov (United States)

    Meyer, F. J.; Gracheva, V.; Arko, S. A.; Labelle-Hamer, A. L.

    2017-12-01

    The Spaceborne Imaging Radar-C (SIR-C) was a radar system, which successfully operated on two separate shuttle missions in April and October 1994. During these two missions, a total of 143 hours of radar data were recorded. SIR-C was the first multifrequency and polarimetric spaceborne radar system, operating in dual frequency (L- and C- band) and with quad-polarization. SIR-C had a variety of different operating modes, which are innovative even from today's point of view. Depending on the mode, it was possible to acquire data with different polarizations and carrier frequency combinations. Additionally, different swaths and bandwidths could be used during the data collection and it was possible to receive data with two antennas in the along-track direction.The United States Geological Survey (USGS) distributes the synthetic aperture radar (SAR) images as single-look complex (SLC) and multi-look complex (MLC) products. Unfortunately, since June 2005 the SIR-C processor has been inoperable and not repairable. All acquired SLC and MLC images were processed with a course resolution of 100 m with the goal of generating a quick look. These images are however not well suited for scientific analysis. Only a small percentage of the acquired data has been processed as full resolution SAR images and the unprocessed high resolution data cannot be processed any more at the moment.At the Alaska Satellite Facility (ASF) a new processor was developed to process binary SIR-C data to full resolution SAR images. ASF is planning to process the entire recoverable SIR-C archive to full resolution SLCs, MLCs and high resolution geocoded image products. ASF will make these products available to the science community through their existing data archiving and distribution system.The final paper will describe the new processor and analyze the challenges of reprocessing the SIR-C data.

  17. Econophysical visualization of Adam Smith’s invisible hand

    Science.gov (United States)

    Cohen, Morrel H.; Eliazar, Iddo I.

    2013-02-01

    Consider a complex system whose macrostate is statistically observable, but yet whose operating mechanism is an unknown black-box. In this paper we address the problem of inferring, from the system’s macrostate statistics, the system’s intrinsic force yielding the observed statistics. The inference is established via two diametrically opposite approaches which result in the very same intrinsic force: a top-down approach based on the notion of entropy, and a bottom-up approach based on the notion of Langevin dynamics. The general results established are applied to the problem of visualizing the intrinsic socioeconomic force-Adam Smith’s invisible hand-shaping the distribution of wealth in human societies. Our analysis yields quantitative econophysical representations of figurative socioeconomic forces, quantitative definitions of “poor” and “rich”, and a quantitative characterization of the “poor-get-poorer” and the “rich-get-richer” phenomena.

  18. Parameterized Analysis of 2-DOF Motion Platform Based on ADAMS

    Directory of Open Access Journals (Sweden)

    Hu Hanyuan

    2015-01-01

    Full Text Available According to the functions of parametric modeling and analysis from ADAMS, this thesis was established a parametric simulation model in order to optimize the rated output power of electric cylinders according to the real field environment. First, the variable which could affect sensitivity of the output variables was chosen by the electric cylinder’s elongation which was obtained through loop vector method. Then this thesis tried to get the optimum optimization design parameters through the simulation, and the change of rated output power affected by the change of parameters, meanwhile, made a filter and calibration of parameters which have greater influence on sensibilities. The goal of design could meet the qualification with less work load and faster speed. It is concluded that the change of the location parameters affects the rated output power.

  19. Lance-Adams syndrome associated with cerebellar pathology.

    Science.gov (United States)

    Waddell, Adam; Dirweesh, Ahmed; Ordonez, Fausto; Kososky, Charles; Reddy Peddareddygari, Leema; Grewal, Raji P

    2017-07-01

    Lance-Adams syndrome (LAS) is an uncommon neurological disorder characterized by the development of chronic post-hypoxic myoclonus. There are relatively few cases described following successful cardiopulmonary resuscitation. We report a patient who developed LAS 3 months after successful resuscitation. Cerebral imaging studies indicate that brain pathology in LAS patients is not uniform, suggesting that the pathophysiology of myoclonus may vary from patient to patient. Our patient adds to this etiological heterogeneity by demonstrating the unusual feature of cerebellar pathology by both cerebral magnetic resonance imaging and single-photon emission computed tomography scans. There is also heterogeneity of these patients in their response to therapy. Unlike some patients described in the literature, our patient has not responded to drug treatment. Studies of these rare patients with LAS are important as they provide insight into the pathophysiology of this condition which, it is hopefully, will facilitate the development of more effective therapy.

  20. Tuberculous spondylitis in Haji Adam Malik hospital, Medan

    Science.gov (United States)

    Dharmajaya, R.

    2018-03-01

    Ankylosing tuberculosis is an infection caused by Mycobacterium tuberculosis in one or more components of the vertebrae; it is Pott disease or tuberculous spondylitis. It might become a potential cause of morbidity, including neurological deficits and permanent deformity of the spine. Management of TB Spondylitis, in general, is chemotherapy with antituberculosis drugs (ATG), immobilization, and spine surgical interventions. A retrospective study was conducted to analyze the patients of TB Spondylitis who had undergone surgery at Haji Adam Malik hospital from June 2015 to June 2017. The most common location is thoracal (10%), lumbal (3%), and thoracolumbal junction (3%). Decompression laminectomy with fusion (18%) is the most suitable option for surgical management. The majority, pre- operation ASIA scale is D (8%), and post operation is E (8%). It means that surgical plays an important role in themanagement of tuberculous spondylitis.

  1. Adam Smith and the new era of China

    Directory of Open Access Journals (Sweden)

    Aníbal Carlos Zottele

    2013-01-01

    Full Text Available ural area has been the quiet main character of China’s economic development. The history of this thousand-year-old culture seems to be exempted from further comments about its role. Its importance has been strongly expressed during crisis which institutions of that great nation in XX century were shook. Agricultural sector was the key in modernization period initiated in 1980 even in the later phases. Agriculture preponderance as progress support of the nations is presented by Scottish thinker Adam Smith in his work An Inquiry into the Nature and Causes of the Wealth of Nations. The status of Chinese development in XVII y XVIII centuries has been characterized in this document as well as the natural order of progress against unnatural or retrograde order followed by the Netherlands, in that time the country that had achieved higher levels growth in Europe. Apparently, at present, China repeats its old experiences by concentrating on the path praised by Smith.

  2. Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

    Science.gov (United States)

    Gabrinetti, Paul A; Özler, Sule

    2014-10-01

    In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.

  3. Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

    Science.gov (United States)

    Sheehan, William

    2011-01-01

    As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

  4. Obituary: John Norris Bahcall, 1934-2005

    Science.gov (United States)

    Striker, Jeremiah P.; Bahcall, Neta A.

    2007-12-01

    statesman of unusual and beneficent influence. Bahcall moved to the Institute for Advanced Study (IAS) at Princeton in 1968 and soon established that institution as a magnet and model for postdoctoral training. A significant fraction of the world's most distinguished astrophysicists benefited from his tutelage and the intellectually fertile atmosphere that he established there. The eminent British scientist Sir Martin Rees describes himself as fortunate to have been one of the first IAS postdoctoral fellows in astrophysics in 1969. Every fellow's birthday and important family events were celebrated. The intellectual atmosphere was intense, and the weekly Tuesday lunches, with John presiding, to which the whole Princeton physics community was invited, were legendary (now named the Bahcall Lunches). Bahcall's postdoc program was the one that astrophysics institutions worldwide emulated. At the IAS, young scientists were selected and recruited in the most exacting manner and then were free to work on whatever they wanted, with whomever they wished. Bahcall mentored over 200 young astronomers in his four decades at the IAS. While maintaining a scientific and educational program that would have exhausted most, Bahcall also demonstrated extraordinary scientific leadership. He was president of the American Astronomical Society, president-elect of the American Physical Society, led the team that produced the 1990 National Research Council "Bahcall Report" that set the scientific and instrumental priorities for astrophysics in the United States for a decade, and worked (with Lyman Spitzer, Jr.) with tireless effectiveness in public and in private to have the Hubble Space Telescope and the Space Telescope Science Institute (STScI) built and maintained as one of the world's pre-eminent scientific facilities. Neta Bahcall, a professor of astrophysics at Princeton University, was his love, his best friend, and his scientific colleague throughout. She took a leading scientific role at

  5. Verification of the linearity of the new SIR using sources of 64Cu and 99mTc

    International Nuclear Information System (INIS)

    Michotte, Carine

    2012-02-01

    The linearity of the new SIR electronics has been verified by looking for deviations from the exponential decay for several 64 Cu and 99m Tc sources. Data analyses are compared with the half-life used as a fixed or free parameter. It is concluded that no significant non-linearity is observed in the new SIR. For comparison, the same method has been applied to analyse existing data from the original SIR. (author)

  6. Serum inflammatory markers in the elderly: are they useful in differentiating sepsis from SIRS?

    Directory of Open Access Journals (Sweden)

    Mahshid Talebi-Taher

    2014-06-01

    Full Text Available Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP, Erythrocyte Sedimentation Rate (ESR, procalcitonin (PCT, and Interleukin-6 (IL-6 to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98% and negative predictive value (98.6% and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI. On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

  7. Constitutive Relation of Engineering Material Based on SIR Model and HAM

    Directory of Open Access Journals (Sweden)

    Haoxiang He

    2014-01-01

    Full Text Available As an epidemic mathematical model, the SIR model represents the transition of the Susceptible, Infected, and Recovered. The profound implication of the SIR model is viewed as the propagation and dynamic evolutionary process of the different internal components and the characteristics in a complex system subject to external effect. The uniaxial stress-strain curve of engineering material represents the basic constitutive relation, which also represents the damage propagation in the units of the damaged member. Hence, a novel dynamic stress-strain model is established based on the SIR model. The analytical solution and the approximate solution for the proposed model are represented according to the homotopy analysis method (HAM, and the relationship of the solution and the size effect and the strain rate is discussed. In addition, an experiment on the size effect of confined concrete is carried out and the solution of SIR model is suitable for simulation. The results show that the mechanical mechanism of the parameters of the uniaxial stress-strain model proposed in this paper reflects the actual characteristics of the materials. The solution of the SIR model can fully and accurately show the change of the mechanical performance and the influence of the size effect and the strain rate.

  8. SIRS score on admission and initial concentration of IL-6 as severe acute pancreatitis outcome predictors.

    Science.gov (United States)

    Gregoric, Pavle; Pavle, Gregoric; Sijacki, Ana; Ana, Sijacki; Stankovic, Sanja; Sanja, Stankovic; Radenkovic, Dejan; Dejan, Radenkovic; Ivancevic, Nenad; Nenad, Ivancevic; Karamarkovic, Aleksandar; Aleksandar, Karamarkovic; Popovic, Nada; Nada, Popovic; Karadzic, Borivoje; Borivoje, Karadzic; Stijak, Lazar; Stefanovic, Branislav; Branislav, Stefanovic; Milosevic, Zoran; Zoran, Milosević; Bajec, Djordje; Djordje, Bajec

    2010-01-01

    Early recognition of severe form of acute pancreatitis is important because these patients need more agressive diagnostic and therapeutical approach an can develope systemic complications such as: sepsis, coagulopathy, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS), Multiple Organ Failure (MOF). To determine role of the combination of Systemic Inflammatory Response Syndrome (SIRS) score and serum Interleukin-6 (IL-6) level on admission as predictor of illness severity and outcome of Severe Acute Pancreatitis (SAP). We evaluated 234 patients with first onset of SAP appears in last twenty four hours. A total of 77 (33%) patients died. SIRS score and serum IL-6 concentration were measured in first hour after admission. In 105 patients with SIRS score 3 and higher, initial measured IL-6 levels were significantly higher than in the group of remaining 129 patients (72 +/- 67 pg/mL, vs 18 +/- 15 pg/mL). All nonsurvivals were in the first group, with SIRS score 3 and 4 and initial IL-6 concentration 113 +/- 27 pg/mL. The values of C-reactive Protein (CRP) measured after 48h, Acute Physiology and Chronic Health Evaluation (APACHE II) score on admission and Ranson score showed the similar correlation, but serum amylase level did not correlate significantly with Ranson score, IL-6 concentration and APACHE II score. The combination of SIRS score on admission and IL-6 serum concentration can be early, predictor of illness severity and outcome in SAP.

  9. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    International Nuclear Information System (INIS)

    Endsley, Mark A.; Somasunderam, Anoma D.; Li, Guangyu; Oezguen, Numan; Thiviyanathan, Varatharasa; Murray, James L.; Rubin, Donald H.; Hodge, Thomas W.

    2014-01-01

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4 + T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4 + T lymphocytes

  10. Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

    Energy Technology Data Exchange (ETDEWEB)

    Endsley, Mark A., E-mail: maendsle@utmb.edu [Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (United States); Somasunderam, Anoma D., E-mail: asomasun@utmb.edu [Department Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (United States); Li, Guangyu, E-mail: LIG001@mail.etsu.edu [Department of Internal Medicine, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614 (United States); Oezguen, Numan, E-mail: numan.oezguen@bcm.edu [Department of Pathology and Immunology, Microbiome Center, Texas Children' s Hospital, Houston, TX 77030 (United States); Thiviyanathan, Varatharasa, E-mail: Varatharasa.Thiviyanathan@uth.tmc.edu [Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030 (United States); Murray, James L., E-mail: jmurray100@yahoo.com [GeneTAG Technology, Inc., 3155 Northwoods Place, Norcross, GA 30071 (United States); Rubin, Donald H., E-mail: don.h.rubin@vanderbilt.edu [Research Medicine, VA Tennessee Valley Healthcare System, 1310 24th Ave. South, Nashville, TN 37212 (United States); Departments of Medicine, Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, 1161 21st Ave South, Nashville, TN 37232 (United States); Hodge, Thomas W., E-mail: twhodge3@gmail.com [Pre-clinical and Antiviral Research, Tamir Biotechnology, Inc., 12625 High Bluff Dr., Suite 113, San Diego, CA 92130 (United States); and others

    2014-04-15

    Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizes with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.

  11. Cut loose and run: The complex role of ADAM proteases during neural crest cell development.

    Science.gov (United States)

    Alfandari, Dominique; Taneyhill, Lisa A

    2018-02-24

    ADAM metalloproteases have been shown to play critical roles during development. In this review, we will describe functional evidence that implicates ADAM proteins during the genesis, migration and differentiation of neural crest cells. We will restrict our analysis to the transmembrane ADAMs as other reviews have addressed the role of extracellular metalloproteases (Christian et al. [2013] Critical Reviews in Biochemistry and Molecular Biology 48:544-560). This review will describe advances that have been obtained mainly through the use of two vertebrate model systems, the frog, and avian embryos. The role of the principal substrates of ADAMs, the cadherins, has been extensively described in other reviews, most recently in (Cousin [1997] Mechanisms of Development 148:79-88; Taneyhill and Schiffmacher [2017] Genesis, 55). The function of ADAMs in the migration of other cell types, including the immune system, wound healing and cancer has been described previously in (Dreymueller et al. [2017] Mediators of Inflammation 2017: 9621724). Our goal is to illustrate both the importance of ADAMs in controlling neural crest behavior and how neural crest cells have helped us understand the molecular interactions, substrates, and functions of ADAM proteins in vivo. © 2018 Wiley Periodicals, Inc.

  12. ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function.

    Science.gov (United States)

    Suh, Jaehong; Choi, Se Hoon; Romano, Donna M; Gannon, Moira A; Lesinski, Andrea N; Kim, Doo Yeon; Tanzi, Rudolph E

    2013-10-16

    The generation of Aβ, the main component of senile plaques in Alzheimer's disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. [Effects of ADAM28 on biological functions of human dental pulp stem cells].

    Science.gov (United States)

    Zhao, Zheng; Liu, Hong-chen; E, Ling-ling; Wang, Yi; Wang, Dong-sheng

    2010-06-01

    To investigate the effects of a disintegrin and metalloproteinase 28 (ADAM28) on proliferation, differentiation and apoptosis of human dental pulp stem cells (HDPSCs) and the possible mechanism. Firstly, HDPSCs were isolated and cultured in vitro and identified. ADAM28 eukaryotic expression plasmid was constructed via gene rebuilt technique and transfected into HDPSCs. Then MTT chromatometry, enzyme dynamics and flow cytometry (FCM) techniques were performed to detect the effects of ADAM28 on biological characteristics of HDPSCs. Immunocytochemical and image analysis techniques were used to determine the influence of ADAM28 on HDPSCs expressing dentin sialophosphoprotein (DSPP), bone sialoprotein (BSP) and osteopontin (OPN). Statistical significance was assessed by the Student-Newman-Keuls (SNK) test with SPSS 13.0 software package. ADAM28 eukaryotic plasmid was constructed and transfected into HDPSCs for 48 hours successfully. In ADAM28 eukaryotic plasmid group, proliferation activity and index of HDPSCs were lower than those of pcDNA3.1(+) group and untransfected group significantly.Alkaline phosphatase (ALP) secretion level and percentage of apoptotic cells went up remarkly. Significant difference was detected between eukaryotic plasmid group and other groups (P<0.05). The expression level of DSPP in HDPSCs elevated significantly (P<0.05). ADAM28 could inhibit HDPSCs proliferation, promote ALP secretion activity and DSPP expression in HDPSCs and induce HDPSCs apoptosis significantly.

  14. SirT1—A Sensor for Monitoring Self-Renewal and Aging Process in Retinal Stem Cells

    Directory of Open Access Journals (Sweden)

    Chi-Hsien Peng

    2010-06-01

    Full Text Available Retinal stem cells bear potency of proliferation, self-renewal, and differentiation into many retinal cells. Utilizing appropriate sensors one can effectively detect the self-renewal and aging process abilities. Silencing information regulator (SirT1, a member of the sirtuin family, is a NAD-dependent histone deacetylase and an essential mediator for longevity in normal cells by calorie restriction. We firstly investigate the SirT1 mRNA expression in retinal stem cells from rats and 19 human eyes of different ages. Results revealed that SirT1 expression was significantly decreased in in vivo aged eyes, associated with poor self-renewal abilities. Additionally, SirT1 mRNA levels were dose-dependently increased in resveratrol- treated retinal stem cells. The expression of SirT1 on oxidative stress-induced damage was significantly decreased, negatively correlated with the level of intracellular reactive oxygen species production. Treatment with resveratrol could effectively further reduce oxidative stress induced by H2O2 treatment in retinal stem cells. Importantly, the anti-oxidant effects of resveratrol in H2O2-treated retinal stem cells were significantly abolished by knockdown of SirT1 expression (sh-SirT1. SirT1 expression provides a feasible sensor in assessing self-renewal and aging process in retinal stem cells. Resveratrol can prevent reactive oxygen species-induced damages via increased retinal SirT1 expression.

  15. EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study.

    Science.gov (United States)

    Bilgin Doğru, Elif; Dizdar, Yavuz; Akşit, Ece; Ural, Feyyaz; Şanlı, Öner; Yasasever, Vildan

    2014-11-01

    Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.

  16. Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

    Science.gov (United States)

    Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

    2015-10-01

    Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

  17. Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment

    Science.gov (United States)

    Peron, Rafaela; Vatanabe, Izabela Pereira; Manzine, Patricia Regina; Camins, Antoni

    2018-01-01

    ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer’s disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review. PMID:29382156

  18. Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells

    International Nuclear Information System (INIS)

    Hou, Y.; Chu, M.; Du, F.F.; Lei, J.Y.; Chen, Y.; Zhu, R.Y.; Gong, X.H.; Ma, X.; Jin, J.

    2013-01-01

    Highlights: •rhddADAM15 inhibited the proliferation and migration of Bel-7402 cells. •rhddADAM15 inhibited growth and metastasis of Bel-7402 cells in zebrafish xenograft. •rhddADAM15 induced apoptosis in Bel-7402 cells and somatic cells of zebrafish. •Cell-cycle in Bel-7402 cells showed a partial G 2 /S arrest. •Activity of caspases 8, 9 and 3 was increased in rhddADAM15-treated Bel-7402 cells. -- Abstract: ADAM15 (A Disintegrin And Metalloproteinase 15), a transmembrane protein containing seven domains, interacts with some integrins via its disintegrin domain and overexpresses in many solid tumors. In this study, the effect of the recombinant human disintegrin domain (rhddADAM15) on the proliferation and migration of Bel-7402 cells was evaluated in vitro and in vivo in zebrafish xenografts. rhddADAM15 (4 μM) severely inhibited the proliferation and migration of Bel-7402 cells, inducing a partial G 2 /S arrest and morphological nucleus changes of apoptosis. Moreover, the activity of caspases 8, 9 and 3 in Bel-7402 cells was increased. In addition, the zebrafish was used as a model for apoptosis-induction and tumor-xenograft. rhddADAM15 (1 pM) inhibited the growth and metastasis of Bel-7402 cell xenografts in zebrafish and a lower concentration (0.1 pM) induced severe apoptosis in the somatic cells of zebrafish. In conclusion, our data identified rhddADAM15 as a potent inhibitor of tumor growth and metastasis, making it a promising tool for use in anticancer treatment

  19. Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Y. [Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd., Wuxi, Jiangsu 214122 (China); Chu, M. [Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Medicine, Jiangnan University, 1800 Lihu Rd., Wuxi, Jiangsu 214122 (China); Du, F.F.; Lei, J.Y.; Chen, Y.; Zhu, R.Y.; Gong, X.H.; Ma, X. [Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd., Wuxi, Jiangsu 214122 (China); Jin, J., E-mail: jinjian31@126.com [Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd., Wuxi, Jiangsu 214122 (China)

    2013-06-14

    Highlights: •rhddADAM15 inhibited the proliferation and migration of Bel-7402 cells. •rhddADAM15 inhibited growth and metastasis of Bel-7402 cells in zebrafish xenograft. •rhddADAM15 induced apoptosis in Bel-7402 cells and somatic cells of zebrafish. •Cell-cycle in Bel-7402 cells showed a partial G{sub 2}/S arrest. •Activity of caspases 8, 9 and 3 was increased in rhddADAM15-treated Bel-7402 cells. -- Abstract: ADAM15 (A Disintegrin And Metalloproteinase 15), a transmembrane protein containing seven domains, interacts with some integrins via its disintegrin domain and overexpresses in many solid tumors. In this study, the effect of the recombinant human disintegrin domain (rhddADAM15) on the proliferation and migration of Bel-7402 cells was evaluated in vitro and in vivo in zebrafish xenografts. rhddADAM15 (4 μM) severely inhibited the proliferation and migration of Bel-7402 cells, inducing a partial G{sub 2}/S arrest and morphological nucleus changes of apoptosis. Moreover, the activity of caspases 8, 9 and 3 in Bel-7402 cells was increased. In addition, the zebrafish was used as a model for apoptosis-induction and tumor-xenograft. rhddADAM15 (1 pM) inhibited the growth and metastasis of Bel-7402 cell xenografts in zebrafish and a lower concentration (0.1 pM) induced severe apoptosis in the somatic cells of zebrafish. In conclusion, our data identified rhddADAM15 as a potent inhibitor of tumor growth and metastasis, making it a promising tool for use in anticancer treatment.

  20. Selective inhibition of ADAM12 catalytic activity through engineering of tissue inhibitor of metalloproteinase 2 (TIMP-2)

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Jacobsen, Jonas; Lee, Meng-Huee

    2010-01-01

    activity may be of great value therapeutically and as an investigative tool to elucidate its mechanisms of action. We have previously reported the inhibitory profile of TIMPs (tissue inhibitor of metalloproteinases) against ADAM12, demonstrating in addition to TIMP-3, a unique ADAM-inhibitory activity...... activity of TIMPs against the transmembrane ADAM12-L (full-length ADAM12), verifying the distinctive inhibitory abilities of N-TIMP-2 and engineered N-TIMP-2 mutants in a cellular environment. Taken together, our findings support the idea that a distinctive ADAM12 inhibitor with future therapeutic...

  1. Another Distortion of Adam Smith: The Case of the "Invisible Hand"

    OpenAIRE

    Michael Meeropol

    2004-01-01

    This paper addresses a major omission in the way textbook writers and journalists utilize Adam Smith’s concept of the “invisible hand” to make Adam Smith an intellectual precursor of modern neo-liberal economic policy. Specifically, the paper addresses the use of the concept of the “invisible hand” by Adam Smith to address two major issues in the debate over neo-liberal policy: the international flow of capital and its role in the location of investment projects and the inequality in the dist...

  2. Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action.

    Science.gov (United States)

    von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Klein, Stefan; Hamm, Christian; Qin, Qianqian; Meyenburg, Martina; Füser, Sabine; Saftig, Paul; Hellmann, Nadja; Postina, Rolf; Husmann, Matthias

    2016-07-01

    Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not known how α-toxin triggers ADAM10's enzymatic activity, and whether ADAM10 is invariably required for all α-toxin action on cells. In the present study, we show that efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of α-toxin, leading to significant increases in intracellular [Ca(2+)]; the fall in cellular ATP levels, typically following membrane perforation, became observable at far lower concentrations. Surprisingly, ADAM10 was dispensable for α-toxin-dependent xenophagic targeting of S. aureus, whereas a role for α-toxin attack on the plasma membrane was confirmed. The catalytic site of ADAM10, furin cleavage site, cysteine switch and intracellular domain of ADAM10 were not required for α-toxin binding and subsequent cytotoxicity. In contrast, an essential role for the disintegrin domain and the prodomain emerged. Thus, co-expression of the prodomain with prodomain-deficient ADAM10 reconstituted binding of α-toxin and susceptibility of ADAM10-deficient cells. The results of the present study may help to inform structural analyses of α-toxin-ADAM10 interactions and to design novel strategies to counteract S. aureus α-toxin action. © 2016 The Author(s). published by Portland Press Limited on behalf

  3. Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and Indirect Reductive Activity.

    Science.gov (United States)

    Granato, Daniela C; E Costa, Rute A P; Kawahara, Rebeca; Yokoo, Sami; Aragão, Annelize Z; Domingues, Romênia R; Pauletti, Bianca A; Honorato, Rodrigo V; Fattori, Juliana; Figueira, Ana Carolina M; Oliveira, Paulo S L; Consonni, Silvio R; Fernandes, Denise; Laurindo, Francisco; Hansen, Hinrich P; Paes Leme, Adriana F

    2018-02-27

    A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17 cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is unknown, and it has become of paramount importance to assess the degree of influence that Trx-1 has on metalloproteinase ADAM17. Combining discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively regulates ADAM17 by direct and indirect effect. We performed cell-based assays with synthetic peptides and site-directed mutagenesis, and we demonstrated that the interaction interface of Trx-1 and ADAM17 is important for the negative regulation of ADAM17 activity. However, both Trx-1 K72A and catalytic site mutant Trx-1 C32/35S rescued ADAM17 activity, although the interaction with Trx-1 C32/35S was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx-1 C32/35S mutant showed diminished reductive capacity, explaining this indirect effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx-1 K72A mutant showed similar oxidant levels to Trx-1 C32/35S , even though its catalytic site was preserved. We further demonstrated that the general reactive oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity. We show for the first time that the mechanism of ADAM17 regulation, Trx-1 dependent, can be by direct interaction and indirect effect, bringing new insights into the cross-talk between isomerases and mammalian metalloproteinases. This unexpected Trx-1 K72A behavior was due to more dimer formation and, consequently, the reduction of its Trx-1 reductase activity, evaluated through dimer verification, by gel filtration and mass

  4. Effects of [123I]ADAM, a serotonin transporter radiopharmaceutical, on pregnant Sprague–Dawley rats

    International Nuclear Information System (INIS)

    Chang, K.W.; Lin, M.C.; Lee, S.Y.; Chen, H.Y.; Chen, C.C.; Fu, Y.K.

    2012-01-01

    Serotonin transport abnormalities are implicated in neuropsychiatric disorders. [ 123 I]ADAM ([ 123 I]-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) is a novel radiotracer that targets serotonin transporters. We assessed the toxicity of [ 123 I]ADAM (18.5 MBq) administered in early- and late-phases (8 and 14 day postfertilization, respectively) of pregnancy. The mortality, clinical status, and gross necropsy were measured in pregnant rats, and the fertility index was measured in rat offspring (weight, clinical observations). We found no dosing-related clinical signs. In conclusion, [ 123 I]ADAM was not toxic in an animal pregnancy model.

  5. Comparison Virtual Landing Gear Drop Test for Commuter Aircraft Utilize MSC ADAMS And Solidworks Motion Analysis

    Science.gov (United States)

    Hidayat, Dony; Istiyanto, Jos; Agus Sumarsono, Danardono

    2018-04-01

    Loads at main landing gear while touchdown impact is function of aircraft weight and ground reaction load factor. In regulation states ground reaction load factor at Vsink = 3.05 m/s is below 3. Contact/impact force from simulation using MSC ADAMS is 94680 N, while using Solidworks Motion Analysis is 97691 N. The difference between MSC ADAMS and Solidworks Motion Analysis is 3.08%. The ground reaction load factor in MSC ADAMS is 2.78 while in Solidworks Motion Analysis is 2.87.

  6. The business of writing home: Authorship and the transatlantic economies of John Galt's literary circle, 1807-1840

    OpenAIRE

    Scott, Jennifer Anne

    2013-01-01

    This dissertation examines nineteenth-century Scottish author John Galt’s dialogue with the political economics of his time. In particular, I argue that both in his practices as an author and through the subject matter of his North American texts, Galt critiques and adapts Adam Smith’s The Wealth of Nations (1776). Galt’s critique of Smith becomes evident when we examine the relationship between his engagement with political economy in his most important North American literary texts and his ...

  7. BOREAS RSS-15 SIR-C and Landsat TM Biomass and Landcover Maps of the NSA

    Science.gov (United States)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Ranson, K. Jon

    2000-01-01

    As part of BOREAS, the RSS-15 team conducted an investigation using SIR-C, X-SAR, and Landsat TM data for estimating total above-ground dry biomass for the SSA and NSA modeling grids and component biomass for the SSA. Relationships of backscatter to total biomass and total biomass to foliage, branch, and bole biomass were used to estimate biomass density across the landscape. The procedure involved image classification with SAR and Landsat TM data and development of simple mapping techniques using combinations of SAR channels. For the SSA, the SIR-C data used were acquired on 06-Oct-1994, and the Landsat TM data used were acquired on 02-Sep-1995. The maps of the NSA were developed from SIR-C data acquired on 13-Apr-1994. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  8. Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

    Science.gov (United States)

    Haydar, Samir; Spanier, Matthew; Weems, Patricia; Wood, Samantha; Strout, Tania

    2017-11-01

    The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Delineation of major geologic structures in Turkey using SIR-B data

    Science.gov (United States)

    Toksoz, M. N.; Pettengill, G. H.; Ford, P.; Gulen, L.

    1984-01-01

    Shuttle Imaging Radar-B (SIR-B) images of well mapped segments of major faults, such as the North Anatolian Fault (NAF) and East Anatolian Fault (EAF) will be studied to identify the prominent signatures that characterize the fault zones for those specific regions. The information will be used to delineate the unmapped fault zones in areas with similar geological and geomorphological properties. The data obtained from SIR-B images will be compared and correlated with the LANDSAT thematic mapper and seismicity alignments based on well constrained earthquake epicenters.

  10. Automation of TL brick dating by ADAM-1

    International Nuclear Information System (INIS)

    Cechak, T.; Gerndt, J.; Hirsl, P.; Jirousek, P.; Kubelik, M.; Musilek, L.; Kanaval, J.

    2000-01-01

    Thermoluminescence has become an established dating method for ceramics and more recently for bricks. Based on the experiences of the work carried out since the late 1970's at the Rathgen-Forschungslabor in Berlin on the dating of bricks from historic architecture, and after evaluating all commercially available and some individually built automated and semi-automated TL-readers, a specially adapted machine for the fine grain dating of bricks was constructed in an interdisciplinary research project, undertaken by a team recruited from three faculties of the Czech Technical University in Prague. The result is the automated TL-reader ADAM-1 (Automated Dating Apparatus for Monuments) for the dating of historic architecture. Both the specific adaptation of the technique and the necessary optimal automation have influenced the design of this TL-reader. The principle advantage of brick as opposed to ceramic TL-dating emerges from the possibility of being able to obtain both a large number of samples and an above average quantity of datable material from each sample. This, together with the specific physical and chemical conditions in a brick wall, allowed a rethinking of the traditional error calculation and thus lower error margins as those obtained when dating ceramic shards. The TL-reader must therefore be able to measure and evaluate automatically numerous samples. The annular sample holder of ADAM-1 has 60 sample positions, which allow the irradiation and evaluation of samples taken from two locations. The thirty samples from one sampling point are divided into subgroups, which are processed in various ways. Three samples serve for a rough estimate of the TL sensitivity of the brick material. Nine samples are used for the measurement of 'natural TL' of the material. A further nine samples are used for testing the sensitivity of the material to beta radiation. The last nine samples serve for the testing of the sensitivity to alpha radiation. To determine the

  11. Paradise Lost: Difference between Adam and Eve’s Lament on Leaving Paradise - A Contrastive Analysis

    Directory of Open Access Journals (Sweden)

    Sara Torres Servín

    2013-01-01

    Full Text Available The difference between Adam and Eve’s lament on leaving Paradise in Milton’s Paradise Lost is striking in its contrastive content and depth. This paper analyzes the difference that exists between the feelings and spiritual attitudes that Adam and Eve express on the occasion when they are informed by the angel Michael that they have to abandon the Garden of Eden. It is a comparison of their lament in order to understand the contrast of the two attitudes that Milton wove in the tapestry that Paradise Lost is. The paper also explores male and female roles in Paradise Lost and concludes that Adam and Eve are equal yet different, that difference being the cause of their contrastive ways of expressing their sorrow. Adam and Eve manifest two contrastive worldviews in opposition, one spiritual (heavenly, and the other material (earthly.

  12. The role of metalloproteinase ADAM17 in regulating ICOS ligand-mediated humoral immune responses

    DEFF Research Database (Denmark)

    Marczynska, Joanna; Ozga, Aleksandra; Wlodarczyk, Agnieszka

    2014-01-01

    results in spleen and lymph node enlargement, as well as increased levels of Ag-specific class-switched Ig production following immunization with OVA together with anti-CD40 mAbs and polyinosinic-polycytidylic acid. Moreover, we demonstrate that the costimulatory ligand ICOS ligand (ICOSL) is selectively...... downregulated on the surface of B cells in an ADAM17-specific manner, although it is not proteolitically processed by recombinant ADAM17 in vitro. Finally, we show that higher cell surface levels of ICOSL in ADAM17(ex/ex) mice may contribute to the development of excessive Ab responses. Therefore, our data...... suggest a functional link between ADAM17 and ICOSL in controlling adaptive immune responses....

  13. ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

    Science.gov (United States)

    Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

    2010-01-01

    SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

  14. Review of The use of bodies by Giorgio Agamben, translated by Adam Kotsko

    OpenAIRE

    Taylor, Rachael

    2017-01-01

    This article reviews Giorgio Agamben's ninth installment in his Homo Sacer series, The Use of Bodies by Giorgio Agamben, translated by Adam Kotsko. The review considers Agamben's political philosophy framing of the body with reference to existentialist philosophy.

  15. FlipADAM: a potential new SPECT imaging agent for the serotonin transporter

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Julie L.; Deutsch, Eric C. [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Oya, Shunichi [Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Kung, Hank F., E-mail: kunghf@gmail.co [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States)

    2010-07-15

    Introduction: Single photon emission computed tomography (SPECT) imaging of the serotonin transporter (SERT) in the brain is a useful tool for examining normal physiological functions and disease states involving the serotonergic system. The goal of this study was to develop an improved SPECT radiotracer with faster kinetics than the current leading SPECT tracer, [{sup 123}I]ADAM, for selective SERT imaging. Methods: The in vitro binding affinities of (2-(2'-((dimethylamino)methyl)-4'-iodophenylthio)benzenamine) (FlipADAM) (1c), were determined using Hampshire pig kidney cells stably overexpressing the serotonin, norepinephrine (NET) or dopamine transporter (DAT). Localization of [{sup 125}I]FlipADAM (1c) was evaluated through biodistribution and autoradiography in male Sprague Dawley rats, and the specificity of binding was assessed by injecting selective SERT or NET inhibitors prior to [{sup 125}I]FlipADAM (1c). Results: FlipADAM (1c) displayed a high binding affinity for SERT (K{sub i}=1.0 nM) and good selectivity over NET and DAT binding (43-fold and 257-fold, respectively). [{sup 125}I]FlipADAM (1c) successfully penetrated the blood brain barrier, as evidenced by the brain uptake at 2 min (1.75% dose/g). [{sup 125}I]FlipADAM(1c) also had a good target to non-target (hypothalamus/cerebellum) ratio of 3.35 at 60 min post-injection. In autoradiography studies, [{sup 125}I]FlipADAM (1c) showed selective localization in SERT-rich brain regions such as the thalamic nuclei, amygdala, dorsal raphe nuclei and other areas. Conclusion: [{sup 125}I]FlipADAM (1c) exhibited faster clearance from the brain and time to binding equilibrium when compared to [{sup 125}I]2-(2'-((dimethylamino)methyl)-phenylthio)-5-iodophenylamine [{sup 125}I]ADAM (1b) and a higher target to non-target ratio when compared to [{sup 125}I]5-iodo-2-(2'-((dimethylamino)methyl)-phenylthio)benzyl alcohol [{sup 125}I]IDAM (1a). Therefore, [{sup 123}I]FlipADAM (1c) may be an improved

  16. Dysregulation of the ADAM17/Notch signalling pathways in endometriosis: from oxidative stress to fibrosis.

    Science.gov (United States)

    González-Foruria, Iñaki; Santulli, Pietro; Chouzenoux, Sandrine; Carmona, Francisco; Chapron, Charles; Batteux, Frédéric

    2017-07-01

    Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis? Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a consequent increase in fibrosis in patients with endometriosis. It is nowadays accepted that oxidative stress plays an important role in the onset and progression of endometriosis. Oxidative stress is able to induce the synthesis of some members of the 'ADAM' family, such as ADAM17. ADAM17/Notch signalling is dysregulated in other profibrotic and inflammatory diseases. This was a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n = 202) during surgery for a benign gynaecological condition. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free control women were enrolled. Peritoneal fluid (PF) samples were obtained from all the study participants during surgery in order to detect advanced oxidation protein products (AOPPs) and metalloproteinase activity of ADAM17. Stromal cells from endometrial specimens (n = 8) were obtained from endometrium of control patients (Cs), and from eutopic (Es) and ectopic (Ps) endometrium of patients with deep infiltrating endometriosis (DIE) (n = 8). ADAM17, Notch and the fibrosis markers α-smooth muscle actin (α-SMA) and type-I collagen were assessed using immunoblotting in all the endometrial samples obtained. Additionally, fibrosis was assessed after using Notch cleavage inhibitors (DAPT and FLI-06). Notch and fibrosis were also evaluated after stimulation of stromal endometrial cells with ADAM17 purified protein, increasing concentrations of H2O2 and primary cell culture supernatants. Patients with DIE presented higher PF AOPP

  17. The seals of Adam Sędziwój Czarnkowski, the general starost of Grand Poland

    Directory of Open Access Journals (Sweden)

    Marcin Hlebionek

    2011-12-01

    Full Text Available Adam Sędziwój Czarnkowski descended from an old noble family with origins in Grand Poland that can be traced back to at least the first half of the fourteenth century. He belonged to the younger family line started by Sędziwój Czarnkowski, the castellan of Przemęt (his brother, Maciej, is considered to be the progenitor of the older line, a son of Sędziwój, the voivode of the Poznań, and a grandson of Jan, the castellan of Gniezno. Adam was a grandson of Sędziwój and a son of Wojciech Sędziwój Czarnkowski, the general starost of Grand Poland, and Jadwiga Sierpska from Gulczewo of the Prawdzic coat-of-arms, the daughter of the voivode of Rawa. As a reward for his contribution to the wars with Russia, he was appointed the starost of Pyzdry by King Stefan Batory in 1579. At the same time, he inherited the title of the commander of the Knights of Saint John in Poznań (komandor poznańskich joannitów from his father. During the reign of king Sigismunt III, he was a supporter of the king. It was during that time that his career proceeded quickly: in 1593 he became the general starost of Grand Poland, and in 1606 he was appointed the voivode of Łęczyca. Not all of Adam Sędziwój Czarnkowski's seals survived to this day, but those remaining allow the analysis of the sigillographic collection of one of the oligarchs of Grand Poland. This collection, however, is specific. It seems to be unusually numerous when compared to the seal collections that belonged to other, even the richest, noblemen. That is because Czarnkowski's collection included official seals necessary to carry out the duties of the general starost and other, lower posts, e.g. those related to governing a castle court and office (urząd grodzki, as well as personal seals, which can be divided into several sub-categories. The collection grew mostly because Czarnkowski held the office of the general starost of Grand Poland and this required using seven, out of nine, known

  18. WIT Diversity Talk with John Ellis

    CERN Multimedia

    CERN. Geneva; Ellis, Jonathan R.

    2017-01-01

    Sudeshna Datta Cockerill, CERN Ombudsperson, will interview John Ellis, a renown British theoretical physicist with a long career both at CERN and externally. John Ellis has also been awarded several prizes for his work in physics. Among many other outstanding roles and positions, he was Division Leader of the Theory Division at CERN from 1988-1994. John Ellis is currently Clerk Maxwell Professor of Theoretical Physics at King's College London.

  19. STUDI KOMPARATIF KONSEP KETUHANAN ISLAM DAN AGAMA ADAM PADA KOMUNITAS SAMIN

    Directory of Open Access Journals (Sweden)

    Mohammad Rosyid

    2012-12-01

    Full Text Available Abstract: One of the problems that disturb the harmony between religious communities is a lack of understanding of the majority (mainstream religion about the local religion, and vice versa. This article aims to develop such inter-religious understanding by comparing between Islam and the religion of Adam, a local religion of Samin community. The comparative study was made within the scope of the concept of God in both religions. This study found that the understanding between Islam the religion of Adam about the concept of God is essential in common. God called Allah (in Islam and Yai (in the religion of Adam are equally perceived as condescendent, an only single power, and the Almighty. Both communities also share Adam as the first man in the world. So, it is not proportional if the public ridicule Samin community with atheist stigma.Abstrak: Salah satu problem yang mengganggu keharmonisan antar komunitas beragama adalah kurangnya pemahaman pemeluk agama mayoritas (mainstream di suatu negara tentang agama lokal, dan demikian pula sebaliknya. Artikel ini bertujuan untuk membangun kesalingpahaman antar pemeluk agama itu dengan melakukan kaji banding antara agama Islam dengan agama Adam, sebuah agama lokal komunitas Samin. Kaji banding itu dilakukan dalam lingkup konsep ketuhanan dalam dua agama itu. Kajian ini menemukan bahwa pemahaman antara Islam dengan agama Adam tentang konsep Tuhan memiliki kesamaan secara esensial. Tuhan yang disebut dengan Allah (dalam Islam dan Yai (dalam agama Adam sama-sama dipersepsikan sebagai tempat berlindung, kekuatan tunggal, dan Zat Yang Maha segala-galanya. Kedua komunitas juga sama dalam memandang Adam sebagai manusia yang pertama di dunia. Dengan adanya pemahaman itu maka tidak proporsional lagi jika publik mengolok-olok komunitas Samin dengan stigma ateis.

  20. Ansel Adams's Eucalyptus Tree, Fort Ross: Nature, Photography, and the Search for California

    OpenAIRE

    Adam Arenson

    2005-01-01

    This article considers the image of California evoked in the unusual Ansel Adams photograph Eucalyptus Tree, Fort Ross, California (1969), a Polaroid Land image of the garrison fence and an aged eucalyptus tree. Considering the participation of Russian occupation, Australian cross-pollination, Carleton Watkins's early photographs of redwoods, automotive and tourist images in the creation of this distinctive California place, the article argues that to understand Ansel Adams's work, we must no...

  1. MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.

    Directory of Open Access Journals (Sweden)

    Victor Chatterjee

    Full Text Available A disintegrin and metalloproteinase15 (ADAM15 has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS. An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3' UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression.

  2. Adams-Oliver syndrome associated with cutis marmorata telangiectatica congenita and congenital cataract: a case report.

    Science.gov (United States)

    Fayol, Laurence; Garcia, Patricia; Denis, Danièle; Philip, Nicole; Simeoni, Umberto

    2006-04-01

    A female infant presented with Adams-Oliver syndrome (AOS), intrauterine growth retardation, severe cutis marmorata telangiectatica congenita, bilateral congenital cataract, and periventricular lesions. The here-reported association of bilateral congenital cataract with AOS is original. Adams-Oliver syndrome is a genetic defect that causes a vasculopathy and leads to a variety of phenotypes. This observation further supports the current understanding of the physiopathology of AOS.

  3. (Re- Reading Adam Smith in a Time of Crisis

    Directory of Open Access Journals (Sweden)

    Ян Дуткевич

    2012-03-01

    Full Text Available At a time of not only empirical crisis, but also a philosophical crisis of the underpinning ideologies of the liberal capitalist economic system, there is an increasing tendency to dogmatize the work of classical thinkers, using selective readings of their work as the basis for support or critique of the status quo. Few are as subject to selective reading as the so-called father of modern economics, Adam Smith. This paper seeks to reflect on Smith's thought on two central aspects of the modern crisis: the nature of the limited liability corporation (whose profit motive is increasingly being challenged on a number of grounds and the role of the individual in a market economy (amid accusations from across the political and philosophical spectrum about the increasing isolation, individualization, and neo-liberalization of the self. These subjects are not as different as they might seem as they both relate to Smith's conception of the nature role of the individual actor - homo oeconomicus - not only in a market in and of itself, but in a market that Smith saw as a social creation and a part of a human community.

  4. ADAM SMITH: LA MANO INVISIBLE O LA CONFIANZA

    Directory of Open Access Journals (Sweden)

    Gache, Fernando Luis

    2010-12-01

    Full Text Available En 1776 Adam Smith planteó que una mano invisible era quien movía a los mercados para obtener su eficiencia. No obstante en el presente trabajo vamos a plantear la hipótesis, que dicha mano invisible, es en realidad la confianza que cada persona siente en el momento de hacer un negocio. Que además es única, pues es distinta a la confianza de los demás y que se trata de una variable no lineal que fundamentalmente está ligada a las respectivas historias personales. Para ello vamos a tomar como base el trabajo de Leopoldo Abadía (2009, respecto de la crisis económico financiera que se desató en el 2007-2008, para poner en evidencia la forma en que opera la confianza. Por lo tanto la contribución que esperamos hacer con este trabajo es destacar que, el nivel de confianza de los diferentes actores, es quien realmente mueve a los mercados, (por tanto la economía y que la crisis de las hipotecas subprime es una crisis de confianza a nivel mundial.

  5. Adam Smith om forholdet mellem moralske fornemmelser og naturen

    DEFF Research Database (Denmark)

    Huggler, Lise Oxenbøll

    2008-01-01

    I The Theory of Moral Sentiments giver Adam Smith en fremstilling af, hvordan mennesket i sam­fundslivet udvikler moralske fornemmelser og af den betydning, disse har for menneskers følelses- og handlingsliv. Her er synssansen afgørende, idet den sætter mennesket i stand til rumligt lokaliser......­bart at betragte andre menneskers opførsel såvel som andre menneskers reaktioner på ens egen opførsel. Den sætter derved på en entydig måde mennesket i stand til at forholde sig til sig selv og til andre mennesker. På dette grundlag opstiller Smith en række psykologiske reaktionsmønstre. Ikke desto mindre påkalder...... han jævnligt bl.a. naturen som en metafysisk entitet. Der skal her argumenteres for, at de metafysiske begreber har til opgave at skabe den sammenhæng i menneskelivet, som kausale reaktioner i sig selv ikke giver. I forlængelse af dette peges der på, at Smith synes at hævde, at mennesket i samfundet...

  6. The symbolism of Adam Asnyk with Muse by Jacek Malczewski

    Directory of Open Access Journals (Sweden)

    Haake, Michał

    2012-04-01

    Full Text Available The essay's goal is to interpret Jacek Malczewski's picture Adam Asnyk with Muse (1894-1897 as a symbolic work. The main argument is that the painting does not depict a scene with a poet being inspired by a muse. The starting point of the analysis is the conclusion that the Muse is not playing the lyre she is holding and that the wings of Hermes are attached only to one leg. The role of the instrument is crucial for the interpretation of the painting not only because it is not used in accordance with its function but also because of the planimetric as well as semantic relationships with other elements of the picture, above all with one of the sheets of paper on the table and the scythe held by a warrior in the spectral pageant. The Muse presses the sheet with the lyre, lifting it and directing its sharp point towards Asnyk's head. The sheet is made similar in its form to the scythe above it, directed towards the manacled young men above the poet. The comparison between the figures introduced in this way suggests that the real nature of the inspiration is destructive for the poet. A comprehensive interpretation of the relationship thus constituted leads to the conclusion that the symbolic meaning of the painting is based on the opposition between the conventional iconography of a poet and the idea of creation conceived as a liberation of the artist from traditional and ossified symbolism (music, the wings of Hermes.

  7. IL-1beta signals through the EGF receptor and activates Egr-1 through MMP-ADAM.

    Directory of Open Access Journals (Sweden)

    Estella Sanchez-Guerrero

    Full Text Available The immediate-early gene Egr-1 controls the inducible expression of many genes implicated in the pathogenesis of a range of vascular disorders, yet our understanding of the mechanisms controlling the rapid expression of this prototypic zinc finger transcription factor is poor. Here we show that Egr-1 expression induced by IL-1beta is dependent on metalloproteinases (MMP and a disintegrin and a metalloproteinase (ADAM. Pharmacologic MMP/ADAM inhibitors and siRNA knockdown prevent IL-1beta induction of Egr-1. Further, IL-1beta activates Egr-1 via the epidermal growth factor receptor (EGFR. This is blocked by EGFR tyrosine kinase inhibition and EGFR knockdown. IL-1beta induction of Egr-1 expression is reduced in murine embryonic fibroblasts (mEFs deficient in ADAM17 despite unbiased expression of EGFR and IL-1RI in ADAM17-deficient and wild-type mEFs. Finally, we show that IL-1beta-inducible wound repair after mechanical injury requires both EGFR and MMP/ADAM. This study reports for the first time that Egr-1 induction by IL-1beta involves EGFR and MMP/ADAM-dependent EGFR phosphorylation.

  8. ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview

    Directory of Open Access Journals (Sweden)

    Soichi Takeda

    2016-05-01

    Full Text Available A disintegrin and metalloproteinase (ADAM family proteins constitute a major class of membrane-anchored multidomain proteinases that are responsible for the shedding of cell-surface protein ectodomains, including the latent forms of growth factors, cytokines, receptors and other molecules. Snake venom metalloproteinases (SVMPs are major components in most viper venoms. SVMPs are primarily responsible for hemorrhagic activity and may also interfere with the hemostatic system in envenomed animals. SVMPs are phylogenetically most closely related to ADAMs and, together with ADAMs and related ADAM with thrombospondin motifs (ADAMTS family proteinases, constitute adamalysins/reprolysins or the M12B clan (MEROPS database of metalloproteinases. Although the catalytic domain structure is topologically similar to that of other metalloproteinases such as matrix metalloproteinases, the M12B proteinases have a modular structure with multiple non-catalytic ancillary domains that are not found in other proteinases. Notably, crystallographic studies revealed that, in addition to the conserved metalloproteinase domain, M12B members share a hallmark cysteine-rich domain designated as the “ADAM_CR” domain. Despite their name, ADAMTSs lack disintegrin-like structures and instead comprise two ADAM_CR domains. This review highlights the current state of our knowledge on the three-dimensional structures of M12B proteinases, focusing on their unique domains that may collaboratively participate in directing these proteinases to specific substrates.

  9. ADAMS/WT advanced development - version 1.4 and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Elliott, A.S.; Depauw, T.R. [Mechanical Dynamics, Inc., Mesa, AZ (United States)

    1996-12-31

    ADAMS/WT is an wind-turbine-specific shell for the general-purpose mechanical system simulation package ADAMS5. It was developed under the guidance of the National Renewable Energy Laboratory to give engineers and analysts in the wind turbine community access to the analytical power of ADAMS, without having to become expert in its particular technology. The 1.4 version of ADAMS/WT is the most recent upgrade to the package, incorporating the most up-to-date version of the AeroDyn aerodynamic forcing subroutines from the University of Utah. It is also the first version to be made available on the Windows/NT platform. In version 1.4, ADAMS/WT has been significantly improved throughout and runs much faster. Automatic generation of standardized output has been added. The documentation has been extensively augmented with more detailed descriptions, more figures and more examples. ADAMS/WT remains the most powerful analytical tool available for horizontal-axis wind turbine development. 10 figs.

  10. In silico investigation of ADAM12 effect on TGF-β receptors trafficking

    Directory of Open Access Journals (Sweden)

    LeMeur Nolwenn

    2009-09-01

    Full Text Available Abstract Background The transforming growth factor beta is known to have pleiotropic effects, including differentiation, proliferation and apoptosis. However the underlying mechanisms remain poorly understood. The regulation and effect of TGF-β signaling is complex and highly depends on specific protein context. In liver, we have recently showed that the disintegrin and metalloproteinase ADAM12 interacts with TGF-β receptors and modulates their trafficking among membranes, a crucial point in TGF-β signaling and development of fibrosis. The present study aims to better understand how ADAM12 impacts on TGF-β receptors trafficking and TGF-β signaling. Findings We extracted qualitative biological observations from experimental data and defined a family of models producing a behavior compatible with the presence of ADAM12. We computationally explored the properties of this family of models which allowed us to make novel predictions. We predict that ADAM12 increases TGF-β receptors internalization rate between the cell surface and the endosomal membrane. It also appears that ADAM12 modifies TGF-β signaling shape favoring a permanent response by removing the transient component observed under physiological conditions. Conclusion In this work, confronting differential models with qualitative biological observations, we obtained predictions giving new insights into the role of ADAM12 in TGF-β signaling and hepatic fibrosis process.

  11. An Adamic incarnational Christological framework as a theological approach for African contextual ministry

    Directory of Open Access Journals (Sweden)

    Magezi, Vhumani

    2016-12-01

    Full Text Available Many African Christian thinkers and writers are responding to the foreignness of Christ in African Christianity by treating Christ under the traditional African ancestral category. However, it is our contention that the designation of the ancestral category to Christ has a tendency of diminishing the actuality of Christ as God incarnate and encouraging syncretism in African Christianity. Given this, this paper proposes and formulates an Adamic incarnational Christological model as an alternative response to the foreignness of Christ in African Christianity. In employing the anhypostastic and enhypostastic principles, we demonstrate that Jesus Christ is not a foreigner to African Christians, since the human nature he assumed in the incarnation is a general human nature which embraces all humankind. In establishing the Adam-Christ relationship in Romans 5:12-21 and 1 Corinthians 15:21-22, we advance Adam as a biblical-theological category in enhancing the relevance of Christ to Africans. It is from this perspective that our Adamic incarnational Christological model proposes that in the incarnation, God in Christ fully identified with all mankind as the New Adam, acting from the ontological depth of his divine-human existence to save African Christians from sin and all its consequences, including death and opposing spiritual forces. Thus, our own model underscores the relevance of Christ to African Christians by emphasizing Christs complete solidarity with all humanity as the New Adam.

  12. 'The chearful haunts': John Armstrong (1709-1779), physician, poet, satirist and leveller of medical knowledge.

    Science.gov (United States)

    Bryan, Charles S; Scott, Patrick

    2015-11-01

    John Armstrong, the first honours graduate of the University of Edinburgh School of Medicine, was famous in his day for a lengthy didactic poem entitled The Art of Preserving Health (1744). He is now obscure except to scholars specializing in the 18th century and, when discussed at all, often dismissed as a failed physician who wrote mediocre poetry in a quest for money and fame. A new exegesis by Adam Budd exhumes Armstrong as an original voice who offered timely and reassuring advice to Britons as they braced for another epidemic of plague; who depicted illness through the lens of a vulnerable and sympathetic physician, and who was perhaps above all else a leveller of medical knowledge. Elaborating on Budd's thesis, it would seem that Armstrong, a complicated man, has frequently been misread and was in some ways ahead of his time. © The Author(s) 2014.

  13. Threshold Dynamics of a Stochastic SIR Model with Vertical Transmission and Vaccination

    OpenAIRE

    Miao, Anqi; Zhang, Jian; Zhang, Tongqian; Pradeep, B. G. Sampath Aruna

    2017-01-01

    A stochastic SIR model with vertical transmission and vaccination is proposed and investigated in this paper. The threshold dynamics are explored when the noise is small. The conditions for the extinction or persistence of infectious diseases are deduced. Our results show that large noise can lead to the extinction of infectious diseases which is conducive to epidemic diseases control.

  14. The Threshold of a Stochastic SIRS Model with Vertical Transmission and Saturated Incidence

    Directory of Open Access Journals (Sweden)

    Chunjuan Zhu

    2017-01-01

    Full Text Available The threshold of a stochastic SIRS model with vertical transmission and saturated incidence is investigated. If the noise is small, it is shown that the threshold of the stochastic system determines the extinction and persistence of the epidemic. In addition, we find that if the noise is large, the epidemic still prevails. Finally, numerical simulations are given to illustrate the results.

  15. Threshold Dynamics of a Stochastic SIR Model with Vertical Transmission and Vaccination

    Directory of Open Access Journals (Sweden)

    Anqi Miao

    2017-01-01

    Full Text Available A stochastic SIR model with vertical transmission and vaccination is proposed and investigated in this paper. The threshold dynamics are explored when the noise is small. The conditions for the extinction or persistence of infectious diseases are deduced. Our results show that large noise can lead to the extinction of infectious diseases which is conducive to epidemic diseases control.

  16. Lyapunov functions and global stability for SIR and SEIR models with age-dependent susceptibility

    KAUST Repository

    Korobeinikov, Andrei; Melnik, Andrey V.

    2013-01-01

    We consider global asymptotic properties for the SIR and SEIR age structured models for infectious diseases where the susceptibility depends on the age. Using the direct Lyapunov method with Volterra type Lyapunov functions, we establish conditions for the global stability of a unique endemic steady state and the infection-free steady state.

  17. A Possible Source For Sir Thomas More’s ‘Mountainish Inhumanity’

    NARCIS (Netherlands)

    Steenbergh, Kristine

    2017-01-01

    Shakespeare’s authorship of a scene in Sir Thomas More has been established as highly probable on the basis of an analysis of the handwriting, vocabulary, and collocations stylistics. His addition to the play was long believed to have been written soon after publication of the original play, in

  18. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation

    DEFF Research Database (Denmark)

    Lombard, David B; Alt, Frederick W; Cheng, Hwei-Ling

    2007-01-01

    Homologs of the Saccharomyces cerevisiae Sir2 protein, sirtuins, promote longevity in many organisms. Studies of the sirtuin SIRT3 have so far been limited to cell culture systems. Here, we investigate the localization and function of SIRT3 in vivo. We show that endogenous mouse SIRT3 is a solubl...

  19. Application of Homotopy Perturbation and Variational Iteration Methods to SIR Epidemic Model

    DEFF Research Database (Denmark)

    Ghotbi, Abdoul R.; Barari, Amin; Omidvar, M.

    2011-01-01

    effective strategy against childhood diseases, the development of the framework that would predict the optimal vaccine coverage level needed to prevent the spread of diseases is crucial. The SIR model is a standard compartmental model that has been used to describe many epidemiological diseases...

  20. 90Sr content in 90Y-labeled SIR-spheres and Zevalin.

    Science.gov (United States)

    Metyko, John; Erwin, William; Poston, John; Jimenez, Sandra

    2014-11-01

    Three different 90Y internally administered radionuclide therapies are currently used in both standard-of-care and clinical trial procedures atMD Anderson Cancer Center. TheraSphere and SIR-Spheres therapies utilize 90Y-labeled microspheres, while Zevalin is an 90Y-labeled radioimmunotherapeutic agent. Several publications have indicated radionuclidic impurities resulting from 90Y production methods. The 90Y in SIR-Spheres and Zevalin are produced from a 90Sr/90Y generator, which leaves measurable quantities of 90Sr in the final product. TheraSphere 90Y is produced in a nuclear reactor which results in a large number of impurities, most notably 88Y and 91Y. Product information sheets reference these impurities with specific limits given. These limits represent a tiny fraction of the total product activity, and in the case of TheraSphere and SIR-Spheres gamma-emitting impurities, this has been verified in the literature. An analysis of 90Sr impurities in SIR-Spheres and Zevalin is presented in this paper. Impurity quantities were found to be within the vendors’ documented limits.

  1. ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

    Science.gov (United States)

    Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

    2018-05-18

    A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

  2. C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress.

    Science.gov (United States)

    Chiang, Wei-Chung; Tishkoff, Daniel X; Yang, Bo; Wilson-Grady, Joshua; Yu, Xiaokun; Mazer, Travis; Eckersdorff, Mark; Gygi, Steven P; Lombard, David B; Hsu, Ao-Lin

    2012-09-01

    FoxO transcription factors and sirtuin family deacetylases regulate diverse biological processes, including stress responses and longevity. Here we show that the Caenorhabditis elegans sirtuin SIR-2.4--homolog of mammalian SIRT6 and SIRT7 proteins--promotes DAF-16-dependent transcription and stress-induced DAF-16 nuclear localization. SIR-2.4 is required for resistance to multiple stressors: heat shock, oxidative insult, and proteotoxicity. By contrast, SIR-2.4 is largely dispensable for DAF-16 nuclear localization and function in response to reduced insulin/IGF-1-like signaling. Although acetylation is known to regulate localization and activity of mammalian FoxO proteins, this modification has not been previously described on DAF-16. We find that DAF-16 is hyperacetylated in sir-2.4 mutants. Conversely, DAF-16 is acetylated by the acetyltransferase CBP-1, and DAF-16 is hypoacetylated and constitutively nuclear in response to cbp-1 inhibition. Surprisingly, a SIR-2.4 catalytic mutant efficiently rescues the DAF-16 localization defect in sir-2.4 null animals. Acetylation of DAF-16 by CBP-1 in vitro is inhibited by either wild-type or mutant SIR-2.4, suggesting that SIR-2.4 regulates DAF-16 acetylation indirectly, by preventing CBP-1-mediated acetylation under stress conditions. Taken together, our results identify SIR-2.4 as a critical regulator of DAF-16 specifically in the context of stress responses. Furthermore, they reveal a novel role for acetylation, modulated by the antagonistic activities of CBP-1 and SIR-2.4, in modulating DAF-16 localization and function.

  3. John Smithi kaks palet / Johannes Saar

    Index Scriptorium Estoniae

    Saar, Johannes, 1965-

    2003-01-01

    Näitus "John Smith. Marko ja Kaido" Tallinna Kunstihoones. Kaido Ole ja Marko Mäetamm esindavad rühmitusena "John Smith" Eestit 2003. a. Veneetsia biennaalil. Ilmunud ka kogumikus "Päevast päeva", lk. 90-96

  4. John of Salisbury on Aristotelian Science

    DEFF Research Database (Denmark)

    Bloch, David

    The First substantial treatment of John of Salisbury's views on Aristotelian science. Important for our understanding of the reception of Aristotle's works and for the history of theories of science.......The First substantial treatment of John of Salisbury's views on Aristotelian science. Important for our understanding of the reception of Aristotle's works and for the history of theories of science....

  5. John Kotter on Leadership, Management and Change.

    Science.gov (United States)

    Bencivenga, Jim

    2002-01-01

    Excerpts from interview with John Kotter, Konosuke Matsushita Professor of Leadership at the Harvard Business School, about his thoughts on the role of the superintendent as leader and manager. Describes his recent book "John P. Kotter on What Leaders Really Do," 1999. Lists eight-step change process from his book "Leading Change," 1996. (PKP)

  6. SIRS Digues 2.0: A Cooperative Software For Levees Management

    Directory of Open Access Journals (Sweden)

    Moins Isabelle

    2016-01-01

    Full Text Available SIRS Digues is a computing tool that makes informations on levees more durable and accessible in order to enhance their management. The first version of the software, which was IRSTEA’s initiative, was deployed in 2004. The second version was released in 2015. This article aims at pointing out the innovative aspects of this last version. They concern thematic and functionalities, computing technics and architecture, and last but not least, the business model chosen in order to build a long lasting software. The software’s kernel is sketched to propose a general description of levees: it focuses on description of the levees and linked objects, on disorders that affects them, on works... Most of these topics were already broached by the first version. The kernel of the version 2 may be extended using optional thematic modules. These modules concern: vegetation monitoring, reporting (in coherence with current French regulatory requirements, riverbanks, riverbed... Main functionnalities perfomed by SIRS Digues V1 and V2 are : data structuring and centralisation, quick access to relevant data, reporting and mapping, etc. SIRS Digues 2.0 updates and improves already existing functionalities of the first version. SIRS Digues V2 relies on an documentoriented NoSQL database, CouchDB, and on geospatial libraries, Geotoolkit and Apache-SIS. SIRS Digues V2 was released with a copyleft license. Copyrights belong to the French levees managers’ society, “France Digues”, which acts as a cooperative. Members put their heads together in order to gather their financial capacities and fund software development. France Digues has got the technical and thematic expertise and supply various services to the members. This business model aims to ensure accessibility, durability and adaptability of the software.

  7. ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis and increased tumor growth

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Kveiborg, Marie; Hansen, Dorte Stautz

    2013-01-01

    that there is a positive correlation between MMP-14 and ADAM12 expression in human breast cancer. We demonstrated that in 293-VnR and human breast cancer cells expressing ADAM12 at the cell surface, endogenous MMP-14 was recruited to the cell surface, resulting in its activation. Subsequent to this activation, gelatin......Matrix metalloproteinases (MMPs), in particular MMP-2, MMP-9 and MMP-14, play a key role in various aspects of cancer pathology. Likewise, ADAMs (a disintegrin and metalloproteinases), including ADAM12, are upregulated in malignant tumors and contribute to the pathology of cancers. Here, we show....... Furthermore, orthotopic implantation of ADAM12-expressing MCF7 cells in nude mice produced tumors with increased levels of activated MMP-14 and confirmed that ADAM12 protects tumor cells against apoptosis, leading to increased tumor progression. In conclusion, our data suggest that a ternary protein complex...

  8. 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM): an improved serotonin transporter ligand

    Energy Technology Data Exchange (ETDEWEB)

    Oya, Shunichi; Choi, S.-R.; Hou, Catherine; Mu Mu; Kung, M.-P.; Acton, Paul D.; Siciliano, Michael; Kung, Hank F. E-mail: kunghf@sunmac.spect.upenn.edu

    2000-04-01

    Serotonin transporters (SERT) are target-sites for commonly used antidepressants, such as fluoxetine, paroxetine, sertraline, and so on. Imaging of these sites in the living human brain may provide an important tool to evaluate the mechanisms of action as well as to monitor the treatment of depressed patients. Synthesis and characterization of an improved SERT imaging agent, ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine)(7) was achieved. The new compound, ADAM(7), displayed an extremely potent binding affinity toward SERT (K{sub i}=0.013 nM, in membrane preparations of LLC-PK{sub 1}-cloned cell lines expressing the specific monoamine transporter). ADAM(7) also showed more than 1,000-fold selectivity for SERT over norepinephrine transporter (NET) and dopamine transporter (DAT) (K{sub i}=699 and 840 nM, for NET and DAT, respectively). The radiolabeled compound [{sup 125}I]ADAM(7) showed an excellent brain uptake in rats (1.41% dose at 2 min post intravenous [IV] injection), and consistently displayed the highest uptake (between 60-240 min post IV injection) in hypothalamus, a region with the highest density of SERT. The specific uptake of [{sup 125}I]ADAM(7) in the hypothalamus exhibited the highest target-to-nontarget ratio ([hypothalamus - cerebellum]/cerebellum was 3.97 at 120 min post IV injection). The preliminary imaging study of [{sup 123}I]ADAM in the brain of a baboon by single photon emission computed tomography (SPECT) at 180-240 min post IV injection indicated a specific uptake in midbrain region rich in SERT. These data suggest that the new ligand [{sup 123}I]ADAM(7) may be useful for SPECT imaging of SERT binding sites in the human brain.

  9. 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (ADAM): an improved serotonin transporter ligand

    International Nuclear Information System (INIS)

    Oya, Shunichi; Choi, S.-R.; Hou, Catherine; Mu Mu; Kung, M.-P.; Acton, Paul D.; Siciliano, Michael; Kung, Hank F.

    2000-01-01

    Serotonin transporters (SERT) are target-sites for commonly used antidepressants, such as fluoxetine, paroxetine, sertraline, and so on. Imaging of these sites in the living human brain may provide an important tool to evaluate the mechanisms of action as well as to monitor the treatment of depressed patients. Synthesis and characterization of an improved SERT imaging agent, ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine)(7) was achieved. The new compound, ADAM(7), displayed an extremely potent binding affinity toward SERT (K i =0.013 nM, in membrane preparations of LLC-PK 1 -cloned cell lines expressing the specific monoamine transporter). ADAM(7) also showed more than 1,000-fold selectivity for SERT over norepinephrine transporter (NET) and dopamine transporter (DAT) (K i =699 and 840 nM, for NET and DAT, respectively). The radiolabeled compound [ 125 I]ADAM(7) showed an excellent brain uptake in rats (1.41% dose at 2 min post intravenous [IV] injection), and consistently displayed the highest uptake (between 60-240 min post IV injection) in hypothalamus, a region with the highest density of SERT. The specific uptake of [ 125 I]ADAM(7) in the hypothalamus exhibited the highest target-to-nontarget ratio ([hypothalamus - cerebellum]/cerebellum was 3.97 at 120 min post IV injection). The preliminary imaging study of [ 123 I]ADAM in the brain of a baboon by single photon emission computed tomography (SPECT) at 180-240 min post IV injection indicated a specific uptake in midbrain region rich in SERT. These data suggest that the new ligand [ 123 I]ADAM(7) may be useful for SPECT imaging of SERT binding sites in the human brain

  10. Analysis of membrane proteome and secretome in cells over-expressing ADAM17 using quantitative proteomics

    International Nuclear Information System (INIS)

    Kawahara, R.; Simabuco, F.M.; Yokoo, S.; Paes Leme, A.F.; Sherman, N.

    2012-01-01

    Full text: A disintegrin and metalloproteinase (ADAM) protease is involved in proteolytic ectodomain shedding of several membrane-associated proteins and modulation of key cell signaling pathways in the tumor microenvironment. In this study, we examined the effect of over-expressing the full length human ADAM17 in membrane and secreted proteins. To this end, we constructed a stable Flp-In T-RExHEK293 cells expressing ADAM17 by tetracycline induction. These cells were grown in Dulbeccos modified Eagles medium containing light lysine, arginine or heavy, L-Arg-13C615N4 and L-Lys -13C615N2 (SILAC: stable isotope labeling with amino acid in cell culture) media and they were treated with an ADAM17 activator, phorbolester (PMA). Controls such as Flp-In T-RExHEK293 cell without PMA treatment and without ADAM17 cloned were cultivated in light medium. The ADAM17 overexpression was induced with tetracycline 500 ng/ml for 24 hours. Cells in a heavy condition were treated with PMA 50 ng/ml for 1 hour and vehicle DMSO was used as control in a light cell condition. The extracellular media were collected, concentrated and used to evaluate the secretome and a cell surface biotinylation-based approach was used to capture cell surface-associated proteins. The biotinylated proteins were eluted with dithiothreitol, alkylated with iodoacetamide and then digested with trypsin. The resulting peptides were subjected to LC-MS/MS analysis on an ETD enabled Orbitrap Velos instrument. The results showed different proteins up or down regulated in membrane and secretome analysis which might represent potential molecules involved in signaling or ADAM17 regulation events. (author)

  11. SirT1 confers hypoxia-induced radioresistance via the modulation of c-Myc stabilization on hepatoma cells

    International Nuclear Information System (INIS)

    Xie Yuexia; Zhang Jianghong; Shao Chunlin; Xu Yanwu

    2012-01-01

    Intratumoral hypoxia is an important contributory factor to tumor cell resistance to radiotherapy. SirT1, a nicotinamide adenine dinucleotide (NAD + )-dependent histone/protein deacetylase, has been linked to the decrease of radiation-induced DNA damage and seems to be critical for cancer therapy. The purpose of this study was to investigate the role of SirT1 in hypoxia-induced radiation response on hepatoma cells. It was found that the administration with resveratrol, a putative SirT1 activator, enhanced the resistance of HepG2 cells against radiation-induced DNA damage of MN formation under hypoxia condition; while nicotinamide, a well-known SirT1 inhibitor, sensitized this radiation damage. Nevertheless, pretreatment of cells with 10058-F4, a specific inhibitor of c-Myc, almost eliminated the nicotinamide-induced radiosensitive effect. Further studies revealed that resveratrol inhibited c-Myc protein accumulation via up-regulation of SirT1 expression and deacetylase activity, and this loss of c-Myc protein was abolished by inhibiting its degradation in the presence of MG132, a potent inhibitor of proteasome. In contrast, nicotinamide attenuated c-Myc protein degradation induced by radiation under hypoxia through inhibition of SirT1 deacetylase activity. Our findings suggest that SirT1 could serve as a novel potent target of radiation-induced DNA damage and thus as a potential strategy to advance the efficiency of radiation therapy in hepatoma entities. (author)

  12. Marshal of the Royal Air Force Sir John Cotesworth Slessor and the Anglo-American Air Power Alliance, 1940-1945

    National Research Council Canada - National Science Library

    Connolly, Corvin

    2001-01-01

    .... He played a remarkable and extensive role in building the Anglo-American air power partnership as an air planner on the Royal Air Force Staff, the British Chiefs of Staff, and the Combined Chiefs of Staff...

  13. Is Elevating Sir John A. Macdonald Really Worth It? Hitting the Reset Button on Canada's Founding Narrative in the Classroom

    Science.gov (United States)

    Gaudry, Adam

    2017-01-01

    This special issue of "Canadian Social Studies," entitled "Monumental Mistakes? Confronting Difficult Pasts," has brought together a diverse range of scholars offering insights into discussions regarding removing or altering monuments, buildings, and other reminders of difficult histories. The editors have requested that…

  14. Fkh1 and Fkh2 associate with Sir2 to control CLB2 transcription under normal and oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Christian eLinke

    2013-07-01

    Full Text Available The Forkhead box family of transcription factors is evolutionary conserved from yeast to higher eukaryotes and its members are involved in many physiological processes including metabolism, DNA repair, cell cycle, stress resistance, apoptosis and aging. In budding yeast, four Forkhead transcription factors were identified, namely Fkh1, Fkh2, Fhl1, and Hcm1, which are implicated in chromatin silencing, cell cycle regulation and stress response. These factors impinge transcriptional regulation during cell cycle progression, and histone deacetylases play an essential role in this process, e.g. the nuclear localisation of Hcm1 depends on Sir2 activity, whereas Sin3/Rpd3 silence cell cycle specific gene transcription in G2/M phase. However, a direct involvement of Sir2 in Fkh1/Fkh2-dependent regulation of target genes is at present unknown. Here, we show that Fkh1 and Fkh2 associate with Sir2 in G1 and M phase, and that Fkh1/Fkh2-mediated activation of reporter genes is antagonized by Sir2. We further report that Sir2 overexpression strongly affects cell growth in an Fkh1/Fkh2-dependent manner. In addition, Sir2 regulates the expression of the mitotic cyclin Clb2 through Fkh1/Fkh2-mediated binding to the CLB2 promoter in G1 and M phase. We finally demonstrate that Sir2 is also enriched at the CLB2 promoter under stress conditions, and that the nuclear localization of Sir2 is dependent on Fkh1 and Fkh2. Taken together, our results show a functional interplay between Fkh1/Fkh2 and Sir2 suggesting a novel mechanism of cell cycle repression. Thus, in budding yeast, not only the regulation of G2/M gene expression but also the protective response against stress could be directly coordinated by Fkh1 and Fkh2.

  15. Loss of ADAM9 expression impairs β1 integrin endocytosis, focal adhesion formation and cancer cell migration

    DEFF Research Database (Denmark)

    Mygind, Kasper J; Schwarz, Jeanette; Sahgal, Pranshu

    2018-01-01

    knockdown increases β1 integrin levels through mechanisms that are independent of its protease activity. In ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins. Mechanistically, ADAM9 co-immunoprecipitates with β1 integrin......, and both internalization and subsequent degradation of β1 integrin are significantly decreased in ADAM9-silenced cells, with no effect on β1 integrin recycling. Accordingly, the formation of focal adhesions and actin stress fibres in ADAM9-silenced cells is altered, possibly explaining the reduction...

  16. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  17. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  18. Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

    Science.gov (United States)

    Seegar, Tom C M; Killingsworth, Lauren B; Saha, Nayanendu; Meyer, Peter A; Patra, Dhabaleswar; Zimmerman, Brandon; Janes, Peter W; Rubinstein, Eric; Nikolov, Dimitar B; Skiniotis, Georgios; Kruse, Andrew C; Blacklow, Stephen C

    2017-12-14

    Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Johns Hopkins Particulate Matter Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — The Johns Hopkins Particulate Matter Research Center will map health risks of PM across the US based on analyses of national databases on air pollution, mortality,...

  20. 2008 St. Johns County, FL Countywide Lidar

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Airborne terrestrial LiDAR was collected for St. Johns County, FL. System Parameters/Flight Plan. The LiDAR system acquisition parameters were developed based on a...

  1. John Dewey--Philosopher and Educational Reformer

    Science.gov (United States)

    Talebi, Kandan

    2015-01-01

    John Dewey was an American philosopher and educator, founder of the philosophical movement known as pragmatism, a pioneer in functional psychology, and a leader of the progressive movement in education in the United States.

  2. Vähesed head portfellihaldurid / John Mauldin

    Index Scriptorium Estoniae

    Mauldin, John

    2005-01-01

    USA investeerimisnõustaja olulisematest põhimõtetest ja -reeglitest portfellihaldurite valikul. Investeerimissüsteemi analüüsist, minevikutootluse väheolulisusest ja fondimaailmas ellujäämisvõimalustest. Vt. samas: John Maudlin

  3. John Bell and the Identical Twins

    CERN Multimedia

    1984-01-01

    A biographical profile of John S.Bell is presented based on extensive interviews the author had with Bell. Bell’s vierws on the quantum theory are presented along with a simple explanation of his idenity.

  4. Translating The Infinities by John Banville

    OpenAIRE

    Irene Abigail Piccinini

    2015-01-01

    Abstract - John Banville’s talent as a prose stylist is widely recognized. The polished elegance of his phrases constitutes a continuing and fascinating challenge for his translator, due to the intricacies of the source text, its manifold registers and lexical choices. In his novel The Infinities, in Italian Teoria degli Infiniti, John Banville takes cue from Kleist’s Amphytrion to devise a novel where classicality interweaves with science and science fiction through the invention of a world ...

  5. Would John Stuart Mill have regulated pornography?

    OpenAIRE

    McGlynn, C.; Ward, I.

    2014-01-01

    John Stuart Mill dominates contemporary pornography debates where he is routinely invoked as an authoritative defence against regulation. This article, by contrast, argues that a broader understanding of Mill's ethical liberalism, his utilitarianism, and his feminism casts doubt over such an assumption. New insights into Mill's approach to sex, sexual activity, and the regulation of prostitution reveal an altogether more nuanced and activist approach. We conclude that John Stuart Mill would a...

  6. Adam Smith's Concept of Labour: Value or Measure?

    OpenAIRE

    Adolfo Rodriguez-Herrera

    2014-01-01

    The terminology employed by Smith to refer to value and measure of value is used in his time with imprecision, which has led to different interpretations about his position on these issues. It is no coincidence that Smith is considered the father of the labour theory of value developed by David Ricardo and Karl Marx and simultaneously of the cost-of-production theory of value developed by John Stuart Mill and Alfred Marshall. This paper reviews the concepts developed by Smith to formulate his...

  7. Le continent noir du désir masculin : Colet et Flaubert, encore

    OpenAIRE

    Vinken, Barbara

    2010-01-01

    Il y a peu d’échanges de lettres qui surprennent le lecteur aussi douloureusement que celui entre Louise Colet et Gustave Flaubert. Rarement, l’espoir qui sommeille au fond de tout lecteur d’une histoire d’amour heureux fut à ce point frustré.Les études de Freud – un des plus grands sceptiques en matière d’amour – sur la vie sexuelle éclairent les vicissitudes du désir amoureux masculin. Les Lettres de Flaubert à Colet sont la mise en scène dramatique d’un désir qui suit les complications du ...

  8. Determination of the Geographical Origin of All Commercial Hake Species by Stable Isotope Ratio (SIR) Analysis.

    Science.gov (United States)

    Carrera, Mónica; Gallardo, José M

    2017-02-08

    The determination of the geographical origin of food products is relevant to comply with the legal regulations of traceability, to avoid food fraud, and to guarantee food quality and safety to the consumers. For these reasons, stable isotope ratio (SIR) analysis using an isotope ratio mass spectrometry (IRMS) instrument is one of the most useful techniques for evaluating food traceability and authenticity. The present study was aimed to determine, for the first time, the geographical origin for all commercial fish species belonging to the Merlucciidae family using SIR analysis of carbon (δ 13 C) and nitrogen (δ 15 N). The specific results enabled their clear classification according to the FAO (Food and Agriculture Organization of the United Nations) fishing areas, latitude, and geographical origin in the following six different clusters: European, North African, South African, North American, South American, and Australian hake species.

  9. Mutations that Allow SIR2 Orthologs to Function in a NAD+-Depleted Environment.

    Science.gov (United States)

    Ondracek, Caitlin R; Frappier, Vincent; Ringel, Alison E; Wolberger, Cynthia; Guarente, Leonard

    2017-03-07

    Sirtuin enzymes depend on NAD + to catalyze protein deacetylation. Therefore, the lowering of NAD + during aging leads to decreased sirtuin activity and may speed up aging processes in laboratory animals and humans. In this study, we used a genetic screen to identify two mutations in the catalytic domain of yeast Sir2 that allow the enzyme to function in an NAD + -depleted environment. These mutant enzymes give rise to a significant increase of yeast replicative lifespan and increase deacetylation by the Sir2 ortholog, SIRT1, in mammalian cells. Our data suggest that these mutations increase the stability of the conserved catalytic sirtuin domain, thereby increasing the catalytic efficiency of the mutant enzymes. Our approach to identifying sirtuin mutants that permit function in NAD + -limited environments may inform the design of small molecules that can maintain sirtuin activity in aging organisms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Sir Peter Medawar: science, creativity and the popularization of Karl Popper

    Science.gov (United States)

    Calver, Neil

    2013-01-01

    Sir Peter Medawar was respected by scientists and literati alike. It was perhaps not surprising, then, that he would choose to involve himself in the ‘two cultures’ debate of 1959 and beyond. The focus of his intervention was the philosophy of Sir Karl Popper. However, Medawar's Popper was not the guru of falsification familiar from philosophy textbooks. Medawar's distinctive interpretation of Popper treated him instead as the source of insights into the role of creativity and imagination in scientific inquiry. This paper traces the context for Medawar's adoption of Popperian philosophy, together with its application before the debate. It then examines, within the context of the debate itself, the way in which Medawar attempted to reconcile scientific inquiry with literary practice. Medawar became increasingly convinced that not only was induction epistemologically unsound, but it was also damaging to the public role of the scientist. His construction of Popperianism would, he envisaged, provide a worthy alternative for scientists’ self-image.

  11. PENETAPAN ‘ADAM WALI NIKAH OLEH PEJABAT KUA DI KOTA SEMARANG

    Directory of Open Access Journals (Sweden)

    Rokhmadi

    2016-10-01

    Full Text Available This article is result of the study that describes the determination concept of adam wali nikah by officials of the Religious Affairs Office (KUA in Semarang, on marriage guardian of an ineligible woman, that because of the bride’s birth is less than six months from her parents’ marriage. Having determined adam marriage guardians’ status, then KUA establishes that the marriage guardian is delegated to KUA officials in each region of Semarang. As for the basis used by those who determine the delegation for the reason of deficient condition of marriage guardians for a female to the KUA is the use of the legal basis contained in adam marriage guardians’ determination in the letter of Director General Guidance and Pilgrimage Affairs Number: D/ED/PW.01/03/1992, in which its position is under the Marriage Legislation No. 1 of 1974 and the Islamic Law Compilation (KHI.

  12. Identification and Function of a Novel Candidate Gene for Asthma:ADAM 33

    Directory of Open Access Journals (Sweden)

    John W. Holloway

    2005-01-01

    Full Text Available Asthma is a complex disorder of inflammation and remodelling largely restricted to the conducting airways. It is a disorder where there are major genetics and environmental factors that interact together to initiate and propagate the disease into a chronic relapsing disorder. Until recently the genetic factors involved in disease pathogenesis have been restricted to variants in known molecules involved in the inflammatory or remodelling pathways. In this review evidence is presented for a new susceptibility gene for asthma, ADAM 33, that was identified by positional cloning. It is suggested that ADAM 33 plays a key role in predisposing to reduced lung function and bronchial hyperresponsiveness characteristic of asthma. Through an understanding of the disease-related SNPs(in ADAM 33it may be possible, not only to identify a gene based diagnostic test, but also to focus attention on developing a new treatment that reverses remodelling changes.

  13. Gender Ideology in The Diary Of Adam And Eve by Mark Twain

    Directory of Open Access Journals (Sweden)

    Paramita Ayuningtyas

    2011-04-01

    Full Text Available This article aims to show that behind the new version of Genesis by Mark Twain in his novel The Diary of Adam and Eve, there are some patriarchal principles that appear in it. It can be seen from the characterizations of Adam and Eve. By using some concepts from feminism and also focusing on the context of the novel, the analysis shows that patriarchal stereotypes about gender are applied in constructing the characters of Adam and Eve. Not only the content, but the form of the diary is also analyzed with the same method, and the same result is found. Therefore, it can be concluded that in spite of his progressiveness, Mark Twain still held patriarchal values in re-interpreting the tale of human creation.   

  14. The Disintegrin and Metalloprotease ADAM12 Is Associated with TGF-β-Induced Epithelial to Mesenchymal Transition.

    Directory of Open Access Journals (Sweden)

    Michaël Ruff

    Full Text Available The increased expression of the Disintegrin and Metalloprotease ADAM12 has been associated with human cancers, however its role remain unclear. We have previously reported that ADAM12 expression is induced by the transforming growth factor, TGF-β and promotes TGF-β-dependent signaling through interaction with the type II receptor of TGF-β. Here we explore the implication of ADAM12 in TGF-β-mediated epithelial to mesenchymal transition (EMT, a key process in cancer progression. We show that ADAM12 expression is correlated with EMT markers in human breast cancer cell lines and biopsies. Using a non-malignant breast epithelial cell line (MCF10A, we demonstrate that TGF-β-induced EMT increases expression of the membrane-anchored ADAM12L long form. Importantly, ADAM12L overexpression in MCF10A is sufficient to induce loss of cell-cell contact, reorganization of actin cytoskeleton, up-regulation of EMT markers and chemoresistance. These effects are independent of the proteolytic activity but require the cytoplasmic tail and are specific of ADAM12L since overexpression of ADAM12S failed to induce similar changes. We further demonstrate that ADAM12L-dependent EMT is associated with increased phosphorylation of Smad3, Akt and ERK proteins. Conversely, inhibition of TGF-β receptors or ERK activities reverses ADAM12L-induced mesenchymal phenotype. Together our data demonstrate that ADAM12L is associated with EMT and contributes to TGF-β-dependent EMT by favoring both Smad-dependent and Smad-independent pathways.

  15. The threshold of a stochastic delayed SIR epidemic model with temporary immunity

    Science.gov (United States)

    Liu, Qun; Chen, Qingmei; Jiang, Daqing

    2016-05-01

    This paper is concerned with the asymptotic properties of a stochastic delayed SIR epidemic model with temporary immunity. Sufficient conditions for extinction and persistence in the mean of the epidemic are established. The threshold between persistence in the mean and extinction of the epidemic is obtained. Compared with the corresponding deterministic model, the threshold affected by the white noise is smaller than the basic reproduction number R0 of the deterministic system.

  16. Traveling waves in a delayed SIR model with nonlocal dispersal and nonlinear incidence

    Science.gov (United States)

    Zhang, Shou-Peng; Yang, Yun-Rui; Zhou, Yong-Hui

    2018-01-01

    This paper is concerned with traveling waves of a delayed SIR model with nonlocal dispersal and a general nonlinear incidence. The existence and nonexistence of traveling waves of the system are established respectively by Schauder's fixed point theorem and two-sided Laplace transform. It is also shown that the spread speed c is influenced by the dispersal rate of the infected individuals and the delay τ.

  17. Global analysis of multi-strains SIS, SIR and MSIR epidemic models

    OpenAIRE

    Bichara , Derdei; Iggidr , Abderrahman; Sallet , Gauthier

    2014-01-01

    International audience; We consider SIS, SIR and MSIR models with standard mass action and varying population, with $n$ different pathogen strains of an infectious disease. We also consider the same models with vertical transmission. We prove that under generic conditions a competitive exclusion principle holds. To each strain a basic reproduction ratio can be associated. It corresponds to the case where only this strain exists. The basic reproduction ratio of the complete system is the maxim...

  18. Competitive exclusion principle for SIS and SIR models with n strains

    OpenAIRE

    Bichara , Derdei; Iggidr , Abderrahman; Sallet , Gauthier

    2012-01-01

    We consider SIS and SIR models with standard mass action and varying population, with $n$ different pathogen strains of an infectious disease. We also consider the same models with vertical transmission. We prove that under generic conditions a competitive exclusion principle holds. To each strain a basic reproduction ratio can be associated. It corresponds to the case where only this strain exists. The basic reproduction ratio of the complete system is the maximum of each individual basic re...

  19. Design of power controller in CDMA system with power and SIR error minimization

    Institute of Scientific and Technical Information of China (English)

    Shulan KONG; Huanshui ZHANG; Zhaosheng ZHANG; Hongxia WANG

    2007-01-01

    In this paper, an uplink power control problem is considered for code division multiple access (CDMA) systems. A distributed algorithm is proposed based on linear quadratic optimal control theory. The proposed scheme minimizes the sum of the power and the error of signal-to-interference ratio (SIR). A power controller is designed by constructing an optimization problem of a stochastic linear quadratic type in Krein space and solving a Kalman filter problem.

  20. Analysis of Active Lava Flows on Kilauea Volcano, Hawaii, Using SIR-C Radar Correlation Measurements

    Science.gov (United States)

    Zebker, H. A.; Rosen, P.; Hensley, S.; Mouginis-Mark, P. J.

    1995-01-01

    Precise eruption rates of active pahoehoe lava flows on Kilauea volcano, Hawaii, have been determined using spaceborne radar data acquired by the Space Shuttle Imaging Radar-C (SIR-C). Measurement of the rate of lava flow advance, and the determination of the volume of new material erupted in a given period of time, are among the most important observations that can be made when studying a volcano.

  1. Dynamic Behavior for an SIRS Model with Nonlinear Incidence Rate and Treatment

    Directory of Open Access Journals (Sweden)

    Junhong Li

    2013-01-01

    Full Text Available This paper considers an SIRS model with nonlinear incidence rate and treatment. It is assumed that susceptible and infectious individuals have constant immigration rates. We investigate the existence of equilibrium and prove the global asymptotical stable results of the endemic equilibrium. We then obtained that the model undergoes a Hopf bifurcation and existences a limit cycle. Some numerical simulations are given to illustrate the analytical results.

  2. Thermal vacuum test of space equipment: tests of SIR-2 instrument Chandrayaan-1 mission

    Science.gov (United States)

    Sitek, P.

    2008-11-01

    We describe the reasons of proceeding Thermal-Vacuum tests for space electronic. We will answer on following questions: why teams are doing TV tests, what kind of phases should be simulated, which situations are the most critical during TV tests, what kind of results should be expected, which errors can be detect. As an example, will be shown TV-test of SIR-2 instrument for Chandrayaan-1 moon mission.

  3. Milestones in plant sulfur research on sulfur-induced-resistance (SIR in Europe

    Directory of Open Access Journals (Sweden)

    Elke eBloem

    2015-01-01

    Full Text Available Until the 1970´s of the last century sulfur (S was mainly regarded as a pollutant being the main contributor of acid rain, causing forest dieback in central Europe. When Clean Air Acts came into force at the start of the 1980´s SO2 contaminations in the air were consequently reduced within the next years. S changed from an unwanted pollutant into a lacking plant nutrient in agriculture since agricultural fields were no longer fertilized indirectly by industrial pollution. S deficiency was first noticed in Brassica crops that display an especially high S demand because of its content of S-containing secondary metabolites, the glucosinolates. In Scotland, where S depositions decreased even faster than in continental Europe, an increasing disease incidence with Pyrenopeziza brassicae was observed in oilseed rape in the beginning 1990´s and the concept of sulfur-induced-resistance (SIR was developed after a relationship between the S status and the disease incidence was uncovered. Since then a lot of research was carried out to unravel the background of SIR in the metabolism of agricultural crops and to identify metabolites, enzymes and reactions, which are potentially activated by the S metabolism to combat fungal pathogens. The S status of the crop is affecting many different plant features such as color and scent of flowers, pigments in leaves, metabolite concentrations and the release of gaseous S compounds which are directly influencing the desirability of a crop for a variety of different organisms from microorganisms, over insects and slugs to the point of grazing animals.The present paper is an attempt to sum up the knowledge about the effect of the S nutritional status of agricultural crops on parameters that are directly related to their health status and by this to SIR. Milestones in SIR research are compiled, open questions are addressed and future projections were developed.

  4. Montaigne, Sir Ralph Bankes and other English readers of the Essais.

    OpenAIRE

    O'Brien, John

    2013-01-01

    This article deals with a hitherto unknown and unpublished early modern English manuscript account of Montaigne's Essais by Sir Ralph Bankes (1631?–77) of Kingston Lacy in Dorset. Bankes's account covers a range of features in Montaigne's work: crucial elements of self-portraiture such as judgement, but also his attitude to women and doctors. These characteristics are analysed and compared first with Montaigne's own pronouncements about the aspects Bankes selects and secondly with two other s...

  5. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Samat, N. A.; Ma' arof, S. H. Mohd Imam [Department of Mathematics, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak (Malaysia)

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  6. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    International Nuclear Information System (INIS)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-01-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases

  7. Simulation of emotional contagion using modified SIR model: A cellular automaton approach

    Science.gov (United States)

    Fu, Libi; Song, Weiguo; Lv, Wei; Lo, Siuming

    2014-07-01

    Emotion plays an important role in the decision-making of individuals in some emergency situations. The contagion of emotion may induce either normal or abnormal consolidated crowd behavior. This paper aims to simulate the dynamics of emotional contagion among crowds by modifying the epidemiological SIR model to a cellular automaton approach. This new cellular automaton model, entitled the “CA-SIRS model”, captures the dynamic process ‘susceptible-infected-recovered-susceptible', which is based on SIRS contagion in epidemiological theory. Moreover, in this new model, the process is integrated with individual movement. The simulation results of this model show that multiple waves and dynamical stability around a mean value will appear during emotion spreading. It was found that the proportion of initial infected individuals had little influence on the final stable proportion of infected population in a given system, and that infection frequency increased with an increase in the average crowd density. Our results further suggest that individual movement accelerates the spread speed of emotion and increases the stable proportion of infected population. Furthermore, decreasing the duration of an infection and the probability of reinfection can markedly reduce the number of infected individuals. It is hoped that this study will be helpful in crowd management and evacuation organization.

  8. Nicotinamide supplementation phenocopies SIR2 inactivation by modulating carbon metabolism and respiration during yeast chronological aging.

    Science.gov (United States)

    Orlandi, Ivan; Pellegrino Coppola, Damiano; Strippoli, Maurizio; Ronzulli, Rossella; Vai, Marina

    2017-01-01

    Nicotinamide (NAM), a form of vitamin B 3 , is a byproduct and noncompetitive inhibitor of the deacetylation reaction catalyzed by Sirtuins. These represent a family of evolutionarily conserved NAD + -dependent deacetylases that are well-known critical regulators of metabolism and aging and whose founding member is Sir2 of Saccharomyces cerevisiae. Here, we investigated the effects of NAM supplementation in the context of yeast chronological aging, the established model for studying aging of postmitotic quiescent mammalian cells. Our data show that NAM supplementation at the diauxic shift results in a phenocopy of chronologically aging sir2Δ cells. In fact, NAM-supplemented cells display the same chronological lifespan extension both in expired medium and extreme Calorie Restriction. Furthermore, NAM allows the cells to push their metabolism toward the same outcomes of sir2Δ cells by elevating the level of the acetylated Pck1. Both these cells have the same metabolic changes that concern not only anabolic pathways such as an increased gluconeogenesis but also respiratory activity in terms both of respiratory rate and state of respiration. In particular, they have a higher respiratory reserve capacity and a lower non-phosphorylating respiration that in concert with a low burden of superoxide anions can affect positively chronological aging. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    Science.gov (United States)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  10. Obituary: John W. Firor (1927-2007)

    Science.gov (United States)

    Gilman, Peter A.

    2009-12-01

    John W. Firor, a former Director of the High Altitude Observatory and the National Center for Atmospheric Research, and a founder of the Solar Physics Division of the American Astronomical Society, died of Alzheimer's disease in Pullman, Washington on November 5, 2007, he was 80. He was born in Athens Georgia on October 18, 1927, where his father was a professor of agricultural economics. John had an unusually diverse scientific career. His interest in physics and astrophysics began while serving in the army, during which time he was assigned to the Los Alamos National Laboratory, where he guarded highly radioactive materials (many have heard him describe how informal the protections were compared to later times). After his service he returned to college and graduated in physics from Georgia Tech in 1949. He received his Ph.D. from the University of Chicago in 1954, writing his thesis on cosmic rays under John Simpson. John Firor would later remark that: "If you needed cosmic rays to actually do anything, you are sunk." That thought, partly in jest, may help explain his motivation for moving to so many new scientific and management pursuits. John moved from cosmic ray physics to radio astronomy (particularly of the Sun) when he began work at the Carnegie Institution of Washington's Department of Terrestrial Magnetism, where he remained until 1961. During this time, he met Walter Orr Roberts, then the Director of the High Altitude Observatory (HAO) in Boulder, Colorado. HAO was then affiliated with the University of Colorado. In 1959, a movement began to upgrade the atmospheric sciences in the United States by establishing a National Center, where the largest, most important atmospheric research problems could be addressed. Roberts became the first Director of NCAR, as well as the first president of the University Corporation for Atmospheric Research (UCAR), the consortium of universities that was commissioned to manage and staff the new Center. HAO became a

  11. Analysis of data acquired by Shuttle Imaging Radar SIR-A and Landsat Thematic Mapper over Baldwin County, Alabama

    Science.gov (United States)

    Wu, S.-T.

    1985-01-01

    Seasonally compatible data collected by SIR-A and by Landsat 4 TM over the lower coastal plain in Alabama were coregistered, forming a SIR-A/TM multichannel data set with 30 m x 30 m pixel size. Spectral signature plots and histogram analysis of the data were used to observe data characteristics. Radar returns from pine forest classes correlated highly with the tree ages, suggesting the potential utility of microwave remote sensing for forest biomass estimation. As compared with the TM-only data set, the use of SIR-A/TM data set improved classification accuracy of the seven land cover types studied. In addition, the SIR-A/TM classified data support previous finding by Engheta and Elachi (1982) that microwave data appear to be correlated with differing bottomland hardwood forest vegetation as associated with varying water regimens (i.e., wet versus dry).

  12. Paradise Lost: Difference Between Adam and Eve's Lament on Leaving Paradise - a Contrastive Analysis

    OpenAIRE

    Servín, Sara Torres

    2013-01-01

    The difference between Adam and Eve’s lament on leaving Paradise in Milton’s Paradise Lost is striking in its contrastive content and depth. This paper analyzes the difference that exists between the feelings and spiritual attitudes that Adam and Eve express on the occasion when they are informed by the angel Michael that they have to abandon the Garden of Eden. It is a comparison of their lament in order to understand the contrast of the two attitudes that Milton wove in the tapestry that Pa...

  13. Dr Adam Zamenhof (1888-1940) and his insight into ophthalmology.

    Science.gov (United States)

    Wincewicz, Andrzej; Sulkowska, Mariola; Lieberman, E James; Bakunowicz-Lazarczyk, Alina; Sulkowski, Stanislaw

    2009-02-01

    Adam Zamenhof was greatly influenced by his father, Ludwik Zamenhof, who designed the international language Esperanto. Like his father, he became an ophthalmologist and joined the Esperanto movement. He published in the field of ophthalmology and was soon chosen as head of an ophthalmology department. He subsequently became Chief of the Orthodox Jewish Hospital at Czystem in Warsaw. He was active in the leadership of the Bialystok-Warsaw Chamber of Medical Doctors. He perished in the Nazi Holocaust (Shoah) but all Zamenhof's ideals that Adam served as a doctor and social activist remain still alive.

  14. DYNAMIC ANALYSIS OF A CRIMPING DEVICE WITH MULTIPLE CAMS USING MSC ADAMS II

    Directory of Open Access Journals (Sweden)

    Gheorghe Popescu

    2012-05-01

    Full Text Available Through the present paper, the author presents the results of the dynamic analysis with MSC ADAMS of the mechanism with a crimping device with 12 tightening cams, designed and used in the technological process of assembly of the indigenous electrical detonators. In this sense, the mechanism with multiple cams is considered a mechanical system and is treated as an assembly of rigid bodies connected by mechanical connections and elastic elements. For shaping and simulation of the mechanism with multiple cams using ADAMS program, the author got through the following stages: construction of the pattern, its testing and simulation, validation, finishing, parametrization, optimization of the pattern.

  15. ANALYSIS WITH MSC ADAMS OF A 5-FINGER AND 3-PHALANX /FINGER UNDER-ACTUATEDMECHANICAL HAND

    Directory of Open Access Journals (Sweden)

    Gheorghe POPESCU

    2013-05-01

    Full Text Available This paper studies the analysis with MSC ADAMS of a 5-fingered and 3-phalanx/finger underactuatedmechanical hand, designed by the author to work on industrial robots. Moreover, in order to increasegrasping safety in the automated handling process, the author has fitted each finger with a locking sequence inthe final phase of grasping. Thus, the mechanism of mechanical hand is considered to be a mechanical systemand is treated like a set of rigid bodies connected by mechanical linkages and elastic elements. To model andsimulate this mechanism with MSC ADAMS programme, the author covered the following stages: constructionof the model, testing-simulation, validation, finishing, parameterization, and optimization

  16. Fenotipo grave en dos medio hermanas con síndrome de Adams Oliver

    OpenAIRE

    Sevilla-Montoya, Rosalba; Ríos-Flores, Braulio; Moreno-Verduzco, Elsa; Domínguez-Castro, Mauricio; Rivera-Pedroza, Carlos I; Aguinaga-Ríos, Dra. Mónica

    2014-01-01

    El síndrome de Adams Oliver (AOS) es una entidad heterogénea con defecto transverso terminal de extremidades (TTLD) y aplasia cutis congénita (ACC) con un amplio espectro fenotípico. Se han descrito diferentes modos de herencia en esta enfermedad; los defectos más graves se han asociado a un patrón autosómico recesivo (AR). Objetivo. presentar a una familia con dos medio hermanas con un fenotipo grave de Adams Oliver, con una madre sana. Reporte del caso: una mujer de 27 años de edad fue refe...

  17. A substrate-optimized electrophoretic mobility shift assay for ADAM12

    DEFF Research Database (Denmark)

    Kotzsch, Alexander; Skovgaard, Tine; Buus, Uwe

    2014-01-01

    long been investigated as pharmaceutical drug targets; however, due to lack of potency and in vivo side effects, none of the small-molecule inhibitors discovered so far has made it beyond clinical testing. Ongoing research on novel selective inhibitors of ADAMs requires reliable biochemical assays...... to validate molecular probes from large-scale screening efforts. Here we describe an electrophoretic mobility shift assay for ADAM12 based on the identification of an optimized peptide substrate that is characterized by excellent performance and reproducibility....

  18. Adam M. Reid: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology.

    Science.gov (United States)

    2015-11-01

    The APA/APAGS Award for Distinguished Graduate Student in Professional Psychology is awarded on an annual basis by the APA Board of Professional Affairs (BPA) and the American Psychological Association of Graduate Students (APAGS) to a graduate student who has demonstrated outstanding practice and application of psychology. One of the 2015 award winners is Adam M. Reid, who received this award "for his community service, in which he has integrated the highest standards of professional psychological clinical practice and science." Adam's award citation, biography, and a selected bibliography are presented here. (c) 2015 APA, all rights reserved).

  19. Hoarding symptoms among psychiatric outpatients: confirmatory factor analysis and psychometric properties of the Saving Inventory – Revised (SI-R

    Directory of Open Access Journals (Sweden)

    Siau Pheng Lee

    2016-10-01

    Full Text Available Abstract Background The growing interest in problematic hoarding as an independent clinical condition has led to the development of the Saving Inventory-Revised (SI-R to assess hoarding phenomenology. The SI-R is one of the most widely used instruments to measure hoarding symptoms; however, it lacks validation in non-Western samples. Methods The current study examined the construct, convergent, and discriminant validity of the SI-R among 500 outpatients at a psychiatric hospital in Singapore. The three-factor structure solution of the SI-R was fitted in a confirmatory factor analysis. Results The final model achieved mediocre fit (χ2 = 1026.02, df = 186; RMSEA = 0.095, SRMR = 0.06; CFI = 0.86; NNFI = 0.85. Two reverse-coded items (items 2 and 4 were removed due to insufficient factor loadings, resulting in the modified 21-item SI-R (SIR-21. Our findings indicate the need to further examine the construct validity of the SI-R, particularly in non-Western samples. Nonetheless, correlations with other hoarding-related constructs, such as anxiety (Beck Anxiety Inventory and depression (Beck Depression Inventory-II, supported the convergent and discriminant validity of the SIR-21 in our sample. Conclusions Findings in our current majority Chinese sample were consistent with previous observations from other Chinese samples. Implications were discussed from a cross-cultural perspective, such as cultural emphasis on saving for future use and overlap between the concepts of discarding and acquiring in Chinese samples. Future studies should also examine differences among other ethnic groups (e.g., Malay, Indian.

  20. ADAM10 mediates the house dust mite-induced release of chemokine ligand CCL20 by airway epithelium

    NARCIS (Netherlands)

    Post, S.; Rozeveld, D.; Jonker, M. R.; Bischoff, R.; van Oosterhout, A. J.; Heijink, I. H.

    2015-01-01

    Background: House dust mite (HDM) acts on the airway epithelium to induce airway inflammation in asthma. We previously showed that the ability of HDM to induce allergic sensitization in mice is related to airway epithelial CCL20 secretion. Objective: As a disintegrin and metalloprotease (ADAM)s have

  1. ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function

    DEFF Research Database (Denmark)

    Kawaguchi, Nobuko; Sundberg, Christina; Kveiborg, Marie

    2003-01-01

    -100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary...

  2. ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome

    DEFF Research Database (Denmark)

    Christiansen, Michael; Pihl, Kasper; Hedley, Paula L.

    2010-01-01

    BACKGROUND: ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12. MATERIALS AND METHODS...

  3. Sir James Reid and the Death of Queen Victoria: An Early Model for End-of-Life Care.

    Science.gov (United States)

    Abrams, Robert C

    2015-12-01

    An appraisal of the last ten days of Queen Victoria's life, viewed primarily from the perspective of her personal physician, Sir James Reid, is presented. Sir James' clinical encounters with his patient and the Royal Family are examined to reveal his strategic and medical thinking and gauge his level of success in basic palliative aims. It was found that the lack of effective medical interventions, tensions within the Royal Family, the importance of his post to Sir James' professional career, and the political ramifications unavoidably connected with the illness of a head of state, all presented challenges to Reid's efforts to ease the physical and emotional pain of Queen Victoria's dying. Key features of Sir James' approach included reliance on physician-patient and physician-family relationships, emphasis on emotional support for the patient, and the careful selection of interventions for the family. In the first years of the 20th century, an era when the contemporary concepts of palliative care, hospice, and family dynamics did not exist, Sir James' management of the Queen's final illness suggested an early model for end-of-life care. By the end of Queen Victoria's life, Sir James was seen to have preserved his patient's comfort and dignity, at the same time advancing family and societal acceptance of the death of this matriarchal figure. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Yiyuan; Long, Jiaoyue; Chen, Jun; Jiang, Xuemei; Zhu, Jian; Jin, Yang; Lin, Feng; Zhong, Jun; Xu, Rong [Key Laboratory of Biorheological Science and Technology, Ministry of Education, and Bioengineering College, Chongqing University, Shapingba, Chongqing 400030 (China); Mao, Lizheng [Jiangsu Asialand Biomed-Technology Co. Ltd., Changzhou, Jiangsu 213164 (China); Deng, Linhong, E-mail: dlh@cczu.edu.cn [Key Laboratory of Biorheological Science and Technology, Ministry of Education, and Bioengineering College, Chongqing University, Shapingba, Chongqing 400030 (China); Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164 (China)

    2016-11-15

    A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression promotes

  5. Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

    International Nuclear Information System (INIS)

    Duan, Yiyuan; Long, Jiaoyue; Chen, Jun; Jiang, Xuemei; Zhu, Jian; Jin, Yang; Lin, Feng; Zhong, Jun; Xu, Rong; Mao, Lizheng; Deng, Linhong

    2016-01-01

    A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression promotes a

  6. Binding of ADAM12, a marker of skeletal muscle regeneration, to the muscle-specific actin-binding protein, alpha -actinin-2, is required for myoblast fusion

    DEFF Research Database (Denmark)

    Galliano, M F; Huet, C; Frygelius, J

    2000-01-01

    ADAM12 belongs to the transmembrane metalloprotease ADAM ("a disintegrin and metalloprotease") family. ADAM12 has been implicated in muscle cell differentiation and fusion, but its precise function remains unknown. Here, we show that ADAM12 is dramatically up-regulated in regenerated, newly formed...... of differentiation. Using the yeast two-hybrid screen, we found that the muscle-specific alpha-actinin-2 strongly binds to the cytoplasmic tail of ADAM12. In vitro binding assays with GST fusion proteins confirmed the specific interaction. The major binding site for alpha-actinin-2 was mapped to a short sequence...... in a dominant negative fashion by inhibiting fusion of C2C12 cells, whereas expression of a cytosolic ADAM12 lacking the major alpha-actinin-2 binding site had no effect on cell fusion. Our results suggest that interaction of ADAM12 with alpha-actinin-2 is important for ADAM12 function....

  7. Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity.

    Science.gov (United States)

    Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Elliott, Kathy; Wagner, Steven L; Moir, Robert D; Becker, K David; Tanzi, Rudolph E

    2009-10-15

    ADAM10, a member of a disintegrin and metalloprotease family, is an alpha-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated alpha-secretase activity of ADAM10 (>70% decrease), and elevated Abeta levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD.

  8. Obituary: John Louis Perdrix, 1926-2005

    Science.gov (United States)

    Orchiston, D. Wayne

    2006-12-01

    John Perdrix, astronomical historian and co-founder of the Journal of Astronomical History and Heritage, died on 27 June 2005. John Louis Perdrix was born in Adelaide, Australia, on 30 June 1926. After studying chemistry at Melbourne Technical College and working in industry, he joined the Commonwealth Scientific and Industrial Research Organisation's Division of Minerals and Geochemistry. In 1974 the Division relocated to the Western Australian capital, Perth, and John spent the rest of his working life there involved in geochemical research. From his teenage years John had a passion for astronomy, which he fine-tuned through the Astronomical Society of Victoria and the Victorian Branch of the British Astronomical Association. He was very active in both groups, serving as President of the former and Secretary/Treasurer of the latter. He was also an FRAS, and a member of the AAS, the BAA parent body, and the IAU (Commission 41)?no mean feat for an Australian amateur astronomer. Throughout his life, he was a strong advocate of close amateur-professional relations. John's main research interest was history of astronomy, and over the years he wrote a succession of research papers, mainly about aspects of Australian astronomy. His well-researched and neatly-illustrated papers on the Melbourne Observatory and the Great Melbourne Telescope are classics, and when the Observatory's future was in the balance they played a key role in the State Government's decision to convert this unique facility into a museum precinct. To support his research activities, John built up an amazing library that developed its own distinctive personality and quickly took over his house and garage before invading commercial storage facilities! Apart from writing papers, John had an even greater passion for editing and publishing. From 1985 to 1997 he produced the Australian Journal of Astronomy, and in 1998 this was replaced by the Journal of Astronomical History and Heritage (JAH2). Both

  9. Mehrkörpersimulation eines ebenen Koppelgetriebes mittels Matlab / ADAMS -Co-Simulation

    OpenAIRE

    Gollee, Christian; Troll, Clemens

    2017-01-01

    Mit Hilfe der Matlab/ADAMS-Co-Simulation wird ein ebenes Koppelgetriebe (5- Gelenk) untersucht und anschließend die Wirkpaarung mit einem Stückgut betrachtet. Dabei werden verschiedene Modellierungsstufen angewendet und die Simulationsergebnisse Messergebnissen vom Versuchsstand gegenübergestellt. Daneben wird die grundlegende Herangehensweise beim Einsatz dieser Simulationswerkzeuge erläutert.

  10. ADAM-17: a novel therapeutic target for triple negative breast cancer.

    LENUS (Irish Health Repository)

    McGowan, P M

    2013-02-01

    Validated targeted therapy is currently unavailable for patients with invasive breast cancer negative for oestrogen receptors, progesterone receptors and HER2 [i.e., those with triple-negative (TN) disease]. ADAM-17 is a protease involved in the activations of several ligands that bind to and promotes intracellular signalling from the EGFR\\/HER family of receptors.

  11. How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

    Science.gov (United States)

    Ortmann, Andreas

    1997-01-01

    Adam Smith's discussion of the payment modes of teachers and resulting consequences for the quality of teaching and process of curricular innovation are reviewed through the conceptual lens of modern agency theory. Smith's analysis of higher education in his day (eighteenth century) sheds light on faculty incentive and assessment problems that…

  12. Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

    Science.gov (United States)

    Purcell, William M.

    1986-01-01

    Offers a dissenting interpretation of Adam Smith's Lectures on Rhetoric and Belles Lettres and a more conservative perspective on Smith's significance to the history of rhetorical theory. Views the lectures as an historical commentary on literature and rhetoric from the perspective of an eighteenth-century lecturer. (JD)

  13. An Austrian (mis)reads Adam Smith: a critique of Rothbard as intellectual historian

    Czech Academy of Sciences Publication Activity Database

    Matthews, P. H.; Ortmann, Andreas

    2002-01-01

    Roč. 14, č. 3 (2002), s. 379-392 ISSN 0953-8259 Institutional research plan: CEZ:AV0Z7085904 Keywords : Adam Smith * Rothbard Subject RIV: AH - Economics http://search.ebscohost.com/login.aspx?direct=true&db=bth&AN=6998203&site=ehost-live

  14. Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

    Science.gov (United States)

    Winch, Christopher

    1998-01-01

    Examines and discusses two views of political economy: (1) the classical model of Adam Smith; and (2) the social capitalist model associated with Friedrich List. Explores two varieties of vocational education and training that emerge from a comparison of Smith's and List's ideas. (CMK)

  15. Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

    Science.gov (United States)

    Davis, Denis J.

    1981-01-01

    The foundation of factional pressures for upgrading educational credentials in the labor market is examined through a review of human capital and screening theories. The writings of Adam Smith are referenced to show that the claims of the beneficial effects of educational upgrading have been questioned for 200 years. (Author/MLW)

  16. Pastoral care and healing in Africa: Towards an Adamic Christological practical theology imagination for pastoral healing

    Directory of Open Access Journals (Sweden)

    Vhumani Magezi

    2016-11-01

    Full Text Available This article argues that the challenge and need for relevant ministry models is critical for effective Christian ministry and pastoral ministry as practical life ministry. It establishes an Adamic Christological model as a paradigm that provides a practical effective ministerial approach in Africa, particularly within the context of pastoral care and healing. This framework reveals Christ’s complete identification with African Christians in their contextual sufferings as the New Adam without compromising authentic gospel reality. In employing the Adamic Christological framework as the anchor for African pastoral and healing ministry, a model for African Christians’ daily response to their various contextual sufferings is constructed. This responsive model bridges the gap between the ascension of Christ and the interim period of Christianity by instituting God’s ongoing personal presence in believers’ suffering through the Holy Spirit (pneumatology as an encouraging and comforting reality that should enable Christians to cope in their suffering. It is argued that this Adamic Christological framework provides a practical theological model that contributes to healing and hope in pastoral care through practical knowing that impacts and imparts meaning in life.

  17. Making Socialists: Mary Bridges Adams and the Fight for Knowledge and Power, 1855-1939

    Science.gov (United States)

    Weiler, Kathleen

    2012-01-01

    This article presents a review of "Making socialists: Mary Bridges Adams and the fight for knowledge and power, 1855-1939," by Jane Martin. Jane Martin has explored the history of late-nineteenth-century and early-twentieth century-British women educational activists in numerous publications over the past two decades. Her first book,…

  18. Accident Damage Analysis Module (ADAM) – Technical Guidance, Software tool for Consequence Analysis calculations

    OpenAIRE

    FABBRI LUCIANO; BINDA MASSIMO; BRUINEN DE BRUIN YURI

    2017-01-01

    This report provides a technical description of the modelling and assumptions of the Accident Damage Analysis Module (ADAM) software application, which has been recently developed by the Joint Research Centre (JRC) of the European Commission (EC) to assess physical effects of an industrial accident resulting from an unintended release of a dangerous substance

  19. Adam Smith and the Educative Critique: A Response to My Commentators

    Science.gov (United States)

    Weinstein, Jack Russell

    2015-01-01

    This paper is both a response to the four reviewers in a special symposium on my book Adam Smith's Pluralism and a substantive discussion of philosophy of education. In it, I introduce what I call "the educative critique," a mode of analysis similar to Marxist, feminist, or postcolonial critiques, but focusing on the educative role of a…

  20. Association of ADAM33 gene S1 and S2 transmembrane domain ...

    African Journals Online (AJOL)

    Background: Chronic obstructive pulmonary disease (COPD) is defined as a disease characterised by partially reversible and progressive airflow limitation associated with an abnormal inflammatory response of the lung with systemic manifestation. COPD is influenced by both environmental and genetic factors. ADAM33 (a ...

  1. Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

    Science.gov (United States)

    Mundell, Jean

    1987-01-01

    Presents a lesson which calls upon students to compare Adam Smith's WEALTH OF NATIONS to James Madison's FEDERALIST #10 to see how the ancient concept of individual rights and liberties was used to describe both economic and governmental systems. Presents questions to provide the basis for comparison. (GEA)

  2. ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA

    DEFF Research Database (Denmark)

    Thodeti, Charles Kumar; Albrechtsen, Reidar; Grauslund, Morten

    2002-01-01

    The ADAMs (a disintegrin and metalloprotease) comprise a large family of multidomain proteins with cell-binding and metalloprotease activities. The ADAM12 cysteine-rich domain (rADAM12-cys) supports cell attachment using syndecan-4 as a primary cell surface receptor that subsequently triggers beta...

  3. Bathymetry (2011) for Fish Bay, St. John

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This image represents a LiDAR (Light Detection & Ranging) 0.3x0.3 meter resolution depth surface for Fish Bay, St. John in the U.S. Virgin Islands (USVI). The...

  4. The Bildungsroman in Cameroon Anglophone Literature: John ...

    African Journals Online (AJOL)

    This paper investigates the bildungsroman genre in postcolonial Cameroon Anglophone fiction through a textual analysis of John Nkemngong Nkengasong's Across the Mongolo and Margaret Afuh's Born before Her Time. It seeks to show that these two writers have borrowed a foreign genre and successfully manipulated ...

  5. Capitalism in Six Westerns by John Ford

    Science.gov (United States)

    Braun, Carlos Rodriguez

    2011-01-01

    The economic and institutional analysis of capitalism can be illustrated through John Ford's Westerns. This article focuses on six classics by Ford that show the move toward modern order, the creation of a new society, and the rule of law. Economic features are pervading, from property rights and contracts to markets, money, and trade. Ford has…

  6. John Dewey in the 21st Century

    Science.gov (United States)

    Williams, Morgan K.

    2017-01-01

    John Dewey was a pragmatist, progressivist, educator, philosopher, and social reformer (Gutek, 2014). Dewey's various roles greatly impacted education, and he was perhaps one of the most influential educational philosophers known to date (Theobald, 2009). Dewey's influence on education was evident in his theory about social learning; he believed…

  7. Preparing for Citizenship: Bring Back John Dewey

    Science.gov (United States)

    Pring, Richard

    2016-01-01

    The paper traces the development of citizenship in the curriculum in England since the 1960s, emerging particularly from the Crick report. It argues for lessons to be learnt from John Dewey's "Democracy and education", the centenary of which is being celebrated this year.

  8. We, John Dewey's Audience of Today

    Science.gov (United States)

    da Cunha, Marcus Vinicius

    2016-01-01

    This article suggests that John Dewey's "Democracy and Education" does not describe education in an existing society, but it conveys a utopia, in the sense coined by Mannheim: utopian thought aims at instigating actions towards the transformation of reality, intending to attain a better world in the future. Today's readers of Dewey (his…

  9. Jean Piaget's Debt to John Dewey

    Science.gov (United States)

    Tanner, Daniel

    2016-01-01

    Jean Piaget became a veritable institution unto himself in education and psychology, largely as the result of his developmental-stage theory advanced over the second quarter of the twentieth century. Not until Piaget was 73 did he make mention of John Dewey's work at Dewey's laboratory school, founded in 1894 at the University of Chicago. But here…

  10. John Deweys kritik af liberal education

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2017-01-01

    The paper deals with John Dewey's aversion against liberal education and his concern about a 'dual track' educational system separating liberal education and vocational education. It investigates the reason why Dewey maintains that the philosophical 'dualisms' culminate in the question on vocation....

  11. Astronaut John Glenn Enters Friendship 7

    Science.gov (United States)

    1962-01-01

    Astronaut John Glenn enters the Mercury spacecraft, Friendship 7, prior to the launch of MA-6 on February 20, 1961 and became the first American who orbited the Earth. The MA-6 mission was the first manned orbital flight boosted by the Mercury-Atlas vehicle, a modified Atlas ICBM (Intercontinental Ballistic Missile), lasted for five hours, and orbited the Earth three times.

  12. John R. Commons: Pioneer in Labor Economics.

    Science.gov (United States)

    Barbash, Jack

    1989-01-01

    John R. Commons has contributed in one way or another to pratically every piece of social and labor legislation that has been enacted in the twentieth century. He has made his mark on such diverse aspects of American labor as apprenticeship, vocational education, workers' compensation, and the administration of labor law. (Author/JOW)

  13. John Maynard Smith (1920-2004)

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 10; Issue 11. John Maynard Smith (1920-2004) - “One of the last Grand Evolutionary Theorists of the 20th Century”. Vidyanand Nanjundiah. General Article Volume 10 Issue 11 November 2005 pp 70-78 ...

  14. In Memoriam: Dr. Frank John Fenner

    Centers for Disease Control (CDC) Podcasts

    This podcast reflects on one of the greatest pioneers in virology, Dr. Frank John Fenner. Dr. Frederick Murphy, a member of EID's editorial board and the Institute of Medicine, and professor of Pathology at the University of Texas Medical Branch in Galveston, shares professional and personal stories of Dr. Frank Fenner.

  15. Obituary: John Leroy Climenhaga, 1916-2008

    Science.gov (United States)

    Scarfe, Colin

    2009-01-01

    John Leroy Climenhaga was born on 7 November 1916 on a farm some 10 km from Delisle, a small town on the Canadian prairies, located about 50 km south-west of Saskatoon, Saskatchewan, and died at his home in Victoria, British Columbia, on 27 May 2008. His parents, Reuben and Elizabeth (nee Bert) Climenhaga, were farming folk, and he carried their honest and open attitude to the world throughout his life. John was the seventh born, and last to die, of their ten children. His father also served as an ordained minister of the Brethren in Christ. In early adulthood, John worked on his father's farm, but then attended the University of Saskatchewan, obtaining a B.A. with Honors in Mathematics and Physics and an M.A. in Physics, in 1945 and 1949 respectively. Between these events he worked as a Physics Instructor at Regina College from 1946 to 1948. In 1949 Climenhaga joined the faculty of Victoria College, as one of only two physicists in a small institution that was then part of the University of British Columbia. He remained in Victoria for the rest of his career, playing a major role in the College's growth into a full-fledged university, complete with thriving graduate programs in physics and astronomy as well as in many other fields. He served as Head of the Physics Department during the 1960s, a period which saw the College become the University of Victoria, with a full undergraduate program in Physics, and campaigned successfully for the establishment of a program in Astronomy, which began in 1965. From 1969 until 1972 he held the position of Dean of Arts and Science, and championed the university's participation in the Tri-University Meson Facility, whose high-current medium-energy beam was ideal for the production and study of mesons and their physics. That period was a turbulent one in the university's history, but John's integrity and his balanced and fair-minded approach to conflicts were of immeasurable importance in steering the young institution through it

  16. El último libro de John Strachey

    Directory of Open Access Journals (Sweden)

    Helcías Martán Góngora

    1965-08-01

    Full Text Available Fue muy largo el sendero ideológico que hubo de recorrer el inglés John Strachey en la busqueda íntima de una respuesta a su inquirir constante. En su viaje interior escuchó, a la siniestra, también la voz de las sirenas socialistas.

  17. John Smith - eesti kunstnik / Ants Juske

    Index Scriptorium Estoniae

    Juske, Ants, 1956-2016

    2006-01-01

    Marko Mäetamme ja Kaido Ole kollektiivsest loomingust, mida esitatakse John Smithi autorinime all, mõnda ka salapärase J. Smithi nn. biograafiast. Illustratsiooniks J. Smith'i "Jumalate maailm I (fragment). Õli, lõuend, 2002. Erakogu

  18. John Dewey on Philosophy and Childhood

    Science.gov (United States)

    Gregory, Maughn; Granger, David

    2012-01-01

    John Dewey was not a philosopher of education in the now-traditional sense of a doctor of philosophy who examines educational ends, means, and controversies through the disciplinary lenses of epistemology, ethics, and political theory, or of agenda-driven schools such as existentialism, feminism, and critical theory. Rather, Dewey was both an…

  19. Bathymetry (2011) for Coral Bay, St. John

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This image represents a LiDAR (Light Detection & Ranging) 0.3x0.3 meter resolution depth surface for Coral Bay, St. John in the U.S. Virgin Islands (USVI). The...

  20. Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin

    Directory of Open Access Journals (Sweden)

    Slack Barbara E

    2011-05-01

    Full Text Available Abstract Background The amyloid precursor protein (APP is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease10 is also regulated by dynamin-dependent endocytosis. Results Transfection of human embryonic kidney (HEK cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A, increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Conclusions Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two

  1. Cosmosiin Increases ADAM10 Expression via Mechanisms Involving 5’UTR and PI3K Signaling

    Directory of Open Access Journals (Sweden)

    Zhuo Min

    2018-06-01

    Full Text Available The α-secretase “a disintegrin and metalloproteinase domain-containing protein” (ADAM10 is involved in the processing of amyloid precursor protein (APP. Upregulation of ADAM10 precludes the generation of neurotoxic β-amyloid protein (Aβ and represents a plausible therapeutic strategy for Alzheimer’s disease (AD. In this study, we explored compounds that can potentially promote the expression of ADAM10. Therefore, we performed high-throughput small-molecule screening in SH-SY5Y (human neuroblastoma cells that stably express a luciferase reporter gene driven by the ADAM10 promoter, including a portion of its 5’-untranslated region (5’UTR. This has led to the discovery of cosmosiin (apigenin 7-O-β-glucoside. Here, we report that in human cell lines (SH-SY5Y and HEK293, cosmosiin proportionally increased the levels of the immature and mature forms of the ADAM10 protein without altering its mRNA level. This effect was attenuated by translation inhibitors or by deleting the 5’UTR of ADAM10, suggesting that a translational mechanism was responsible for the increased levels of ADAM10. Luciferase deletion assays revealed that the first 144 nucleotides of the 5’UTR were necessary for mediating the cosmosiin-induced enhancement of ADAM10 expression in SH-SY5Y cells. Cosmosiin failed to increase the levels of the ADAM10 protein in murine cells, which lack native expression of the ADAM10 transcript containing the identified 5’UTR element. The potential signaling pathway may involve phosphatidylinositide 3-kinase (PI3K because pharmacological inhibition of PI3K attenuated the effect of cosmosiin on the expression of the ADAM10 protein. Finally, cosmosiin attenuated Aβ generation because the levels of Aβ40/42 in HEK-APP cells were significantly reduced after cosmosiin treatment. Collectively, we found that the first 144 nucleotides of the ADAM10 5’UTR, and PI3K signaling, are involved in cosmosiin-induced enhancement of the expression

  2. Preclinical pharmacological study on I-ADAM as a serotonin transporter ligand

    International Nuclear Information System (INIS)

    Wu Chunying; Lu Chunxiong; Jiang Quanfu; Zou Meifen; Chen Zhengping; Wang Songpei; Li Xiaomin; Zhang Tongxing; Zhu Junqing; Lin Xiangtong

    2004-01-01

    Objective: To evaluate the new ligand: I-2-( (22( (dimethylamino) methyl) phenyl) thio)-5- iodophenylamine (ADAM) as a serotonin imaging agent. Methods: Biological evaluations were performed in rats and mice. Results: Biodistribution studies in rats showed that the initial uptake of 131 I-ADAM in the brain was high (1.087%ID/organ at 2 min postinjection), and consistently displayed the highest binding (between 60-240 min postinjection) in hypothalamus, a region with the highest density of serotonin transporter (SERT). The specific binding [(TPCB)-1] of 131 I-ADAM in hypothalamus was 2.94, 3.03 and 3.09 at 60, 120 and 240 min postinjection, respectively. The (TPCB)-1 was significantly blocked by pretreatment with Paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug, Ketanserin, showed no blocking effect. The rat brain autoradiography and analysis showed that there was high 131 I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94 ± 0.39 to 1.30 ± 0.56 by pretreatment with Paroxetine at 60 min postinjection. Blood clearance kinetics was studied in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation was: C=3.6147·e -0.0725t + 1.0413 e -0.0028t . The thyroid uptake was 0.009 and 1.421% ID/organ at 2 min and 120 min postinjection, respectively, suggesting that in vivo deiodination maybe the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to human beings, assuming a body-weight of 50 kg. Conclusion: These data suggest that 131 I-ADAM may be useful for SPECT imaging of SERT binding sits in the brain. (authors)

  3. Obituary: John J. Hillman, 1938-2006

    Science.gov (United States)

    Chanover, Nancy

    2007-12-01

    John J. Hillman, a dedicated NASA civil servant, spectroscopist, astrophysicist, planetary scientist, and mentor, died on February 12, 2006 of ocular melanoma at his home in Columbia, Maryland. His professional and personal interests were wide-reaching and varied, and he devoted his career to the advancement of our understanding of the beauty and wonder in the world around us. His love of nature, art, and science made him a true Renaissance man. John was born in Fort Jay, New York, on November 22, 1938, and was raised in Washington, D.C. He received his B.S., M.S., and Ph.D. degrees in Physics from American University in 1967, 1970, and 1975, respectively. He began working at NASA's Goddard Space Flight Center, then in its infancy, in 1969, juggling a full-time position as a Research Physicist, the completion of his M.S. and Ph.D. degrees, and a young family. His background in molecular spectroscopy enabled him to apply his skills to numerous disciplines within NASA: infrared and radio astronomy; electronic, vibrational, and rotational structure of interstellar molecules; solar and stellar atmospheres; and planetary atmospheres. He published more than 70 journal papers in these disciplines. He was a frequent contributor to the Ohio State University International Symposium on Molecular Spectroscopy, and possessed a rare ability to bridge the gap between laboratory and remote sensing spectroscopy, bringing scientists from different disciplines together to understand our Universe. The last fifteen years of John's career were devoted to the development of acousto-optic tunable filter (AOTF) cameras. He championed this technology as a low-cost, low-power alternative to traditional imaging cameras for in situ or remotely sensed planetary exploration. It was within this context that I got to know John, and eventually worked closely with him on the demonstration and application of this technology for planetary science using ground-based telescopes in New Mexico, California

  4. The influence of percutaneous nephrolithotomy on human systemic stress response, SIRS and renal function.

    Science.gov (United States)

    Shen, Pengfei; Wei, Wuran; Yang, Xiaochun; Zeng, Hao; Li, Xiong; Yang, Jie; Wang, Jia; Huang, Jiaoti

    2010-10-01

    The objective of this study is to investigate the influences of percutaneous nephrolithotomy (PNL) and open surgery nephrolithotomy on the systemic stress response, SIRS and renal function. Forty patients with kidney calculi were enrolled in the study. Twenty cases were randomized to the PNL group and the other twenty cases to the open surgery group. Levels of C-reactive protein (CRP), interleukin-6(IL-6), β(2)-microglobulin (β(2)-MG), respiration rate, heart rate, body temperature and white blood cell counts were examined. CRP and IL-6 were measured in all patients pre-operatively and on post-operative days 1, 3 and 6, respectively. There was significant difference in their pre- and post-operation levels (P PNL group and 12 cases in open surgery group; there was significant difference between the two groups (P 0.05). Urine β(2)-MG levels were also measured. There was significant difference between pre- and the first day post-PNL (P PNL (P > 0.05). There was significant difference between pre- and first and third day post-open surgery (P 0.05). There was significant difference between two groups at the first, third and sixth days (P PNL group and open surgery group to some extent. The degree of stress response of PNL is lower than that of open surgery, proving the advantages of PNL with reference to serum immunology. There were cases in both the groups with SIRS, but the degree of SIRS in PNL group was lesser than the other group. Both the groups have no obvious effect on glomerular filtration function after operation and have effect on renal tubular reabsorption in the early stage after operation; but the recovery of the PNL group is faster than the open surgery group. It is thus shown that PNL is much safer and more feasible and has lesser effect on renal function.

  5. A class of stochastic delayed SIR epidemic models with generalized nonlinear incidence rate and temporary immunity

    Science.gov (United States)

    Fan, Kuangang; Zhang, Yan; Gao, Shujing; Wei, Xiang

    2017-09-01

    A class of SIR epidemic model with generalized nonlinear incidence rate is presented in this paper. Temporary immunity and stochastic perturbation are also considered. The existence and uniqueness of the global positive solution is achieved. Sufficient conditions guaranteeing the extinction and persistence of the epidemic disease are established. Moreover, the threshold behavior is discussed, and the threshold value R0 is obtained. We show that if R0 extinct with probability one, whereas if R0 > 1, then the system remains permanent in the mean.

  6. The threshold of a stochastic delayed SIR epidemic model with vaccination

    Science.gov (United States)

    Liu, Qun; Jiang, Daqing

    2016-11-01

    In this paper, we study the threshold dynamics of a stochastic delayed SIR epidemic model with vaccination. We obtain sufficient conditions for extinction and persistence in the mean of the epidemic. The threshold between persistence in the mean and extinction of the stochastic system is also obtained. Compared with the corresponding deterministic model, the threshold affected by the white noise is smaller than the basic reproduction number Rbar0 of the deterministic system. Results show that time delay has important effects on the persistence and extinction of the epidemic.

  7. Global stability of an SIR model with differential infectivity on complex networks

    Science.gov (United States)

    Yuan, Xinpeng; Wang, Fang; Xue, Yakui; Liu, Maoxing

    2018-06-01

    In this paper, an SIR model with birth and death on complex networks is analyzed, where infected individuals are divided into m groups according to their infection and contact between human is treated as a scale-free social network. We obtain the basic reproduction number R0 as well as the effects of various immunization schemes. The results indicate that the disease-free equilibrium is locally and globally asymptotically stable in some conditions, otherwise disease-free equilibrium is unstable and exists an unique endemic equilibrium that is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations and a promising way for infectious diseases control is suggested.

  8. Sir Charles Bell (1774-1842) and his contributions to early neurosurgery.

    Science.gov (United States)

    Tubbs, R Shane; Riech, Sheryl; Verma, Ketan; Mortazavi, Martin M; Loukas, Marios; Benninger, Brion; Cohen-Gadol, Aaron A

    2012-03-01

    The renowned surgeon, neuroanatomist, and artist Sir Charles Bell not only impacted the lives of his peers through his creative endeavors and passion for art, but also sparked noteworthy breakthroughs in the field of neuroscience. His empathetic nature and zest for life enabled him to develop an early proclivity for patient care. As a result of his innovative findings regarding sensory and motor nerves and the anatomical makeup of the brain, he accepted some of the most prestigious awards and received an honorable reputation in society. Bell is recognized for his diligence, perseverance, and his remarkable contributions to surgery. The present review will explore his contributions to the discipline now known as neurosurgery.

  9. Dynamics analysis of SIR epidemic model with correlation coefficients and clustering coefficient in networks.

    Science.gov (United States)

    Zhang, Juping; Yang, Chan; Jin, Zhen; Li, Jia

    2018-07-14

    In this paper, the correlation coefficients between nodes in states are used as dynamic variables, and we construct SIR epidemic dynamic models with correlation coefficients by using the pair approximation method in static networks and dynamic networks, respectively. Considering the clustering coefficient of the network, we analytically investigate the existence and the local asymptotic stability of each equilibrium of these models and derive threshold values for the prevalence of diseases. Additionally, we obtain two equivalent epidemic thresholds in dynamic networks, which are compared with the results of the mean field equations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth

    Science.gov (United States)

    Saha, Nayanendu; Eissman, Moritz F.; Xu, Kai; Llerena, Carmen; Kusebauch, Ulrike; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M.; Nikolov, Dimitar B.; Lackmann, Martin

    2016-01-01

    The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

  11. A New Reading of Shakespeare's King John.

    Science.gov (United States)

    Usher, Peter D.

    1995-12-01

    Shakespeare wrote King John c.1594, six years after the defeat of the Spanish Armada, and ~ 50 years after publication of the Copernican heliocentric hypothesis. It is said to be the most unhistorical of the History Plays, ``anomalous'', ``puzzling'', and ``odd'', and as such it has engendered far more than the customary range of interpretive opinion. I suggest that the play alerts Elizabethans not just to military and political threats, but to a changing cosmic world view, all especially threatening as they arise in Catholic countries. (a) Personification characterizes the play. John personifies the old order, while Arthur and the Dauphin's armies personify the new. I suggest that Shakespeare decenters King John just as Copernicus decentered the world. (b) Hubert menaces Arthur's eyes for a whole scene (4.1), but the need for such cruelty is not explained and is especially odd as Arthur is already under sentence of death (3.3.65-66). This hitherto unexplained anomaly suggests that the old order fears what the new might see. (c) Eleanor's confession is made only to Heaven and to her son the King (1.1.42-43), yet by echoing and word play the Messenger from France later reveals to John that he is privy to it (4.2.119-124). This circumstance has not been questioned heretofore. I suggest that the Messenger is like the wily Hermes (Mercury), chief communicator of the gods and patron of the sciences; by revealing that he moves in the highest circles, he tells John that he speaks with an authority that transcends even that of a king. The message from on high presages more than political change; it warns of a new cosmic and religious world order (d) Most agree that John is a weak king, so Shakespeare must have suspected flaws in the old ways. He would have known that Tycho Brahe's new star of 1572, the comet of 1577, and the 1576 model of his compatriot Thomas Digges, were shattering old ideas. (e) The tensions of the play are not resolved because in 1594 the new order was

  12. Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

    Science.gov (United States)

    Schmitt, Ulrich; Hiemke, Christoph; Fahrenholz, Falk; Schroeder, Anja

    2006-12-15

    Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

  13. John Holt Stanway: Gone to Texas

    Science.gov (United States)

    Bryan, J.

    2008-01-01

    John Holt Stanway (1799Ð1872) was an amateur astronomer who lived in Manchester, England until 1845. He was in contact with the English Ôgrand amateurÕ astronomer, William Henry Smyth, who supported him for Fellowship of the Royal Astronomical Society and evidently advised him on how to build and equip an observatory. Apparently, Stanway had an observatory at Chorlton-cum-Hardy in 1837. In 1845, Stanway left for the United States in response to serious business problems. En route, he met Ashbel Smith, a representative of the government of the Republic of Texas, who convinced Stanway to go to Texas. There he changed his name to John H. Smythe Stanley and settled in Houston, where he re-established his observatory. He became a commercial photographer and wrote about astronomy and other scientific subjects in Houston newspapers until his death in 1872.

  14. In Memoriam: Dr. Frank John Fenner

    Centers for Disease Control (CDC) Podcasts

    2011-04-22

    This podcast reflects on one of the greatest pioneers in virology, Dr. Frank John Fenner. Dr. Frederick Murphy, a member of EID's editorial board and the Institute of Medicine, and professor of Pathology at the University of Texas Medical Branch in Galveston, shares professional and personal stories of Dr. Frank Fenner.  Created: 4/22/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 4/26/2011.

  15. 65 Year Birthday Celebration's Prof. John Ellis.

    CERN Multimedia

    Benoit Jeannet

    2011-01-01

    On 13 September, physicists from around the world joined John Ellis at a colloquium to celebrate his 65th birthday, and as he ended his long career as a distinguished CERN staff member and joins King’s College London. Here he is in the audience with fellow theorists, Nobel laureate Gerard ’t Hooft and Chris Llewellyn Smith, former director-general of CERN.

  16. John Dewey's Visits to Hawai'i

    Science.gov (United States)

    McEwan, Hunter

    2015-01-01

    John Dewey visited Hawai'i on three separate occasions. Of all three trips, by far the most important, as far as Dewey's influence on education in Hawai'i is concerned, was in 1899 when he came with his wife, Alice Chipman Dewey, to help launch the University Extension program in Honolulu. The Deweys' second trip was a very brief one--twenty years…

  17. Historical Footage of John Glenn Friendship 7

    Science.gov (United States)

    1962-01-01

    The Friendship mission launch on the 20th day of February marked the first time that an American attempts to orbit the Earth. Historical footage of John Glenn's suit up, ride out to the launch pad, countdown, liftoff, booster engine cutoff, and separation of the booster engine escape tower is shown. Views of the Earth, Glenn's manual control of the electrical fly-by wire system, and the recovery of the landing vehicle from the ocean are presented.

  18. O mercado como ordem social em Adam Smith, Walras e Hayek The market as a social order in Adam Smith , Walras and Hayek

    Directory of Open Access Journals (Sweden)

    Angela Ganem

    2012-04-01

    Full Text Available O objetivo do artigo é apresentar criticamente as teorias do mercado de Adam Smith, Leon Walras e F. A. Hayek, sublinhando o que se considera terem em comum, ou seja, a ideia de mercado como expressão da ordem social capitalista. Entende-se que esta concepção do mercado como ordem social aparece originariamente na história do pensamento econômico e na história das ideias através da solução de Adam Smith frente aos filósofos do contrato e avança, analiticamente, um século após, na tentativa de demonstração lógico-matemática da Teoria do Equilíbrio Geral em Walras para adquirir a souplesse teórica necessária a sua sobrevivência, no século XX, na teoria de Hayek, em que a história realizaria o autodesenvolvimento da ordem do mercado. O texto percorre as filiações filosóficas e as implicações metodológicas das teorias do mercado desses grandes autores, mostrando as formas diferenciadas que elas assumem: ordem natural para Smith, ordem racional para Walras e ordem espontânea para Hayek.The objective of the article is to critically present the liberal theories of Adam Smith, Leon Walras and F. A. Hayek, underlining what they have in common, that is, the idea of market as a general theory of society and the construction of scientific attributes that make possible the understanding of the supremacy of market order against other forms of social organization. It is assumed that this conception of market as social order appears originally in the history of economical thought and in the history of ideas through Adam Smith's solution against contract philosophers and that it advances analytically, a century later, in the attempt of logic-mathematic demonstration in Walras, to acquire the necessary theoretical souplesse for its survival, in the XX century, in the Darwinian adventures of the Austrian school libertarians, specially Hayek, for whom history would realize the self-development of the market. The text will traverse the

  19. Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

    Science.gov (United States)

    Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

    2014-02-01

    Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. [Sir Geoffrey Keynes 1887-1982. Surgical pioneer, medical historian, humanist].

    Science.gov (United States)

    Bergljung, Lars

    2005-01-01

    Sir Geoffrey Keynes (1887 - 1982), was a pioneer in the surgery of breast cancer and thymic deseases, n.b. in patients suffering from myastenia gravis. He strongly disapproved of the longstanding dogma of so called radical mastectomy in breast cancer, and advocated a more limited surgical approach, followed by radiation therapy. This was done more than fifty years before breastconserving surgery has become the therapy of choice and against considerable opposition from the surgical establishment of his days. He also became a pioneer in the surgical treatment of myastenia gravis by thymectomy, at a time when there was no real understanding of the pathophysiology of the disease and when considerable controversy existed as to the importance or non importance of concomitant tumour formation in the thymus. Besides being a busy surgeon Sir Geoffrey was a medical historian, writing the biography of among others William Harvey, a bibliographer with a special interest in the poet and artist William Blake and a bibliophil with a large book collection of great value to medical history.

  1. Investigating Environmentally Sustainable Transport Based on DALY weights and SIR Method

    Directory of Open Access Journals (Sweden)

    Hossein Nezamianpour Jahromi

    2012-09-01

    Full Text Available Accessibility is one of the main causes of well-being and growth in contemporary societies. Transportation is the backbone of accessibility systems that lead to the growth of economic and social networks and spatial dispersion of activities. Unfortunately, the adverse effects of transportation have a great impact on the natural and human environment. Since transportation is associated with fossil fuel combustion, it results in emissions of pollutants that cause damage to human health. To save the global eco-system, sustainable development has become an international priority. To deal with the sustainability of transportation systems is an important issue as testified by a growing number of initiatives framed to define and measure sustainability in transportation planning and infrastructure planning as well. The capability of environmental assessment as a sustainability instrument is well known. This study proposes a new approach to rank countries based on environmental sustainability development applying disability adjusted life year (DALY weights for transportation sector emissions. DALY weights consider actual impacts of pollutants on human health. By employing SIR method, a superiority and inferiority ranking method is presented for multiple criteria decision making, the sustainability ranking of a number of European countries is presented. Three various ranking methods extracted from SIR ranking method are discussed and the results and the correlation among them are demonstrated.

  2. New approaches to improve a WCDMA SIR estimator by employing different post-processing stages

    Directory of Open Access Journals (Sweden)

    Amnart Chaichoet

    2008-09-01

    Full Text Available For effective control of transmission power in WCDMA mobile systems, a good estimate of signal-to-interference ratio (SIR is needed. Conventionally, an adaptive SIR estimator employs a moving average (MA filter (Yoon et al., 2002 to encounter fading channel distortion. However, the resulting estimate seems to have high estimation error due to fluctuation in the channel variation. In this paper, an additional post-processing stage is proposed to improve the estimation accuracy by reducing the variation of the estimate. Four variations of post-processing stages, namely 1 a moving average (MA postfilter,2 an exponential moving average (EMA post-filter, 3 an IIR post-filter and 4 least-mean-squared (LMS adaptive post-filter, are proposed and their optimal performance in terms of root-mean-square error (RMSE are then compared by simulation. The results show the best comparable performance when the MA and LMS post-filter are used. However, the MA post-filter requires a lookup table of filter order for optimal performance at different channel conditions, while the LMS post-filter can be used conveniently without a lookup table.

  3. Medicinal use of earths and minerals from Hippocrates to Sir Hans Sloane and beyond.

    Science.gov (United States)

    Retsas, Spyros

    2012-12-01

    In 1931 two pharmaceutical drawers containing mineral specimens, belonging to Sir Hans Sloane, the 18th century collector, Royal Physician, President of the Royal Society and of the Royal College of Physicians of London, were found in the Department of Botany of the Natural History Museum (NHM) of London. The drawers, each divided into 49 compartments, contained a total of 107 mineral pharmaceutical specimens, some labelled as mercury or white arsenic. Their registration, identification with the Sloane Manuscript Catalogues and subsequent transfer to the Mineralogy department of the NHM where one of these drawers is now on public display, had been documented by 1935. In antiquity therapeutic empiricism attributed medicinal properties to animal products, plants and minerals, including the soil of specific geographic locations. This communication traces the medicinal use of certain earths and minerals, listed in Sir Hans Sloane's manuscript catalogues, to classical antiquity with a reference to Arsenic compounds, which in our time are finding application in the treatment of acute promyelocytic leukaemia and to Terra Lemnia, a celebrated antidote of repute spanning twenty centuries, also included in the Sloane collections.

  4. Influence of heat conductivity on the performance of RTV SIR coatings with different fillers

    Energy Technology Data Exchange (ETDEWEB)

    Siderakis, K [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, GR-26110 Patras (Greece); Agoris, D [High Voltage Laboratory, Department of Electrical and Computer Engineering, University of Patras, Greece, GR-26500, Rion, Greece (Greece); Gubanski, S [High Voltage Laboratory, Department of Electric Power Engineering, Chalmers University of Technology, S-41296, Gothenburg (Sweden)

    2005-10-07

    Room temperature vulcanized silicone rubber (RTV SIR) coatings are employed in order to improve the pollution performance of high voltage ceramic insulators by imparting surface hydrophobicity. In this paper, the performance of three RTV SIR coatings containing different fillers is investigated in a salt-fog test. Alumina trihydrate (ATH) and silica are the fillers included in the formulation, aiming to increase the material endurance to the energy supplied by the surface electrical activity during periods of hydrophobicity loss. The primary action of these fillers is to increase the material heat conductivity, i.e. the amount of energy conducted to the substrate. In addition, in the case of ATH relief is also achieved due to particle decomposition. The results indicate that for the compositions commercially available, where low amounts of fillers are used, and under the conditions of the test, ATH filled coatings performed better than the silica filled ones. This is attributed to ATH decomposition which further relieves the material structure and therefore decelerates material aging.

  5. Ut Pictura Poesis : dialéctica entre palabras e imagen en Sir William Sterling Maxwell

    Directory of Open Access Journals (Sweden)

    Hilary Macartney

    2002-01-01

    Full Text Available En el presente artículo se analiza la estrecha relación entre la historia del arte de Sir William Stirling Maxwell, su biblioteca y su colección artística. Este vínculo encierra la clave para la comprensión de su excepcional aportación a la historiografía del arte español. Sus diversas actividades, como historiador del arte, coleccionista de libros y cuadros, y director de ediciones privadas de libros raros, fueron todas manifestaciones de su gran fascinación por el paralelo entre la literatura y el arte, la palabra y la imagen. Tal relación se encuentra incluso en el esquema decorativo de su biblioteca.This article examines the remarkable unity between Sir William Stirling Maxwell's art history, his library and his art collection and argües that this relationship is the key to understanding his unique contribution to scholarship of Spanish art. In particular, it will be shown that his actlvities as an art historian, bibliophile, art collector and editor of prívate editions of rare books were all expressions of his fascination with the relationship between literature and art in general, and more specifically between word and image. Even the decorative scheme of his library emphasised this relationship.

  6. Filtering authentic sepsis arising in the ICU using administrative codes coupled to a SIRS screening protocol.

    Science.gov (United States)

    Sudduth, Christopher L; Overton, Elizabeth C; Lyu, Peter F; Rimawi, Ramzy H; Buchman, Timothy G

    2017-06-01

    Using administrative codes and minimal physiologic and laboratory data, we sought a high-specificity identification strategy for patients whose sepsis initially appeared during their ICU stay. We studied all patients discharged from an academic hospital between September 1, 2013 and October 31, 2014. Administrative codes and minimal physiologic and laboratory criteria were used to identify patients at high risk of developing the onset of sepsis in the ICU. Two clinicians then independently reviewed the patient record to verify that the screened-in patients appeared to become septic during their ICU admission. Clinical chart review verified sepsis in 437/466 ICU stays (93.8%). Of these 437 encounters, only 151 (34.6%) were admitted to the ICU with neither SIRS nor evidence of infection and therefore appeared to become septic during their ICU stay. Selected administrative codes coupled to SIRS criteria and applied to patients admitted to ICU can yield up to 94% authentic sepsis patients. However, only 1/3 of patients thus identified appeared to become septic during their ICU stay. Studies that depend on high-intensity monitoring for description of the time course of sepsis require clinician review and verification that sepsis initially appeared during the monitoring period. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The optimal dynamic immunization under a controlled heterogeneous node-based SIRS model

    Science.gov (United States)

    Yang, Lu-Xing; Draief, Moez; Yang, Xiaofan

    2016-05-01

    Dynamic immunizations, under which the state of the propagation network of electronic viruses can be changed by adjusting the control measures, are regarded as an alternative to static immunizations. This paper addresses the optimal dynamical immunization under the widely accepted SIRS assumption. First, based on a controlled heterogeneous node-based SIRS model, an optimal control problem capturing the optimal dynamical immunization is formulated. Second, the existence of an optimal dynamical immunization scheme is shown, and the corresponding optimality system is derived. Next, some numerical examples are given to show that an optimal immunization strategy can be worked out by numerically solving the optimality system, from which it is found that the network topology has a complex impact on the optimal immunization strategy. Finally, the difference between a payoff and the minimum payoff is estimated in terms of the deviation of the corresponding immunization strategy from the optimal immunization strategy. The proposed optimal immunization scheme is justified, because it can achieve a low level of infections at a low cost.

  8. A mixed SIR-SIS model to contain a virus spreading through networks with two degrees

    Science.gov (United States)

    Essouifi, Mohamed; Achahbar, Abdelfattah

    Due to the fact that the “nodes” and “links” of real networks are heterogeneous, to model computer viruses prevalence throughout the Internet, we borrow the idea of the reduced scale free network which was introduced recently. The purpose of this paper is to extend the previous deterministic two subchains of Susceptible-Infected-Susceptible (SIS) model into a mixed Susceptible-Infected-Recovered and Susceptible-Infected-Susceptible (SIR-SIS) model to contain the computer virus spreading over networks with two degrees. Moreover, we develop its stochastic counterpart. Due to the high protection and security taken for hubs class, we suggest to treat it by using SIR epidemic model rather than the SIS one. The analytical study reveals that the proposed model admits a stable viral equilibrium. Thus, it is shown numerically that the mean dynamic behavior of the stochastic model is in agreement with the deterministic one. Unlike the infection densities i2 and i which both tend to a viral equilibrium for both approaches as in the previous study, i1 tends to the virus-free equilibrium. Furthermore, since a proportion of infectives are recovered, the global infection density i is minimized. Therefore, the permanent presence of viruses in the network due to the lower-degree nodes class. Many suggestions are put forward for containing viruses propagation and minimizing their damages.

  9. Obituary: John Daniel Kraus, 1910-2004

    Science.gov (United States)

    Kraus, John D., Jr.; Marhefka, Ronald J.

    2005-12-01

    John Daniel Kraus, 94, of Delaware, Ohio, director of the Ohio State University "Big Ear" Radio Observatory, physicist, inventor, and environmentalist died 18 July 2004 at his home in Delaware, Ohio. He was born on 28 June 1910 in Ann Arbor, Michigan. He received a Bachelor of Science in 1930, a Master of Science in 1931, and a PhD in physics in 1933 (at 23 years of age), all from the University of Michigan, Ann Arbor. During the 1930s at Michigan, he was involved in physics projects, antenna consulting, and in atomic-particle-accelerator research using the University of Michigan's premier cyclotron. Throughout the late 1920s and the 1930s, John was an avid radio amateur with call sign W8JK. He was back on the air in the 1970s. In 2001 the amateur radio magazine CQ named him to the inaugural class of its Amateur Radio Hall of Fame. He developed many widely used innovative antennas. The "8JK closely spaced array" and the "corner reflector" were among his early designs. Edwin H. Armstrong wrote John in July 1941 indicating in part, "I have read with interest your article in the Proceedings of the Institute on the corner reflector...Please let me congratulate you on a very fine piece of work." Perhaps John's most famous invention, and a product of his intuitive reasoning process, is the helical antenna, widely used in space communications, on global positioning satellites, and for other applications. During World War II, John was in Washington, DC as a civilian scientist with the U.S. Navy responsible for "degaussing" the electromagnetic fields of steel ships to make them safe from magnetic mines. He also worked on radar countermeasures at Harvard University's Radio Research Laboratory. He received the U.S. Navy Meritorious Civilian Service Award for his war work. In 1946 he took a faculty position at Ohio State University, becoming professor in 1949, and retiring in 1980 as McDougal Professor Emeritus of Electrical Engineering and Astronomy. Even so, he never retired

  10. Quantitative measurement of Y90 brehmmstrahlung images after of Y90 Sir-Spheres implantation to assess lung shunting

    International Nuclear Information System (INIS)

    Forwood, Nicholas J.; Pocock, Nicholas; Shin, Jane; Young, Andy M; Szeto, Edwin R.

    2009-01-01

    Full text: Background: In clinical practice the dose of Y 9 0 Sir-Spheres is calculated using a pre injection of Tc 9 9 m MAA. There is however a potential difference due to the different properties of Tc 9 9 m MAA and Y 9 0 Sir-Spheres. We assessed the concordance of lung shunting of Y 9 0 Sir-Spheres estimated using Y 9 0 Bremsstrahlung imaging, compared to shunting assessed using Tc 9 9 m MAA. Methods: 15 Patients were evaluated using 150-200 MBq of Tc 9 9 m MAA injected into the hepatic artery under angiographic guidance. Whole body images were acquired using a LEAP collimator (window of 140 kEv+/-10%). The patients were subsequently treated with Y 9 0 Sir-Spheres. After microspheres injection, whole body brehmsstrahlung images were acquired using a medium energy collimator (window settings of 75 kEv +/- 20%). Tc 9 9 m MAA images were paired with their corresponding bremsstrahlung image and lung shunting in the stu ides calculated simultaneously. Each paired dataset was analyzed by 5 operators. Results: The mean lung shunting for Tc 9 9 m MAA acquisition was 3.32% (SD 2.03) which was significantly lower than the lung shunting using the Y 9 0 acquisitions: mean 16.19% (SD of 6.43). The Pearson coefficient was r = 0.62 (p 9 0 Sir-Spheres bremsstrahlung imaging is higher than that calculated by Tc 9 9 m MAA imaging. The relationship is not sufficiently strong to use bremsstahlung imaging to retrospectively quantify the lung-to-liver shunting as indicated using Tc 9 9 M AA. Further studies are underway to assess the reliability of Tc 9 9 m MAA lung uptake calculations in determining the dose of Y 9 0 Sir-Spheres.

  11. The Adam and Eve Robot Scientists for the Automated Discovery of Scientific Knowledge

    Science.gov (United States)

    King, Ross

    A Robot Scientist is a physically implemented robotic system that applies techniques from artificial intelligence to execute cycles of automated scientific experimentation. A Robot Scientist can automatically execute cycles of hypothesis formation, selection of efficient experiments to discriminate between hypotheses, execution of experiments using laboratory automation equipment, and analysis of results. The motivation for developing Robot Scientists is to better understand science, and to make scientific research more efficient. The Robot Scientist `Adam' was the first machine to autonomously discover scientific knowledge: both form and experimentally confirm novel hypotheses. Adam worked in the domain of yeast functional genomics. The Robot Scientist `Eve' was originally developed to automate early-stage drug development, with specific application to neglected tropical disease such as malaria, African sleeping sickness, etc. We are now adapting Eve to work with on cancer. We are also teaching Eve to autonomously extract information from the scientific literature.

  12. Adam Smith e Francis Ysidro Edgeworth: uma crítica do utilitarismo

    Directory of Open Access Journals (Sweden)

    Solange Regina Marin

    2012-01-01

    Full Text Available Sugerimos, nesse trabalho, a investigação das concepções de Adam Smith e a de Francis Ysidro Edgeworth do utilitarismo. Ambas as concepções foram utilizadas para desenvolver a Ciência Econômica. Porém, também apresentaram as limitações da teoria econômica, cujas fronteiras vislumbradas pelos autores remetem para a necessidade de avaliar as ações e condutas humanas com teoria moral diferente do utilitarismo. Entendemos que a teoria moral de Adam Smith, esquecida pela história do pensamento econômico, se apresenta como alternativa e, em decorrência, uma ideia promissora para aperfeiçoar o estudo das ações e condutas ditas econômicas.

  13. XOPÓS = Chorós : the dance of Adam

    DEFF Research Database (Denmark)

    Isar, Nicoletta

    is contained in the very title of the book: “the Dance of Adam.” This dance alone gives ontological meaning to the Byzantine subject, to the whole Byzantine ¿¿¿¿¿¿¿a. In this choral equation, Adam stands for the humanity all-embracing. The book reads ¿¿¿¿¿ from an interdisciplinary perspective, incorporating....... The originality of Isar’s Chorography stands in unveiling and enforcing an important paradigm (¿¿¿¿¿) in the Byzantine studies, which has deep roots in ancient practices. However, the Byzantine ¿¿¿¿¿ reflects a unique ontology, a new vision of the mode of being, creation and imagination in Byzantium. Its ontology...

  14. Cardboard Boxes and Invisible Fences: Homelessness and Public Space in City of Victoria v. Adams

    Directory of Open Access Journals (Sweden)

    Sarah Buhler

    2009-02-01

    Full Text Available This paper analyzes the recent decision of the British Columbia Supreme Court in City of Victoria v. Adams. Specifically, the paper considers three interlocking themes that emerge from the decision: (1 the nature of “public space” in the context of homelessness; (2 the autonomy of homeless individuals; and (3 the meaning and value of the “homeless body.” With reference to each theme, the paper explores how the judgment in Adams grapples with the purportedly normative “Law and Economics”- type arguments put forth by the City of Victoria. By drawing on insights from Critical Legal Studies theory and feminist jurisprudence, the paper shows that Adams subverts and destabilizes certain “normative” perspectives about public space and homelessness. However, the paper goes on to argue that in its conflation of “cardboard box” shelters with the “invisible fences” envisioned by Justice Wilson in Morgentaler, Adams presents an ambiguous victory for anti-poverty advocates. The paper argues that the decision may serve to increase barriers for a broader and more progressive understanding of section 7 in the future. Dans cet article, on analyse le jugement récent de la Cour Suprême de la Colombie Britannique dans City of Victoria v. Adams. Plus précisément, on considère trois thèmes qui ressortent du jugement et qui s’entrecroisent : (1 la nature d’«espace public» dans le contexte de l’itinérance; (2 l’autonomie des sans-abri; et (3 la signification et la valeur du «corps sans abri». En rapport avec chaque thème, on explore comment l’arrêt Adams compose avec les arguments supposément normatifs du genre «La Loi et l’Économie» avancés par la ville de Victoria. En s’inspirant de perceptions tirées de la théorie des Critical Legal Studies et de la jurisprudence féministe, l’auteure démontre que l’arrêt Adams subvertit et déséquilibre certaines perspectives «normatives» au sujet de l

  15. Adam M. Grant: Award for Distinguished Scientific Early Career Contributions to Psychology.

    Science.gov (United States)

    2011-11-01

    Presents Adam M. Grant, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For extensive, elegant, and programmatic research on the power of relational job design in enhancing employee motivation, productivity, and satisfaction; for creative and rigorous studies documenting the profound and surprising effects of connecting employees to their impact on others; for highlighting prosocial motivation, not only extrinsic and intrinsic motivations, as a key force behind employee behavior; and for demonstrating by example the feasibility and benefits of conducting field experiments, yielding studies rich in internal validity, external validity, and practical impact. In addition to his accomplishments, Adam M. Grant is known for his generosity as a scholar, teacher, and colleague." (PsycINFO Database Record (c) 2011 APA, all rights reserved). 2011 APA, all rights reserved

  16. Adam Smith ja tema "nähtamatu käsi" / Arno Köörna

    Index Scriptorium Estoniae

    Köörna, Arno, 1926-2017

    2004-01-01

    Majandusliku ja sotsiaalse efektiivsuse optimaalsest vahekorrast. Inglise majandusteoreetiku, liberaalse turumajandusteooria klassikalise esindaja Adam Smithi (1723-1790) põhiteosest "Uurimus rahvaste rikkuse olemusest ja põhjustest". "Inimnäolise" kapitalismi võimalikkusest Eestis

  17. Impulsive vaccination and dispersal on dynamics of an SIR epidemic model with restricting infected individuals boarding transports

    Science.gov (United States)

    Jiao, Jianjun; Cai, Shaohong; Li, Limei

    2016-05-01

    To understand the effect of impulsive vaccination and restricting infected individuals boarding transports on disease spread, we establish an SIR model with impulsive vaccination, impulsive dispersal and restricting infected individuals boarding transports. This SIR epidemic model for two regions, which are connected by transportation of non-infected individuals, portrays the evolvement of diseases. We prove that all solutions of the investigated system are uniformly ultimately bounded. We also prove that there exists globally asymptotically stable infection-free boundary periodic solution. The condition for permanence is discussed. It is concluded that the approach of impulsive vaccination and restricting infected individuals boarding transports provides reliable tactic basis for preventing disease spread.

  18. L’économie politique du désir dans le rituel et le militantisme au SriLanka

    Directory of Open Access Journals (Sweden)

    Wim Van Daele

    2013-03-01

    Full Text Available Le désir est au cœur des interactions complexes entre le développement et la religion. Cet article examine ses différentes expressions, comme étant une des préoccupations fondamentales de nombreuses religions, qui motivent à la fois le développement et les alternatives au développement. Au SriLanka, face au changement social, la forme néolibérale et mondialisée du développement est comprise et réinterprétée à travers des idiomes et des formations locales du désir. L’économie néolibérale cultive le désir et mène à un accroissement présumé de la présence des preta (fantômes affamés et avides qui se manifestent parfois au moment de la mort d’une personne. Les fantômes affamés, en tant que formations fétichisées du désir, trouvent un écho chez les consommateurs et les entrepreneurs, qui montrent unappétit insatiable vis-à-vis d’une richesse matérielle en constante croissance. Ainsi, l’apaisement ritualisé des fantômes affamés et le militantisme social de groupes tels que le Movement for National Land and Agricultural Reform (MONLAR sont clairement liés par leur préoccupation mutuelle face à l’insécurité existentielle des êtres humains et non humains, causée par un désir excessif et déséquilibré. L’action rituelle et le militantisme social divergent toutefois dans la formulation explicite de leurs préoccupations spécifiques concernant le désir. Le rituel matérialise et condense l’angoisse liée au désir, alors que le militantisme social décrit la fétichisation du désir en termes économiques, politiques et scientifiques plus abstraits.

  19. Comparison of manual and automated quantification methods of 123I-ADAM

    International Nuclear Information System (INIS)

    Kauppinen, T.; Keski-Rahkonen, A.; Sihvola, E.; Helsinki Univ. Central Hospital

    2005-01-01

    123 I-ADAM is a novel radioligand for imaging of the brain serotonin transporters (SERTs). Traditionally, the analysis of brain receptor studies has been based on observer-dependent manual region of interest definitions and visual interpretation. Our aim was to create a template for automated image registrations and volume of interest (VOI) quantification and to show that an automated quantification method of 123 I-ADAM is more repeatable than the manual method. Patients, methods: A template and a predefined VOI map was created from 123 I-ADAM scans done for healthy volunteers (n=15). Scans of another group of healthy persons (HS, n=12) and patients with bulimia nervosa (BN, n=10) were automatically fitted to the template and specific binding ratios (SBRs) were calculated by using the VOI map. Manual VOI definitions were done for the HS and BN groups by both one and two observers. The repeatability of the automated method was evaluated by using the BN group. Results: For the manual method, the interobserver coefficient of repeatability was 0.61 for the HS group and 1.00 for the BN group. The intra-observer coefficient of repeatability for the BN group was 0.70. For the automated method, the coefficient of repeatability was 0.13 for SBRs in midbrain. Conclusion: An automated quantification gives valuable information in addition to visual interpretation decreasing also the total image handling time and giving clear advantages for research work. An automated method for analysing 123 I-ADAM binding to the brain SERT gives repeatable results for fitting the studies to the template and for calculating SBRs, and could therefore replace manual methods. (orig.)

  20. Comparison of manual and automated quantification methods of {sup 123}I-ADAM

    Energy Technology Data Exchange (ETDEWEB)

    Kauppinen, T. [Helsinki Univ. Central Hospital (Finland). HUS Helsinki Medical Imaging Center; Helsinki Univ. Central Hospital (Finland). Division of Nuclear Medicine; Koskela, A.; Ahonen, A. [Helsinki Univ. Central Hospital (Finland). Division of Nuclear Medicine; Diemling, M. [Hermes Medical Solutions, Stockholm (Sweden); Keski-Rahkonen, A.; Sihvola, E. [Helsinki Univ. (Finland). Dept. of Public Health; Helsinki Univ. Central Hospital (Finland). Dept. of Psychiatry

    2005-07-01

    {sup 123}I-ADAM is a novel radioligand for imaging of the brain serotonin transporters (SERTs). Traditionally, the analysis of brain receptor studies has been based on observer-dependent manual region of interest definitions and visual interpretation. Our aim was to create a template for automated image registrations and volume of interest (VOI) quantification and to show that an automated quantification method of {sup 123}I-ADAM is more repeatable than the manual method. Patients, methods: A template and a predefined VOI map was created from {sup 123}I-ADAM scans done for healthy volunteers (n=15). Scans of another group of healthy persons (HS, n=12) and patients with bulimia nervosa (BN, n=10) were automatically fitted to the template and specific binding ratios (SBRs) were calculated by using the VOI map. Manual VOI definitions were done for the HS and BN groups by both one and two observers. The repeatability of the automated method was evaluated by using the BN group. Results: For the manual method, the interobserver coefficient of repeatability was 0.61 for the HS group and 1.00 for the BN group. The intra-observer coefficient of repeatability for the BN group was 0.70. For the automated method, the coefficient of repeatability was 0.13 for SBRs in midbrain. Conclusion: An automated quantification gives valuable information in addition to visual interpretation decreasing also the total image handling time and giving clear advantages for research work. An automated method for analysing {sup 123}I-ADAM binding to the brain SERT gives repeatable results for fitting the studies to the template and for calculating SBRs, and could therefore replace manual methods. (orig.)