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Sample records for adam fleming medal

  1. Luhmann Receives 2007 John Adam Fleming Medal

    NASA Astrophysics Data System (ADS)

    Russell, Christopher T.; Luhmann, Janet G.

    2008-02-01

    This year's John Adam Fleming medalist quickly established a reputation as an innovative and productive scientist with a broad range of interests. She made early and seminal contributions to aeronomy, cosmic rays, and magnetospheric and planetary physics. She contributed importantly to the understanding of the interaction of the solar wind with the atmosphere and magnetic fields of Mercury, Venus, Earth, and Mars. She has examined the behavior of planetary rings, the interaction of interstellar neutrals with heliospheric plasmas, as well as the interaction of planetary neutrals with the heliosphere. She has led in the study of the interaction of the moon Titan with the Saturn magnetosphere, and most recently she developed a vigorous solar physics effort, leading the implementation of the IMPACT particle and field package on the twin STEREO mission, now entering its second year of successful operation.

  2. Spiro K. Antiochos Receives 2013 John Adam Fleming Medal: Response

    NASA Astrophysics Data System (ADS)

    Antiochos, Spiro K.

    2014-01-01

    Thank you, Jim Klimchuk, for this far too generous citation, and thank you very much, my AGU colleagues, for honoring me with the Fleming Medal. When I consider the list of excellent scientists who have been awarded the Fleming Medal, I am humbled that you have included me in their company. I am especially proud that this award is from AGU because only later in my career did I change my science focus and join AGU. This was the best professional decision I have ever made. As a result, I have met many wonderful colleagues. I've always loved doing research, but my colleagues in AGU have made it so much more enjoyable. Also, moving to AGU gave me the opportunity to participate in truly exciting science. My present position is that of senior scientist for space weather at NASA Goddard. It is interesting to note that the field of space weather science did not even exist when I started my career. I was very fortunate to be part of the beginning of a new field and, as a result, to be able to participate in the explosive advances of space weather science over the past 2 decades.

  3. Mike Fuller Receives 2012 John Adam Fleming Medal: Response

    NASA Astrophysics Data System (ADS)

    Fuller, Mike

    2013-01-01

    Thank you, Chris and Subir, for nominating me for the Fleming Medal and for your very kind comments on my research. In looking back over the medalists since 1962, it is hard to believe that I could be lucky enough to join such distinguished company. Yet, I have been very lucky through life. First, I was lucky to go to Christ's Hospital and Cambridge University. Second, my Aunt Marjorie married a physicist, Johnnie Clegg, who was an excellent teacher and inspiration for me. Third, to be born in England in the mid-1930s was to be a member of a fortunate generation of scientists. Providing one safely negotiated World War II, one joined the academic world at a time of great excitement, of expansion, and support for science.

  4. Dalgarno receives Fleming Medal

    NASA Astrophysics Data System (ADS)

    McElroy, Michael B.; Dalgarno, Alexander

    The John Adam Fleming Medal, given for original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, and related sciences, was presented to Alexander Dalgarno at the AGU Spring Meeting Honor Ceremony on May 31 in Baltimore. The award citation and Dalgarno's response are given here.

  5. Dessler receives Fleming Medal

    NASA Astrophysics Data System (ADS)

    Hill, Thomas W.; Dessler, Alex

    Alexander J. Dessler was presented with the John Adam Fleming Medal at the AGU Spring Meeting in Baltimore last May. The award recognizes original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, and related sciences. The citation was delivered by Thomas W. Hill.

  6. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Response from Adam C. Maloof

    NASA Astrophysics Data System (ADS)

    Maloof, Adam C.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  7. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Citation for Adam C. Maloof

    NASA Astrophysics Data System (ADS)

    Hoffman, Paul F.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  8. Fukushima to receive Smith Medal

    NASA Astrophysics Data System (ADS)

    The 1990 Waldo E. Smith Medal for extraordinary service to geophysics will be given to Naoshi Fukushima, who earned an international reputation for his pioneering work in geomagnetic disturbance and ionospheric electric currents. Now retired from the University of Tokyo, Japan, Fukushima is being cited for his public service to international geophysics, and, in particular, his contributions to the International Association of Geomagnetism and Aeronomy, of which he was Secretary General from September 1975 to August 1983.The Smith Medal will be presented as part of the AGU Fall Meeting Honors Night festivities, Wednesday, December 5, in San Francisco, Calif. Three James B. Macelwane Medals, the John Adam Fleming Medal, and the Maurice Ewing Medal will also be presented (see Eos, February 20, 1990, p. 294).

  9. Seismological medals

    USGS Publications Warehouse

    Schmidt, P.

    1987-01-01

    Seismic events are environmental events, so it is not surprising that mankind, in coming to terms with earthquakes, has tried to express his feelings about them in an artistic manner too. By understanding the topical importance of medals in seismological affairs, we can appreciate the hertiage of the past. 

  10. What if Fleming had not discovered penicillin?

    PubMed

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

    2014-09-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents. PMID:25183937

  11. Fleming, Williamina Paton Stevens (1857-1911)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Astronomer, born in Dundee, Scotland, emigrated to Boston with her parents and worked as a maid in the home of EDWARD PICKERING, the director of the Harvard Observatory. Unhappy with the work performed by his existing employees and declaring that his maid could do a better job, Pickering hired her for clerical work and mathematical calculations. Fleming devised a system of classifying stars accor...

  12. What if Fleming had not discovered penicillin?

    PubMed Central

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A.; Chinnathambi, Arunachalam

    2014-01-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called “supasulfas”, and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents. PMID:25183937

  13. What if Fleming had not discovered penicillin?

    PubMed

    Alharbi, Sulaiman Ali; Wainwright, Milton; Alahmadi, Tahani Awad; Salleeh, Hashim Bin; Faden, Asmaa A; Chinnathambi, Arunachalam

    2014-09-01

    What would have happened had Alexander Fleming not discovered penicillin in 1928? Perhaps the obvious answer is that, someone else would have discovered penicillin during 1930s and the Oxford group, would still have purified it sometime in the early 1940s. Here, however, in this counterfactual account of the penicillin story, it is argued that without Fleming, penicillin might still be undiscovered and the antibiotic age would never have dawned. As a result, many of the recent developments in medicine, such as organ transplantation, might have been delayed or, at best, made more hazardous. Penicillin might have come onto the scene a few years later but, had Fleming overlooked the discovery, it seems certain that penicillin would not have saved countless Allied lives, during and after D-Day. Instead of having enjoyed fifty and more years of the antibiotic age, it is argued here, that we would have had to rely upon highly developed sulphonamides, so-called "supasulfas", and other chemically-derived antibacterial drugs. Indeed, it might be the case that, even well into this new millennium, the antibiotic age has yet to dawn, and medicine is still waiting for someone to chance upon penicillin. Here we discuss what might have happened had Fleming not discovered penicillin and come to the conclusion that the medical armoury available today would have been far different and might have relied solely upon highly developed varieties of sulphonamides or similar, synthetic, non-antibiotic antibacterial agents.

  14. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Response from Nicolas Dauphas

    NASA Astrophysics Data System (ADS)

    Dauphas, Nicolas

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for “significant contributions to the geophysical sciences by an outstanding young scientist.”

  15. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Response from Tanja Bosak

    NASA Astrophysics Data System (ADS)

    Bosak, Tanja

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  16. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Citation for Christian Schoof

    NASA Astrophysics Data System (ADS)

    Clarke, Garry

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  17. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Citation for Tanja Bosak

    NASA Astrophysics Data System (ADS)

    Rothman, Daniel H.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  18. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Response from Christian Schoof

    NASA Astrophysics Data System (ADS)

    Schoof, Christian

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  19. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Citation for Nicolas Dauphas

    NASA Astrophysics Data System (ADS)

    Davis, Andrew M.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for “significant contributions to the geophysical sciences by an outstanding young scientist.”

  20. President Reagan Presents Medals

    NASA Technical Reports Server (NTRS)

    1981-01-01

    President Ronald Reagan presents astronaut John Young with the Congressional Space Medal of Honor as well as NASA's Distinguished Service Medal. Astronaut Robert C. Crippen also received the Distinguished Service Medal and Dr. Alan Lovelace was presented with the President's Citizens Medal. From left to right: President Ronald Reagan Astronaut, John Young Astronaut, Robert Crippen Dr. Alan Lovelace Vice President George Bush

  1. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Citation for Arlene M. Fiore

    NASA Astrophysics Data System (ADS)

    Levy, Hiram, II

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  2. Bosak, Dauphas, Fiore, Maloof, and Schoof receive 2011 James B. Macelwane medals: Response from Arlene M. Fiore

    NASA Astrophysics Data System (ADS)

    Fiore, Arlene M.

    2012-01-01

    Tanja Bosak, Nicolas Dauphas, Arlene M. Fiore, Adam C. Maloof, and Christian Schoof were awarded the 2011 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist."

  3. 100. MISSILE ORDNANCE TEST FIXTURE (FLEMING UNIT) ON NORTHEAST WALL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    100. MISSILE ORDNANCE TEST FIXTURE (FLEMING UNIT) ON NORTHEAST WALL OF LANDLINE INSTRUMENTATION ROOM (106), LSB (BLDG. 770) - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

  4. Anders receives Hess Medal

    NASA Astrophysics Data System (ADS)

    Cameron, A. G. W.; Anders, Edward

    Edward Anders was awarded the Harry H. Hess Medal at the AGU Spring Meeting Honors Ceremony on May 31 in Baltimore. The Hess Medal recognizes outstanding achievements in research in the constitution and evolution of Earth and its sister planets. The award citation and Anders' response are given here.

  5. Hanson receives Macelwane Medal

    NASA Astrophysics Data System (ADS)

    Ravishankara, A. R.; Hanson, David R.

    At the 1996 Spring Meeting in Baltimore, Maryland, David R. Hanson received the 1996 James B. Macelwane Medal, which recognizes significant contributions to the geophysical sciences by a young scientist of outstanding ability. The medal citation and Hanson's response are given here.

  6. John Ambrose Fleming and the Beginning of Electronics

    SciTech Connect

    Fred Dylla; Steve Corneliussen

    2004-11-01

    2004 was the centenary of John Ambrose Fleming's momentous patent on the thermionic diode that can be called the birth of electronics. The ''Edison effect'' was discovered in 1882; this was later shown to be the result of thermionic emission of electrons from a heated filament into a vacuum. Edison did not make any significant devices based on this discovery, and the effect was ignored for more than 8 years. In 1890 Fleming explained the effect and showed that the thermionic diode could be used as a rectifier. Fourteen years later Fleming filed his 1904 patent on the thermionic diode. It was the first public announcement of the electron tube; this revolutionized the development of radio and led to the invention of the thermionic triode by Lee de Forest in 1906. The background to these events will be described.

  7. Sir Alexander Fleming: Scottish researcher who discovered penicillin.

    PubMed

    Ligon, B Lee

    2004-01-01

    The discovery and development of penicillin changed the entire direction of approaches to treating infectious diseases and saved the lives of millions of people. Indeed, the development of penicillin was a watershed event in the battle against infectious diseases, and the individual who discovered it, Sir Alexander Fleming, remains a prominent individual in the annals of medical history. This article focuses primarily on the personal life of Alexander Fleming, an individual who had a remarkable diversity of interests and who made many contributions to science and medicine.

  8. National Medal of Science

    NASA Astrophysics Data System (ADS)

    Wendel, JoAnna

    2014-04-01

    The nation's highest honor for American scientists and engineers, the National Medal of Science is awarded annually by the president of the United States to individuals who have made outstanding contributions to or for the total impact of their work on the current state of chemical, physical, biological, social or behavioral sciences; mathematics; or engineering. Anyone can submit a nomination. Submit a short description of the nominee's contribution and three letters of support to http://www.nsf.gov/od/nms/medal.jsp by 1 May 2014.

  9. National Medal of Science

    NASA Astrophysics Data System (ADS)

    Nineteen scientists and engineers were awarded the nation's highest scientific honor, the National Medal of Science, by President Ronald Reagan in late February in a ceremony held in the East Room of the White House. Among the recipients were two AGU members.

  10. What's an Adam's Apple?

    MedlinePlus

    ... Help White House Lunch Recipes What's an Adam's Apple? KidsHealth > For Kids > What's an Adam's Apple? Print A A A Text Size You're ... the throat. This is what's called an Adam's apple. Everyone's larynx grows during puberty, but a girl's ...

  11. 58. Photographic copy of historic medal, The Yellow Fever Medal, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    58. Photographic copy of historic medal, The Yellow Fever Medal, presented to the Portsmouth Naval Hospital by the Town Council of Portsmouth, 1856. (Portsmouth Naval Shipyard Museum, Portsmouth, VA) - Portsmouth Naval Hospital, Hospital Building, Rixey Place, bounded by Williamson Drive, Holcomb Road, & The Circle, Portsmouth, Portsmouth, VA

  12. Vidale receives Macelwane Medal

    NASA Astrophysics Data System (ADS)

    Mooney, Walter; Vidale, John E.

    The James B. Macelwane Medal, which is given for significant contributions to the geophysical sciences by a young scientist of outstanding ability, was presented to John E. Vidale at the 1994 Fall Meeting Honors Ceremony on December 7, 1994, in San Francisco. The award citation and Vidale's response are given here.“Scientific discovery most often comes from the creative exploitation of newly available data to address long-standing problems. John Vidale, who shares the 1994 Macelwane Medal, has excelled in this regard. His contributions in seismological studies of Earth structure and earthquake sources have been an inspiration to geophysicists throughout the world. His numerous publications in the leading journals Nature and Science over the past 4 years already well exceeds the number of papers accepted by these two journals in a typical scientific career. John selects data like ripe fruit waiting to be plucked, and utilizes it wisely.

  13. Langley Medal awarded

    NASA Astrophysics Data System (ADS)

    Bell, Peter M.

    Robert Thomas Jones, senior scientist at the Ames Research Center, Mountain View, Calif., was awarded the distinguished Langley Medal by the Smithsonian Institution for his ‘extensive contributions in theoretical aerodynamics, particularly with regard to development of the swept wing, supersonic area rule and, more recently, the oblique wing.’ Jones is an internationally acclaimed expert on aerodynamics, optics, and biomechanics as well as an applied mathematician, astronomer, inventor, author, and violin maker.The Langley award has been given to just 16 recipients since it was established 73 years ago. Past recipients include Wilbur and Orville Wright, Charles Lindbergh, and Richard Byrd. Named for Samuel Pierpont Langley, aeronautical pioneer and third secretary of the Smithsonian, the medal honors ‘especially meritorious investigations in the field of aerospace science.’

  14. Why did the Fleming strain fail in penicillin industry?

    PubMed

    Rodríguez-Sáiz, Marta; Díez, Bruno; Barredo, José Luis

    2005-05-01

    Penicillin, discovered 75 years ago by Sir Alexander Fleming in Penicillium notatum, laid the foundations of modern antibiotic chemotherapy. Early work was carried out on the original Fleming strain, but it was later replaced by overproducing strains of Penicillium chrysogenum, which became the industrial penicillin producers. We show how a C(1357)-->T (A394V) change in the gene encoding PahA in P. chrysogenum may help to explain the drawback of P. notatum. PahA is a cytochrome P450 enzyme involved in the catabolism of phenylacetic acid (PA; a precursor of penicillin G). We expressed the pahA gene from P. notatum in P. chrysogenum obtaining transformants able to metabolize PA (P. chrysogenum does not), and observing penicillin production levels about fivefold lower than that of the parental strain. Our data thus show that a loss of function in P. chrysogenum PahA is directly related to penicillin overproduction, and support the historic choice of P. chrysogenum as the industrial producer of penicillin.

  15. 33 CFR 13.01-40 - Miniature medals and bars.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-40 Miniature medals and bars. (a) Miniature Gold and Silver Lifesaving Medals and bars...

  16. 33 CFR 13.01-40 - Miniature medals and bars.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-40 Miniature medals and bars. (a) Miniature Gold and Silver Lifesaving Medals and bars...

  17. 33 CFR 13.01-40 - Miniature medals and bars.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-40 Miniature medals and bars. (a) Miniature Gold and Silver Lifesaving Medals and bars...

  18. 33 CFR 13.01-40 - Miniature medals and bars.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-40 Miniature medals and bars. (a) Miniature Gold and Silver Lifesaving Medals and bars...

  19. 33 CFR 13.01-40 - Miniature medals and bars.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-40 Miniature medals and bars. (a) Miniature Gold and Silver Lifesaving Medals and bars...

  20. A Conversation with Adam Heller.

    PubMed

    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. A Conversation with Adam Heller.

    PubMed

    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. PMID:26247288

  2. Knauss Receives 2006 Waldo E. Smith Medal

    NASA Astrophysics Data System (ADS)

    Spinrad, Richard W.; Knauss, John A.

    2007-01-01

    John A. Knauss was awarded the Waldo E. Smith Medal at the AGU Fall Meeting honors ceremony, which was held on 13 December 2006 in San Francisco, Calif. The medal recognizes extraordinary service to geophysics.

  3. Gurnis, McComas receive Macelwane Medals

    NASA Astrophysics Data System (ADS)

    O'Connell, Richard; Gurnis, Michael; Burch, James L.; McComas, David J.

    Michael Gurnis and David J. McComas were honored as recipients of James B. Macelwane Medals at the AGU 1993 Spring Meeting in Baltimore last May. The medal recognizes significant contributions to the geophysical sciences by a young scientist of outstanding ability. Richard O'Connell presented Gurnis' medal, and James L. Burch presented McComas' medal. Citations and responses are presented below.

  4. Indian Peace Medals in American History.

    ERIC Educational Resources Information Center

    Prucha, Francis Paul

    Silver medals played an important role in American Indian policy for more than a century. Following a practice of the French, Spanish, and British in the New World, the United States government presented Indian peace medals to important chiefs and warriors as symbols of attachment to the new nation. In addition, the medals were marks of rank…

  5. Ansel Adams: early works

    NASA Astrophysics Data System (ADS)

    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.

  6. Solidification science in cast MMCs: The influence of merton flemings

    NASA Astrophysics Data System (ADS)

    Rohatgi, Pradeep; Asthana, Rajiv

    2001-09-01

    The solidification science of cast metalmatrix composites (MMC) evolved as a subset of the broad field of solidification of monolithic alloys pioneered by Merton Flemings and his students. As a result of advances in solidification, the cast MMC field has evolved from its early incarnation—employing empirical research to engineer novel materials using versatile and cost-effective casting techniques—to using solidification-science-based approaches to tailor advanced materials for application-specific needs. The current and emerging applications of cast MMCs in a variety of automotive, aerospace, electronic packaging, and consumer-good industries exemplify the maturity of the field and the materials. Innovations in composite-forming techniques and efforts at wider industrial acceptance of MMCs will undoubtedly continue. However, the scientific principles underlying the solidification microstructure evolution that governs the composite properties have become well established, to a great extent, due to Flemings’ early, pioneering work on monolithic alloys and some of his more recent studies on solidification of reinforced metals. This paper reviews some aspects of solidification of discontinuously reinforced cast metals that owe their current understanding to Flemings’ contributions, in particular, the scientific understanding of macro- and microsegregation, fluidity and rheology of multiphase slurries, and stircasting, semi-solid casting, and preform infiltration. Current research to develop and test prototype components made from cast composites, including Al-flyash, Cu-graphite, Al-graphite, Al-alumina, and SiC-Al, is also presented, along with directions for future research.

  7. RAS Awards and Prizes: RAS Awards 2009; Gold Medal: Prof. David Williams; Gold Medal: Prof. Eric Priest; Price Medal: Prof. Malcolm Sambridge; Eddington Medal: Prof. James Pringle

    NASA Astrophysics Data System (ADS)

    2009-02-01

    Each year the RAS recognizes outstanding achievement in astronomy and geophysics by the award of medals and prizes. Candidates are nominated by Fellows and the awards made by a committee of Fellows, ensuring that these scientists have earned the respect and admiration of their peers in the research community. The Gold Medal for Astronomy is awarded to Prof. David Williams of University College London. The Gold Medal for Geophysics is awarded to Prof. Eric Priest of the University of St Andrews. The Price Medal is awarded to Prof. Malcolm Sambridge of the Australian National University. The Eddington Medal is given to Prof. James Pringle of the University of Cambridge.

  8. 1983 William Bowie Medal to Syun-iti Akimoto

    NASA Astrophysics Data System (ADS)

    Liebermann, Robert C.; Akimoto, Syun-iti

    The 45th William Bowie Medal is awarded to Syun-iti Akimoto for his pioneering work in the application of high-pressure, high-temperature research to geophysical problems. It is a great honor and personal pleasure for me to present to you this warm and generous man, whom I have admired and respected for many years, to receive AGU's most prestigious award. Akimoto joins the ranks of other distinguished scientists in the field of mineral physics who have received the William Bowie Medal: Leason Adams in 1950, Francis Birch in 1960, and A. E. Ringwood in 1974.High-pressure geophysics research was virtually nonexistent in Japan before 1960. In the 22 years since he joined the faculty of the Institute for Solid State Physics (ISSP) of the University of Tokyo, Akimoto has played the leading role in building Japanese high-pressure research as applied to the earth's mantle up to the level where, according to Ted Ringwood, Japan leads the world. Ringwood further attests that, “Akimoto has accomplished this by the example of scientific excellence which he has set in all his research and by his generous encouragement of younger workers.”

  9. Was Adam a Real Person?

    ERIC Educational Resources Information Center

    Lamoureux, Denis O.

    2011-01-01

    Belief in the historicity of Adam has been held firmly throughout the history of the church. In the light of modern biblical criticism and the evolutionary sciences, some conservative Christians are now questioning whether or not Adam was a real person. This paper argues that the existence of Adam in the opening chapters of scripture reflects an…

  10. The Adams Family

    ERIC Educational Resources Information Center

    Douven, Igor; Verbrugge, Sara

    2010-01-01

    According to Adams's Thesis, the acceptability of an indicative conditional sentence goes by the conditional probability of its consequent given its antecedent. We test, for the first time, whether this thesis is descriptively correct and show that it is not; in particular, we show that it yields the wrong predictions for people's judgments of the…

  11. Alexander Fleming, citrated blood and penicillin: paths not pursued and applications delayed.

    PubMed

    Mortimer, P P

    2009-12-01

    Ninety years ago Alexander Fleming (later to discover penicillin) jointly wrote a description of the use of indirect transfusions of citrated blood at a World War 1 (WW1) base hospital. It was the longest series yet to be published, incorporating what was then a novel procedure for treating war casualties. Returning to civilian life Fleming, a qualified surgeon and bacteriologist, chose a different career path, and not until the wars of the late 1930s were the advances in transfusion in WW1 fully incorporated into the management of trauma and haemorrhage. Like penicillin, the benefits of indirect transfusion were only slowly realised.

  12. ADAM Proteases and Gastrointestinal Function.

    PubMed

    Jones, Jennifer C; Rustagi, Shelly; Dempsey, Peter J

    2016-01-01

    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis.

  13. ADAM Proteases and Gastrointestinal Function

    PubMed Central

    Jones, Jennifer C.; Rustagi, Shelly; Dempsey, Peter J.

    2016-01-01

    A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis. PMID:26667078

  14. Purdy Awarded 2006 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Purdy, G. Michael; Detrick, Robert S.

    2007-01-01

    G. Michael Purdy was awarded the Maurice Ewing Medal at the AGU Fall Meeting honors ceremony, which was held on 13 December 2006 in San Francisco, Calif. The medal recognizes significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering technology and instrumentation; or outstanding service to marine science.

  15. Seeking Nominations for COSPAR Awards and Medals

    NASA Astrophysics Data System (ADS)

    The Committee on Space Research (COSPAR) is seeking candidates to be nominated for COSPAR awards and medals. These awards and medal recognize the outstanding achievements of space scientists throughout the world in a number of areas. It is important to honor the contributions of your colleagues. Therefore, please take a moment to consider nominees for the following:

  16. Learning Resource Centres at Sir Sandford Fleming College. LRC Project Team Report.

    ERIC Educational Resources Information Center

    Markanen, Susan; And Others

    Developed by the Learning Resource Centres (LRC) Project Team at Sir Sanford Fleming College, in Ontario, Canada, this report presents a model for establishing LRCs at the college. The first section reviews the need for LRCs, including the provision of lifelong learning and expected funding decreases for traditional operations. The next sections…

  17. 33 CFR 13.01-45 - Replacement of medals and bars.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-45 Replacement of medals and bars. The Gold or Silver Lifesaving Medal or...

  18. 33 CFR 13.01-45 - Replacement of medals and bars.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-45 Replacement of medals and bars. The Gold or Silver Lifesaving Medal or...

  19. 33 CFR 13.01-45 - Replacement of medals and bars.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-45 Replacement of medals and bars. The Gold or Silver Lifesaving Medal or...

  20. 33 CFR 13.01-45 - Replacement of medals and bars.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-45 Replacement of medals and bars. The Gold or Silver Lifesaving Medal or...

  1. 33 CFR 13.01-45 - Replacement of medals and bars.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-45 Replacement of medals and bars. The Gold or Silver Lifesaving Medal or...

  2. [Hakim-Adams syndrome].

    PubMed

    Shamov, I A

    2015-01-01

    Hakim-Adams syndrome is little known, although quite common disease. The etiology is not fully clear. Pathogenetic mechanisms included the blockage of cerebrospinal fluid outflow along the upper lateral surface of the brain, development of hydrocephalus with the expansion of the brain ventricles while maintaining normotensive cerebrospinal fluid (CSF). Main manifestations are ataxia, apraxia, symptoms of dementia and urinary disturbances, up to incontinence. Diagnosis is based on clinical symptoms, exploratory lumbar and neuroimaging. Main treatment is ventriculoperitoneal (stomach) shunt placement for fluid drainage. Timely surgical intervention gives good results and improves quality of life of patients. PMID:26525816

  3. New Mathematical Dimensions: Adam's Story

    ERIC Educational Resources Information Center

    Manizade, Agida

    2009-01-01

    Adam, an 11th grader, was identified as gifted and accepted into a two week summer enrichment program. He signed up for "Geometry with Flash Programming." He had no prior programming experience but had a strong and healthy self-image as mathematics student. Although Adam had a positive attitude toward mathematics and saw himself as a successful…

  4. Changing Perceptions in "Adam Bede."

    ERIC Educational Resources Information Center

    Loges, Max L.

    From the very beginning of "Adam Bede," the idea of sight or perception is emphasized. Indeed by reference to a quotation from Wordsworth, George Eliot announces the purpose of the novel: to reveal clearly, to remove from the shade. While most of the characters in "Adam Bede" do not perceive events clearly and must have their erroneous opinions…

  5. The disintegrin-metalloproteinases ADAM9, ADAM12, and ADAM15 are upregulated in gastric cancer.

    PubMed

    Carl-McGrath, Stacy; Lendeckel, Uwe; Ebert, Matthias; Roessner, Albert; Röcken, Christoph

    2005-01-01

    The ADAMs (A disintegrin and metalloproteinase) are a family of cell-surface membrane glycoproteins, whose multidomain structure enables diverse roles in a wide range of cellular processes. Accumulating evidence associates an increased expression of individual ADAM family members with various types of cancer, and we investigated the possible involvement of ADAM9, 12 and 15 in the pathogenesis of gastric cancer (GC). Using immunohistochemistry and quantitative RT-PCR, we examined the transcription and expression pattern of ADAM9, 12, and 15 in GCs and the corresponding non-tumor tissue, and in GC cell lines (AGS, MKN45, MKN28, NCI-N87, KATOIII). All three ADAMs were found to be significantly upregulated in GC compared to non-neoplastic foveolar epithelium, with ADAM12 expression being higher in intestinal- than in diffuse-type tumors. In vitro proliferation assays were used to evaluate the effects of ADAM-specific antibodies on the growth of GC cell lines. The administration of anti-ADAM9 and anti-ADAM15 antibodies inhibited cell growth, whereas anti-ADAM12 enhanced the proliferation of the GC cell lines. ADAM9, 12 and 15 are implicated in the malignant growth of GC cells, perhaps via the interaction with adhesion molecules, or the proteolytic 'shedding' of signaling molecules and the consequent transactivation of their receptors, such as the epithelial growth factor receptor and its ligands. The resultant modulation of the tumor-host interface may contribute to the pathogenesis, development or progression of gastric cancer. PMID:15586220

  6. Wigner Medal 2010 - Laudatio for Michio Jimbo

    NASA Astrophysics Data System (ADS)

    Kielanowski, Piotr

    2011-03-01

    The purpose of the Wigner Medal is to recognize outstanding contributions to the understanding of physics through group theory. The Wigner Medal was established in 1977/78 and is administered by the Group Theory and Fundamental Physics Foundation, a publicly supported organization. The 2010 International Selection Committee consisting of J Patera (Canada) - Chairman, M del Olmo (Spain), W Schleich (Germany), J-B Zuber (France) and A Bohm (USA) awarded the 2010 Wigner Medal to Michio JimboUniversity of Tokyo for his introduction of quantum groups and his study of affine Lie algebras in connection with classical and quantum integrable systems. Further information about the Wigner Medal and the Laudatio for Professor Michio Jimbo, presented by Fedor Smirnov, are included in the PDF.

  7. National Medal of Science nominations sought

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-03-01

    The U.S. National Science Foundation (NSF) is accepting nominations for the 2013 National Medal of Science until 1 April 2013. Congress established the medal in 1959 as a presidential award for individuals "deserving of special recognition by reason of their outstanding contributions to knowledge in the physical, biological, mathematical, or engineering sciences." Later, Congress expanded the recognition to include the social and behavioral sciences. NSF notes, "We are especially interested in identifying women, members of minority groups, and persons with disabilities for consideration." More information is available at http://www.nsf.gov/od/nms/medal.jsp and http://www.nsf.gov/od/nms/nsf_2013nationalmedalofscience_callfornominations.pdf. For more details, contact the Medal of Science program manager at nms@nsf.gov or 703-292-8040.

  8. Speciation despite globally overlapping distributions in Penicillium chrysogenum: the population genetics of Alexander Fleming's lucky fungus.

    PubMed

    Henk, D A; Eagle, C E; Brown, K; Van Den Berg, M A; Dyer, P S; Peterson, S W; Fisher, M C

    2011-10-01

    Eighty years ago, Alexander Fleming described the antibiotic effects of a fungus that had contaminated his bacterial culture, kick starting the antimicrobial revolution. The fungus was later ascribed to a putatively globally distributed asexual species, Penicillium chrysogenum. Recently, the species has been shown to be genetically diverse, and possess mating-type genes. Here, phylogenetic and population genetic analyses show that this apparently ubiquitous fungus is actually composed of at least two genetically distinct species with only slight differences detected in physiology. We found each species in air and dust samples collected in and around St Mary's Hospital where Fleming worked. Genotyping of 30 markers across the genome showed that preserved fungal material from Fleming's laboratory was nearly identical to derived strains currently in culture collections and in the same distinct species as a wild progenitor strain of current penicillin producing industrial strains rather than the type species P. chrysogenum. Global samples of the two most common species were found to possess mating-type genes in a near 1:1 ratio, and show evidence of recombination with little geographic population subdivision evident. However, no hybridization was detected between the species despite an estimated time of divergence of less than 1MYA. Growth studies showed significant interspecific inhibition by P. chrysogenum of the other common species, suggesting that competition may facilitate species maintenance despite globally overlapping distributions. Results highlight under-recognized diversity even among the best-known fungal groups and the potential for speciation despite overlapping distribution.

  9. Armstrong Receives Space Medal of Honor

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Astronaut Neil A. Armstrong receives the first Congressional Space Medal of Honor from President Jimmy Carter, assisted by Captain Robert Peterson. Armstrong, one of six astronauts to be presented the medal during ceremonies held in the Vehicle Assembly Building (VAB), was awarded for his performance during the Gemini 8 mission and the Apollo 11 mission when he became the first human to set foot upon the Moon.

  10. Armstrong Awarded Space Medal of Honor

    NASA Technical Reports Server (NTRS)

    1978-01-01

    Astronaut Neil A. Armstrong receives the first Congressional Space Medal of Honor from President Jimmy Carter, assisted by Captain Robert Peterson. Armstrong, one of six astronauts to be presented the medal during ceremonies held in the Vehicle Assembly Building (VAB), was awarded for his performance during the Gemini 8 mission and the Apollo 11 mission when he became the first human to set foot upon the Moon.

  11. Hansen receives 2001 Roger Revelle Medal

    NASA Astrophysics Data System (ADS)

    Prather, Michael J.; Hansen, James E.

    James E. Hansen received the Roger Revelle Medal at the 2001 Fall Meeting Honors Ceremony on 12 December in San Francisco, California. The medal is given for outstanding contributions toward an understanding of the Earth's atmospheric processes, including its dynamics, chemistry, and radiation; the roles of atmosphere, atmosphere-ocean coupling, or atmosphere-land coupling in determining the climate, biogeochemical cycles, or other key elements of the integrated climate system.

  12. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci.

    PubMed

    Bahudhanapati, Harinath; Bhattacharya, Shashwati; Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species. PMID:26308360

  13. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci

    PubMed Central

    Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species. PMID:26308360

  14. Adam Smith and dependency.

    PubMed

    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. PMID:22712591

  15. Adam Smith and dependency.

    PubMed

    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.

  16. 28 CFR 0.12 - Young American Medals Committee.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Young American Medals Committee. 0.12... Office of the Attorney General § 0.12 Young American Medals Committee. There shall be in the Office of the Attorney General a Young American Medals Committee, which shall be composed of four members,...

  17. 28 CFR 0.12 - Young American Medals Committee.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Young American Medals Committee. 0.12... Office of the Attorney General § 0.12 Young American Medals Committee. There shall be in the Office of the Attorney General a Young American Medals Committee, which shall be composed of four members,...

  18. 28 CFR 0.12 - Young American Medals Committee.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Young American Medals Committee. 0.12... Office of the Attorney General § 0.12 Young American Medals Committee. There shall be in the Office of the Attorney General a Young American Medals Committee, which shall be composed of four members,...

  19. 14 CFR 1221.202 - Description of the medal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Description of the medal. 1221.202 Section 1221.202 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL AND OTHER... Description of the medal. The description of the Congressional Space Medal of Honor, which was designed by...

  20. 14 CFR 1221.202 - Description of the medal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Description of the medal. 1221.202 Section 1221.202 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL AND OTHER... Description of the medal. The description of the Congressional Space Medal of Honor, which was designed by...

  1. [Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology].

    PubMed

    Madaliński, Kazimierz

    2012-01-01

    Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses

  2. The ADAM environment and transputers

    NASA Technical Reports Server (NTRS)

    Kelly, B. D.; Stewart, J. M.; Mcnally, B. V.

    1992-01-01

    The ADAM environment is both used for data analysis by Starlink and for data acquisition by the UK-involved observatories in Australia, Hawaii, and the Canary Islands. ADAM was originally hosted under VAX/VMS but is now at an advanced stage of a Unix port. ADAM comprises a parameter system, hierarchical data system, noticeboard system, error handling system, and other components. Originally a multi-tasking single processor environment, it has been enhanced to a multiprocessor environment using local or wide area networking. The Royal Observatory Edinburgh is producing a transputer version of the ADAM kernel to allow instruments which make use of transputers for data acquisition/control to integrate more closely with the ADAM software running at the telescopes. Communication into the transputer system is based on Ethernet carrying TCP/IP, which eases development toward a network of mixed VMS/Unix/transputer Telescope systems. The transputer system is being applied to instruments under development for the UKIRT and JCMT telescopes.

  3. 33 CFR 13.01-5 - Gold and Silver Lifesaving Medals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Gold and Silver Lifesaving Medals... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-5 Gold and Silver Lifesaving Medals. Lifesaving Medals may be awarded to any person...

  4. 33 CFR 13.01-5 - Gold and Silver Lifesaving Medals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Gold and Silver Lifesaving Medals... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-5 Gold and Silver Lifesaving Medals. Lifesaving Medals may be awarded to any person...

  5. 33 CFR 13.01-5 - Gold and Silver Lifesaving Medals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Gold and Silver Lifesaving Medals... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-5 Gold and Silver Lifesaving Medals. Lifesaving Medals may be awarded to any person...

  6. 33 CFR 13.01-5 - Gold and Silver Lifesaving Medals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Gold and Silver Lifesaving Medals... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-5 Gold and Silver Lifesaving Medals. Lifesaving Medals may be awarded to any person...

  7. 33 CFR 13.01-5 - Gold and Silver Lifesaving Medals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Gold and Silver Lifesaving Medals... GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-5 Gold and Silver Lifesaving Medals. Lifesaving Medals may be awarded to any person...

  8. Franklin-Adams, John (1843-1912)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    English businessman and amateur astronomer; compiled the Franklin-Adams Photographic Atlas of Star Positions (1913). The Franklin-Adams camera was a 25 cm aperture, 10 degree field telescope, later re-erected in Johannesburg....

  9. ADAMS executive and operating system

    NASA Technical Reports Server (NTRS)

    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.

  10. Thatcher Receives 2004 Charles A. Whitten Medal

    NASA Astrophysics Data System (ADS)

    Stein, Ross

    2005-02-01

    Wayne Thatcher received the Whitten Medal at the 2004 Fall Meeting Honors Ceremony on 15 December, in San Francisco, California. The medal is given for outstanding achievement in research on the form and dynamics of the Earth and planets. Citation. Armed with geodesy, Wayne Thatcher has probed the behavior of great earthquakes, concentrating on the two sites where large events are frequent and the geodetic record is lush: the western United States and Japan. From this, he has garnered deep insights into the earthquake cycle-the pattern of strain accumulation and release of which an earthquake is only the most visible part.

  11. Gilbert receives 1999 William Bowie Medal

    NASA Astrophysics Data System (ADS)

    Turekian, Karl K.; Gilbert, J. Freeman

    J. Freeman Gilbert was awarded the William Bowie Medal at the AGU Spring Meeting Honors Ceremony, which was held on June 2, 1999, in Boston, Massachusetts. The medal recognizes outstanding contributions to fundamental geophysics and unselfish cooperation in research.Freeman Gilbert was a geophysical pioneer, even as a student at the Massachusetts Institute of Technology, where he used the Whirlwind computer to apply computational methods to seismic problems. Later at the Institute of Geophysics and Planetary Physics (IGPP),at the University of California, Los Angeles, where he began his professional university career, he wrote a series of papers on the computation of synthetic seismograms in simple media.

  12. Multigram-scale synthesis of l,d-heptoside using a Fleming-Tamao oxidation promoted by mercuric trifluoroacetate.

    PubMed

    Li, Tianlei; Tikad, Abdellatif; Durka, Maxime; Pan, Weidong; Vincent, Stéphane P

    2016-09-01

    An efficient multigram-scale synthesis of methyl 2,3,4,6-tetra-O-benzyl-l-glycero-α-d-manno-heptopyranoside from methyl 2,3,4-tri-O-benzyl-α-d-mannopyranoside is reported. It involves a sequence of Swern oxidation, Grignard addition and Fleming-Tamao reactions. The resulting scaffold was used as a precursor to design a small library of clickable l-heptosides. This study shows that the use of mercuric bistrifluoroacetate is required both to accelerate and to cleanly perform the Fleming-Tamao oxidation, without side-reactions. PMID:27450667

  13. 76 FR 68167 - National Medal of Technology and Innovation Nomination Evaluation Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Nomination... meeting. SUMMARY: The National Medal of Technology and Innovation (NMTI) Nomination Evaluation Committee... Medal of Technology and Innovation Program, United States Patent and Trademark Office, 600 Dulany...

  14. 75 FR 69631 - National Medal of Technology and Innovation Nomination Evaluation Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-15

    ... Patent and Trademark Office National Medal of Technology and Innovation Nomination Evaluation Committee.... SUMMARY: The National Medal of Technology and Innovation (NMTI) Nomination Evaluation Committee will meet... FURTHER INFORMATION CONTACT: Richard Maulsby, Program Manager, National Medal of Technology and...

  15. Children's Literature. Adams State College.

    ERIC Educational Resources Information Center

    Myers, Susan L.

    This is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The dual purpose of these modules is stated as follows: trying to understand children and their needs and becoming familiar with and developing criteria for evaluating children's literature. The objectives of the modules, which are…

  16. John Couch Adams, the astronomer.

    NASA Astrophysics Data System (ADS)

    Foster, N.

    1989-03-01

    The planet Neptune was discovered more than 140 years ago. The circumstances of the discovery gave rise to great controversy, and very nearly led to an international incident between Britain and France, but this was only one of John Couch Adams' many contributions to astronomical science.

  17. Psychology and the National Medal of Science

    ERIC Educational Resources Information Center

    Lowman, Robert P.; Benjamin, Ludy T., Jr.

    2012-01-01

    When Congress created the National Medal of Science in 1959 to be awarded by the president of the United States, psychology was not among the eligible sciences. A concerted lobbying effort in the late 1970s changed that situation, adding social and behavioral sciences to the listing of eligible disciplines. This article describes how the award…

  18. 75 FR 14257 - Pricing for Bronze Medals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... United States Mint Pricing for Bronze Medals AGENCY: United States Mint, Department of the Treasury. ACTION: Notice. SUMMARY: The United States Mint is announcing the price of the 1\\5/16\\- inch bronze... and availability can be found on the United States Mint Web site at http://www.usmint.gov ....

  19. Emeritus trio scoops the 2013 Dirac Medal

    NASA Astrophysics Data System (ADS)

    Dacey, James

    2013-09-01

    The 2013 Dirac Medal has been awarded to three scientists whose wide-ranging work has brought profound advances in cosmology, astrophysics and fundamental physics. Thomas Kibble, James Peebles and Martin Rees all receive the honour, which is bestowed annually by the Abdus Salam International Centre for Theoretical Physics (ICTP) in Trieste, Italy.

  20. Call-fleming syndrome (reversible cerebral artery vasoconstriction) and aneurysm associated with multiple recreational drug use.

    PubMed

    Drazin, Doniel; Alexander, Michael J

    2013-01-01

    Drug abuse represents a significant health issue. Evidence suggests that recreational drug use has a direct effect on the cerebral vasculature and is of greater concern in those with undiagnosed aneurysms or vascular malformations. The authors report a case of thunderclap headache with a negative head CT and equivocal lumbar puncture after a drug-fueled weekend. The patient underwent diagnostic cerebral angiogram which demonstrated multisegmental, distal areas of focal narrowing of the middle, anterior, posterior, and posterior inferior cerebral artery and an incidental aneurysm. It is often difficult to determine the exact origin of symptoms; thus we were left with a bit of a chicken or the egg debate, trying to decipher which part came first. Either the aneurysm ruptured with associated concomitant vasospasm or it is a case of Call-Fleming syndrome (reversible cerebral artery vasoconstriction) with an incidental aneurysm. The authors proposed their management and rationale of this complex case.

  1. ADAM 12: A Putative Marker of Oligodendrogliomas?

    PubMed Central

    Kanakis, Dimitrios; Lendeckel, Uwe; Theodosiou, Paraskevi; Dobrowolny, Henrik; Mawrin, Christian; Keilhoff, Gerburg; Bukowska, Alicia; Dietzmann, Knut; Bogerts, Bernhard; Bernstein, Hans-Gert

    2013-01-01

    ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours. PMID:23324579

  2. ADAM 12: a putative marker of oligodendrogliomas?

    PubMed

    Kanakis, Dimitrios; Lendeckel, Uwe; Theodosiou, Paraskevi; Dobrowolny, Henrik; Mawrin, Christian; Keilhoff, Gerburg; Bukowska, Alicia; Dietzmann, Knut; Bogerts, Bernhard; Bernstein, Hans-Gert

    2013-01-01

    ADAM 12 (meltrin alpha) belongs to a large family of molecules, consisting of members with both disintegrin and metalloproteinase properties. ADAMs have been implicated in several cell physiological processes including cell adhesion, cell fusion, proteolysis and signalling. ADAM 12 is widely expressed, including skeletal muscle, testis, bone, intestine, heart and kidney. In addition, a variety of tumours show elevated expression of ADAM12; among them being breast-, colon-, gastric- and lung-carcinoma. As to the brain, ADAM 12 has been shown previously to be expressed in rat and human oligodendrocytes. However, little is known about the expression of this protease in brain tumours. This study demonstrates the presence of ADAM 12 in non-neoplastic oligodendroglial cells of normal human brain as well as in neoplastic oligodendroglia and minigemistocytes arising from four pure oligodendrogliomas and three mixed oligoastrocytomas. Double stainings revealed a notable preference of ADAM 12 for the oligodendroglial over astroglial components. The results of immunohistochemistry are in accordance with the results obtained from the RT-PCR, which further demonstrated a mild difference concerning the mRNA concentration of ADAM 12 between similar grades of eight astrocytomas and eight oligodendrogliomas (namely four astrocytomas grade II versus four oligodendrogliomas grade II and four astrocytomas grade III versus four oligodendrogliomas grade III). Both cellular immunostaining for ADAM 12 and ADAM 12 mRNA content decrease with higher histologic grade of the tumour. Surprisingly, the latter parameter (ADAM12 mRNA) showed a significant opposite correlation to the degree of histologic tumour malignancy. From our data showing that ADAM 12 is highly expressed in, but not restricted to, oligodendrogliomas, we conclude that ADAM 12 immunohistochemistry may be a helpful tool in the diagnosis of brain tumours.

  3. ADAM17, shedding, TACE as therapeutic targets.

    PubMed

    Rose-John, Stefan

    2013-05-01

    ADAM17 has been molecularly cloned as the enzyme responsible for cleavage of the transmembrane protein TNFα (TNFα converting enzyme, TACE). Later it was realized that ADAM17 was also responsible for the processing of cell adhesion proteins, cytokine and growth factor receptors and many ligands of the EGF receptor. Since TNFα is a target of anti-inflammatory therapies, it was speculated that inhibition of ADAM17 might be a therapeutic strategy in the treatment of inflammation or inflammation associated cancer. Meanwhile it has been recognized that ADAM17 governs many vital functions in the body and loss of ADAM17 leads to severe defects in the skin and to high susceptibility of the intestine to inflammation. Here I summarize data on the physiologic role of ADAM17 and the feasibility of specific blockade of this enzyme.

  4. Morel Receives 2005 Maurice Ewing Medal

    NASA Astrophysics Data System (ADS)

    Schrag, Daniel P.; Morel, François M. M.

    2006-02-01

    François M. M. Morel received the Ewing Medal at the AGU Fall Meeting Honors Ceremony, which was held on 7 December 2005, in San Francisco, Calif. The medal is given for significant original contributions to the scientific understanding of the processes in the ocean; for the advancement of oceanographic engineering, technology, and instrumentation; and for outstanding service to marine sciences. François Morel has led the search to understand the role of metals in the ocean, starting with a focus on inorganic processes and aquatic chemistry, and leading to a blend of geochemistry, microbiology, biochemistry, and genetics. His influence comes from his research and from the way he has educated an entire community of scientists with his textbooks, with his teaching, and through his former students and postdocs who hold faculty positions at universities throughout the world.

  5. Geiss Receives 2005 William Bowie Medal

    NASA Astrophysics Data System (ADS)

    Gloeckler, George; Geiss, Johannes

    2006-01-01

    Johannes Geiss was awarded the 2005 William Bowie Medal at the AGU Fall Meeting Honors Ceremony, which was held on 7 December 2005 in San Francisco, Calif. The medal recognizes outstanding contributions to fundamental geophysics and unselfish cooperation in research. I am most pleased and honored to present this citation to Johannes Geiss, a truly great space scientist and investigator of the solar system and universe. His pioneering work, spanning over half a century, has paved the way toward understanding the physical world in which we live, its origins, and its destiny. He is a strong and effective advocate of science and ingenious in his ability to influence science policy and foster good science. Space limitations allow me to highlight only a few of Geiss's outstanding scientific accomplishments, service to science and society, and contributions to the conduct of science.

  6. ADAMS: AIRLAB data management system user's guide

    NASA Technical Reports Server (NTRS)

    Conrad, C. L.; Ingogly, W. F.; Lauterbach, L. A.

    1986-01-01

    The AIRLAB Data Management System (ADAMS) is an online environment that supports research at NASA's AIRLAB. ADAMS provides an easy to use interactive interface that eases the task of documenting and managing information about experiments and improves communication among project members. Data managed by ADAMS includes information about experiments, data sets produced, software and hardware available in AIRLAB as well as that used in a particular experiment, and an on-line engineer's notebook. The User's Guide provides an overview of the ADAMS system as well as details of the operations available within ADAMS. A tutorial section takes the user step-by-step through a typical ADAMS session. ADAMS runs under the VAX/VMS operating system and uses the ORACLE database management system and DEC/FMS (the Forms Management System). ADAMS can be run from any VAX connected via DECnet to the ORACLE host VAX. The ADAMS system is designed for simplicity, so interactions within the underlying data management system and communications network are hidden from the user.

  7. 33 CFR 13.01-30 - Description of Silver Lifesaving Medal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Description of Silver Lifesaving... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-30 Description of Silver Lifesaving Medal. (a) The Silver Lifesaving Medal...

  8. 33 CFR 13.01-30 - Description of Silver Lifesaving Medal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Description of Silver Lifesaving... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-30 Description of Silver Lifesaving Medal. (a) The Silver Lifesaving Medal...

  9. 77 FR 59992 - Announcement of Humanities Medal Design Competition Under the America COMPETES Reauthorization...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... ARTS AND THE HUMANITIES Announcement of Humanities Medal Design Competition Under the America COMPETES... Presidential medal, this notice announces the Humanities Medal Design Competition under Section 105 of the... Humanities (NEH) is seeking a new design for the National Humanities Medal, which is bestowed annually by...

  10. 33 CFR 13.01-25 - Description of Gold Lifesaving Medal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Description of Gold Lifesaving... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-25 Description of Gold Lifesaving Medal. (a) The Gold Lifesaving Medal is...

  11. 33 CFR 13.01-25 - Description of Gold Lifesaving Medal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Description of Gold Lifesaving... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-25 Description of Gold Lifesaving Medal. (a) The Gold Lifesaving Medal is...

  12. 33 CFR 13.01-25 - Description of Gold Lifesaving Medal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Description of Gold Lifesaving... SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals, Bars, and Miniatures § 13.01-25 Description of Gold Lifesaving Medal. (a) The Gold Lifesaving Medal is...

  13. Dick receives 2011 Harry H. Hess Medal: Response

    NASA Astrophysics Data System (ADS)

    Dick, Henry J. B.

    2012-01-01

    Henry J. B. Dick was awarded the 2011 Harry H. Hess Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "outstanding achievements in research on the constitution and evolution of Earth and other planets."

  14. Maria T. Zuber Receives 2012 Harry H. Hess Medal: Citation

    NASA Astrophysics Data System (ADS)

    Solomon, Sean C.

    2013-01-01

    Maria T. Zuber was awarded the 2012 Harry H. Hess Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is for "outstanding achievements in research on the constitution and evolution of Earth and other planets."

  15. Dick receives 2011 Harry H. Hess Medal: Citation

    NASA Astrophysics Data System (ADS)

    Niu, Yaoling

    2012-01-01

    Henry J. B. Dick was awarded the 2011 Harry H. Hess Medal at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. The medal is for "outstanding achievements in research on the constitution and evolution of Earth and other planets."

  16. 31 CFR 92.1 - Manufacture of medals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Manufacture of medals. 92.1 Section 92.1 Money and Finance: Treasury Regulations Relating to Money and Finance UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.1 Manufacture of medals. With the approval of...

  17. 28 CFR 0.12 - Young American Medals Committee.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Young American Medals Committee. 0.12 Section 0.12 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Office of the Attorney General § 0.12 Young American Medals Committee. There shall be in the Office...

  18. 28 CFR 0.12 - Young American Medals Committee.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Young American Medals Committee. 0.12 Section 0.12 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Office of the Attorney General § 0.12 Young American Medals Committee. There shall be in the Office...

  19. 31 CFR 92.1 - Manufacture of medals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.1 Manufacture of medals. With the approval of the Director of the Mint, dies for medals of a national character designated by Congress may be executed at the Philadelphia Mint, and struck in such field office of the...

  20. 31 CFR 92.1 - Manufacture of medals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.1 Manufacture of medals. With the approval of the Director of the Mint, dies for medals of a national character designated by Congress may be executed at the Philadelphia Mint, and struck in such field office of the...

  1. 31 CFR 92.1 - Manufacture of medals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.1 Manufacture of medals. With the approval of the Director of the Mint, dies for medals of a national character designated by Congress may be executed at the Philadelphia Mint, and struck in such field office of the...

  2. 31 CFR 92.1 - Manufacture of medals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.1 Manufacture of medals. With the approval of the Director of the Mint, dies for medals of a national character designated by Congress may be executed at the Philadelphia Mint, and struck in such field office of the...

  3. John Glenn: Presented with NASA Distinguished Service Medal

    NASA Technical Reports Server (NTRS)

    1963-01-01

    John Glenn tours with his family, meets JFK and is presented with the NASA distinguished Service Medal. From: The John Glenn Story: Summary of astronaut John Glenn's flying career, from naval aviation training to space flight. The Mercury project is featured as John Glenn flies the Friendship 7 spacecraft. President John F. Kennedy presents the NASA Distinguished service Medal to Astronaut John Glenn.

  4. The Readability of the Newbery Medal Books (1974-1986).

    ERIC Educational Resources Information Center

    Schafer, Paul J.

    Noting that research indicating Newbery Medal books are not popular with elementary students in spite of their unquestioned superiority in plot, characterization, and style, a study examined the readability level of Newbery Medal winners from 1974 to 1986. Three readability formulas were used to assess readability: Gunning's Fog Index, Fry…

  5. 2009 National Medal for Museum and Library Service

    ERIC Educational Resources Information Center

    Bowen, Katherine

    2009-01-01

    This paper features the winners of this year's National Medals for Museum and Library Service, the nation's highest honor for libraries and museums. The award celebrates libraries and museums that make a difference for individuals, families, and communities. Medal winners are selected from nationwide nominations for institutions that demonstrate…

  6. Lobell, Rickaby, and Vrugt Receive 2010 James B. Macelwane Medals

    NASA Astrophysics Data System (ADS)

    Gorelick, Steven M.; Lobell, David B.; Elderfield, Harry; Rickaby, Rosalind; Sorooshian, Soroosh; Vrugt, Jasper A.

    2011-03-01

    David B. Lobell, Rosalind E. Rickaby, and Jasper A. Vrugt were awarded the 2010 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 15 December 2010 in San Francisco, Calif. The medal is for “significant contributions to the geophysical sciences by an outstanding young scientist.”

  7. Adam receives Fred Whipple Award

    NASA Astrophysics Data System (ADS)

    McCord, Thomas B.; Adams, John B.

    John B. Adams was presented with the Fred Whipple Award at the AGU Fall Meeting in December in San Francisco, California. The award, established in 1989 by the Planetary Sciences Section, is presented to an individual who makes an outstanding contribution to the field of planetary science.In the beginning, scientists including Galileo studied the solar system by staring through a tube with glass elements called a telescope. This panchromatic instrument demonstrated existence and motion of objects and revealed features such as craters and clouds. However, it required approximately another 400 years to develop the physics and technology necessary to determine remotely the composition of these objects.

  8. 77 FR 14600 - Pricing for 2012 Kennedy Half-Dollar Bags and Rolls, Bronze Medals, the First Spouse Bronze Medal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... United States Mint Pricing for 2012 Kennedy Half-Dollar Bags and Rolls, Bronze Medals, the First Spouse Bronze Medal Set and the Birth Set AGENCY: United States Mint, Department of the Treasury. ACTION: Notice. SUMMARY: The United States Mint is announcing 2012 pricing for Kennedy Half-Dollar bags and rolls,...

  9. ADAMs family and relatives in cardiovascular physiology and pathology.

    PubMed

    Zhang, Pu; Shen, Mengcheng; Fernandez-Patron, Carlos; Kassiri, Zamaneh

    2016-04-01

    A disintegrin and metalloproteinases (ADAMs) are a family of membrane-bound proteases. ADAM-TSs (ADAMs with thrombospondin domains) are a close relative of ADAMs that are present in soluble form in the extracellular space. Dysregulated production or function of these enzymes has been associated with pathologies such as cancer, asthma, Alzheimer's and cardiovascular diseases. ADAMs contribute to angiogenesis, hypertrophy and apoptosis in a stimulus- and cell type-dependent manner. Among the ADAMs identified so far (34 in mouse, 21 in human), ADAMs 8, 9, 10, 12, 17 and 19 have been shown to be involved in cardiovascular development or cardiomyopathies; and among the 19 ADAM-TSs, ADAM-TS1, 5, 7 and 9 are important in development of the cardiovascular system, while ADAM-TS13 can contribute to vascular disorders. Meanwhile, there remain a number of ADAMs and ADAM-TSs whose function in the cardiovascular system has not been yet explored. The current knowledge about the role of ADAMs and ADAM-TSs in the cardiovascular pathologies is still quite limited. The most detailed studies have been performed in other cell types (e.g. cancer cells) and organs (nervous system) which can provide valuable insight into the potential functions of ADAMs and ADAM-TSs, their mechanism of action and therapeutic potentials in cardiomyopathies. Here, we review what is currently known about the structure and function of ADAMs and ADAM-TSs, and their roles in development, physiology and pathology of the cardiovascular system.

  10. Asteroid shape modelling with ADAM

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-08-01

    Technological advancements have made it possible to obtain highly detailed images of asteroids, yet 3-D shape reconstruction remains a challenge. Shape inversion is an ill-posed inverse problem as systematic errors, shadowing effects due to non-convex features, and the limitations of the imaging systems render the direct inversion impossible. Moreover, the coverage of one observation session alone is seldom sufficient for 3-D reconstruction, necessitating a method for the integration of widely different, complementary data sources into a coherent shape solution.We present a new 3-D shape reconstruction method for asteroid models. ADAM, an acronym for all-data asteroid modelling, is a general procedure for combining disk-resolved observational data into a shape model. ADAM handles all disk-resolved data in a uniform manner via 2-D Fourier Transform. Almost all disk-resolved data sources are supported: adaptive optics and other images, range-Doppler radar data, and thermal infrared interferometry.As case studies, we examine the shape of (41) Daphne using the adaptive optics images and photometry, and create a model of the asteroid 2000 ET70 from the range-Doppler radar images. Finally, we combine ALMA science verification data, adaptive optics images, occultations, and lightcurve data to study the shape of the large main-belt asteroid (3) Juno.

  11. Pellagra Pre-Goldberger: Rupert Blue, Fleming Sandwith, and The “Vitamine Hypothesis”

    PubMed Central

    Bryan, Charles S.; Mull, Shane R.

    2015-01-01

    The conquest of pellagra is commonly associated with one name: Joseph Goldberger of the US Public Health Service, who in 1914 went south, concluded within 4 months that the cause was inadequate diet, spent the rest of his life researching the disease, and—before his death from cancer in 1929—found that brewer's yeast could prevent and treat it at nominal cost. It does Goldberger no discredit to emphasize that between 1907 and 1914 a patchwork coalition of asylum superintendents, practicing physicians, local health officials, and others established for the first time an English-language competence in pellagra, sifted through competing hypotheses, and narrowed the choices down to two: an insect-borne infection hypothesis, championed by the flamboyant European Louis Westerna Sambon, and the new “vitamine hypothesis,” proffered by Casimir Funk in early 1912 and articulated later that year by two members of the American Clinical and Climatological Association, Fleming Mant Sandwith and Rupert Blue. Those who resisted Goldberger's inconvenient truth that the root cause was southern poverty drew their arguments largely from the Thompson-McFadden Pellagra Commission, which traces back to Sambon's unfortunate influence on American researchers. Thousands died as a result. PMID:26330657

  12. Pellagra Pre-Goldberger: Rupert Blue, Fleming Sandwith, and The "Vitamine Hypothesis".

    PubMed

    Bryan, Charles S; Mull, Shane R

    2015-01-01

    The conquest of pellagra is commonly associated with one name: Joseph Goldberger of the US Public Health Service, who in 1914 went south, concluded within 4 months that the cause was inadequate diet, spent the rest of his life researching the disease, and--before his death from cancer in 1929--found that brewer's yeast could prevent and treat it at nominal cost. It does Goldberger no discredit to emphasize that between 1907 and 1914 a patchwork coalition of asylum superintendents, practicing physicians, local health officials, and others established for the first time an English-language competence in pellagra, sifted through competing hypotheses, and narrowed the choices down to two: an insect-borne infection hypothesis, championed by the flamboyant European Louis Westerna Sambon, and the new "vitamine hypothesis," proffered by Casimir Funk in early 1912 and articulated later that year by two members of the American Clinical and Climatological Association, Fleming Mant Sandwith and Rupert Blue. Those who resisted Goldberger's inconvenient truth that the root cause was southern poverty drew their arguments largely from the Thompson-McFadden Pellagra Commission, which traces back to Sambon's unfortunate influence on American researchers. Thousands died as a result. PMID:26330657

  13. Recent Ice Loss from the Fleming and Other Glaciers, Wordie Bay, West Antarctic Peninsula

    NASA Technical Reports Server (NTRS)

    Rignot, E.; Casassa, G.; Gogineni, S.; Kanagaratnam, P.; Krabill, W.; Pritchard, H.; Rivera, A.; Thomas, R.; Turner, J.; Vaughan, D.

    2005-01-01

    Satellite radar interferometry data from 1995 to 2004, and airborne ice thickness data from 2002, reveal that the glaciers flowing into former Wordie Ice Shelf, West Antarctic Peninsula, discharge 6.8 +/- 0.3 km(exp 3)/yr of ice, which is 84 +/- 30 percent larger than a snow accumulation of 3.7 +/- 0.8 km(exp 3)/yr over a 6,300 km(exp 2) drainage basin. Airborne and ICESat laser altimetry elevation data reveal glacier thinning at rates up to 2 m/yr. Fifty km from its ice front, Fleming Glacier flows 50 percent faster than it did in 1974 prior to the main collapse of Wordie Ice Shelf. We conclude that the glaciers accelerated following ice shelf removal, and have been thinning and losing mass to the ocean over the last decade. This and other observations suggest that the mass loss from the northern part of the Peninsula is not negligible at present.

  14. Differential regional expression of multiple ADAMs during feather bud formation.

    PubMed

    Lin, Juntang; Luo, Jiankai; Redies, Christoph

    2011-09-01

    The expression of seven members of the ADAM family was investigated by in situ hybridization in the developing feather buds of chicken. The expression profiles of the ADAMs in the cells and tissues of the feather buds differ from each other. ADAM9, ADAM10, and ADAM17 are expressed in the epidermis of the feather bud, whereas ADAM23 expression is restricted to the bud crest, with a distribution similar to that of sonic hedgehog. ADAM13 is not only expressed in the epidermis, but also in restricted regions of the dermis. Both ADAM12 and ADAM22 are expressed in the dermis of the feather bud, with an opposite mediolateral and anteroposterior polarity. Furthermore, the mRNAs of all investigated ADAMs show regional differences in their expression, for example, in the neck and in the roots of the leg and wing. These results suggest that ADAMs play a variety of roles during avian feather bud formation.

  15. Evaluating the (your country here) olympic medal count.

    PubMed

    Seiler, Stephen

    2013-03-01

    An Olympic Games is a measurable test of a nation´s sporting power. Medal counts are the object of intense scrutiny after every Olympiad. Most countries celebrate any medal with national glee, since 60% of competing countries will win none. In 2012, 10% of the competing countries won 75% of all medals. Despite this concentration among a few countries, more countries are winning more medals now than 20 years ago, thanks in part to athlete-support and -development programs arising around the globe. Small strong sporting countries like Norway are typified by fairly large variation in medal results from Olympiad to Olympiad and a high concentration of results in a few sports. These are important factors to consider when evaluating national performance and interpreting the medal count. Medal conversion, podium placements relative to top 8 placements, may provide a measure of the competitiveness of athlete-support programs in this international zero sum game where the cost of winning Olympic gold keeps rising whether measured in dollars or human capital.  PMID:23428493

  16. Evaluating the (your country here) olympic medal count.

    PubMed

    Seiler, Stephen

    2013-03-01

    An Olympic Games is a measurable test of a nation´s sporting power. Medal counts are the object of intense scrutiny after every Olympiad. Most countries celebrate any medal with national glee, since 60% of competing countries will win none. In 2012, 10% of the competing countries won 75% of all medals. Despite this concentration among a few countries, more countries are winning more medals now than 20 years ago, thanks in part to athlete-support and -development programs arising around the globe. Small strong sporting countries like Norway are typified by fairly large variation in medal results from Olympiad to Olympiad and a high concentration of results in a few sports. These are important factors to consider when evaluating national performance and interpreting the medal count. Medal conversion, podium placements relative to top 8 placements, may provide a measure of the competitiveness of athlete-support programs in this international zero sum game where the cost of winning Olympic gold keeps rising whether measured in dollars or human capital. 

  17. Dahlen Receives 2003 Inge Lehmann Medal

    NASA Astrophysics Data System (ADS)

    Nolet, Guust; Dahlen, Francis A., Jr.

    2004-01-01

    ``I feel honored and pleased to cite my friend and Princeton colleague Tony Dahlen for the Inge Lehmann medal. Given Tony's wide range of important contributions, there is actually a choice of AGU honors one might cite him for; his influence extends well beyond those fields that are primarily associated with the Lehmann Medal. ``Tony started his scientific journey as an undergraduate at Caltech. By the time he moved on to graduate studies with George Backus and Freeman Gilbert at Scripps he was already applying his many talents to geophysics. He soon pioneered a series of papers on normal modes that represent the first substantial step away from Earth's spherical symmetry. In fact, all of the current research on the use of low-frequency seismic data for the determination of the Earth's three-dimensional structure is based on this early work, its extension to an inverse problem, and subsequent research with Martin Smith and John Woodhouse. His interest in the theory of global tomography has survived until this day: Recently he developed a very elegant and efficient theory to include the frequency-dependent effects of diffraction into body wave tomography, a theoretical improvement that was almost immediately rewarded by the imaging of a large number of mantle plumes. These represent the first concrete seismological evidence that many hot spots originate deep in the mantle, confirming Jason Morgan's long-standing hypothesis.

  18. Preliminary hydrogeologic investigation of the Maxey Flats radioactive waste burial site, Fleming County, Kentucky

    USGS Publications Warehouse

    Zehner, Harold H.

    1979-01-01

    Burial trenches at the Maxey Flats radioactive waste burial site , Fleming County, Ky., cover an area of about 0.03 square mile, and are located on a plateau, about 300 to 400 feet above surrounding valleys. Although surface-water characteristics are known, little information is available regarding the ground-water hydrology of the Maxey Flats area. If transport of radionuclides from the burial site were to occur, water would probably be the principal mechanism of transport by natural means. Most base flow in streams around the burial site is from valley alluvium, and from the mantle of regolith, colluvium, and soil partially covering adjacent hills. Very little base flow is due to ground-water flow from bedrock. Most water in springs is from the mantle, rather than from bedrock. Rock units underlying the Maxey Flats area are, in descending order, the Nancy and Farmers Members of the Borden Formation, Sunbury, Bedford, and Ohio Shales, and upper part of the Crab Orchard Formation. These units are mostly shales, except for the Farmers Member, which is mostly sandstone. Total thickness of the rocks is about 320 feet. All radioactive wastes are buried in the Nancy Member. Most ground-water movement in bedrock probably occurs in fractures. The ground-water system at Maxey Flats is probably unconfined, and recharge occurs by (a) infiltration of rainfall into the mantle, and (b) vertical, unsaturated flow from the saturated regolith on hilltops to saturated zones in the Farmers Member and Ohio Shale. Data are insufficient to determine if saturated zones exist in other rock units. The upper part of the Crab Orchard Formation is probably a hydrologic boundary, with little ground-water flow through the formation. (USGS)

  19. Genome sequence of the Fleming strain of Micrococcus luteus, a simple free- living actinobacterium

    SciTech Connect

    Young, Michael; Artsatbanov, Vladislav; Beller, Harry R.; Chandra, Govind; Chater, Keith F.; Dover, Lynn G.; Goh, Ee-Been; Kahan, Tamar; Kaprelyants, Arseny S.; Kyrpides, Nikos; Lapidus, Alla; Lowry, Stephen R.; Lykidis, Athanasios; Mahillon, Jacques; Markowitz, Viktor; Mavrommatis, Konstantinos; Mukamolova, Galina V.; Oren, Aharon; Rokem, J. Stefan; Smith, Margaret C. M.; Young, Danielle I.; Greenblatt, Charles L.

    2009-11-01

    Micrococcus luteus (NCTC2665, Fleming strain) has one of the smallest genomes of free living actinobacteria sequenced to date, comprising a single circular chromosome of 2,501,097 bp (G+C content 73%) predicted to encode 2403 proteins. The genome shows extensive synteny with that of the closely related organism, Kocuria rhizophila, from which it was taxonomically separated relatively recently. Despite its small size, the genome harbors 73 IS elements, almost all of which are closely related to elements found in other actinobacteria. An IS element is inserted into the rrs gene of one of only two rrn operons found in M. luteus. The genome encodes only four sigma factors and fourteen response regulators, indicative of adaptation to a rather strict ecological niche (mammalian skin). The high sensitivity of M. luteus to {Beta}-lactam antibiotics may result from the presence of a reduced set of penicillin binding proteins and the absence of a wblC gene, which plays an important role in antibiotic resistance in other actinobacteria. Consistent with the restricted range of compounds it can use as a sole source of carbon for energy and growth, M. luteus has a minimal complement of genes concerned with carbohydrate transport and metabolism and its inability to utilize glucose as a sole carbon source may be due to the apparent absence of a gene encoding glucokinase. Uniquely among characterized bacteria, M. luteus appears to be able to metabolize glycogen only via trehalose, and to make trehalose only via glycogen. It has very few genes associated with secondary metabolism. In contrast to other actinobacteria, M. luteus encodes only one resuscitation-promoting factor (Rpf) required for emergence from dormancy and its complement of other dormancy-related proteins is also much reduced. M. luteus is capable of long-chain alkene biosynthesis, which is of interest for advanced biofuel production; a three gene cluster essential for this metabolism has been identified in the genome.

  20. Cleavage Site Localization Differentially Controls Interleukin-6 Receptor Proteolysis by ADAM10 and ADAM17

    PubMed Central

    Riethmueller, Steffen; Ehlers, Johanna C.; Lokau, Juliane; Düsterhöft, Stefan; Knittler, Katharina; Dombrowsky, Gregor; Grötzinger, Joachim; Rabe, Björn; Rose-John, Stefan; Garbers, Christoph

    2016-01-01

    Limited proteolysis of the Interleukin-6 Receptor (IL-6R) leads to the release of the IL-6R ectodomain. Binding of the cytokine IL-6 to the soluble IL-6R (sIL-6R) results in an agonistic IL-6/sIL-6R complex, which activates cells via gp130 irrespective of whether the cells express the IL-6R itself. This signaling pathway has been termed trans-signaling and is thought to mainly account for the pro-inflammatory properties of IL-6. A Disintegrin And Metalloprotease 10 (ADAM10) and ADAM17 are the major proteases that cleave the IL-6R. We have previously shown that deletion of a ten amino acid long stretch within the stalk region including the cleavage site prevents ADAM17-mediated cleavage, whereas the receptor retained its full biological activity. In the present study, we show that deletion of a triple serine (3S) motif (Ser-359 to Ser-361) adjacent to the cleavage site is sufficient to prevent IL-6R cleavage by ADAM17, but not ADAM10. We find that the impaired shedding is caused by the reduced distance between the cleavage site and the plasma membrane. Positioning of the cleavage site in greater distance towards the plasma membrane abrogates ADAM17-mediated shedding and reveals a novel cleavage site of ADAM10. Our findings underline functional differences in IL-6R proteolysis by ADAM10 and ADAM17. PMID:27151651

  1. Interview With the 2002 Caldecott Medal Winner, David Wiesner.

    ERIC Educational Resources Information Center

    Giorgis, Cyndi; Johnson, Nancy J.

    2003-01-01

    Discusses David Wiesner, the 2002 Caldecott Medal Winner, and includes excerpts of an interview with him. Notes that Wiesner's books appeal to the imagination and often use art elements such as scale. Details the winning book, "The Three Pigs." (PM)

  2. Raymond G. Roble Receives 2013 William Bowie Medal: Response

    NASA Astrophysics Data System (ADS)

    Roble, Raymond G.

    2014-01-01

    It is a great honor to receive the 2013 Bowie Medal knowing that it comes from such a prestigious and renowned geophysical society and from AGU colleagues whom I have interacted with for the past 45 years.

  3. In Brief: Nominations requested for U.S. science medals

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2011-02-01

    Scientists can help recognize the contributions of colleagues by submitting nominations for the National Medal of Science and the National Medal of Technology and Innovation, which are the highest honors the president bestows in science, technology, and innovation. The National Medal of Science, the nation's highest honor for American scientists and engineers, is given to individuals deserving special recognition for outstanding contributions to knowledge, or the total impact of their work, in the chemical, physical, biological, mathematical, engineering, or behavioral sciences. Nominations and three letters of support must be submitted by 31 March. For more information, contact program manager Mayra Montrose at nms@nsf.gov or +1-703-292-8040, or visit http://www.nsf.gov/od/nms/medal.jsp.

  4. John Quincy Adams's rhetorical crusade for astronomy.

    PubMed

    Portolano, M

    2000-09-01

    Astronomy thrived in Europe during the early nineteenth century, but in the United States a utilitarian mind-set opposed it. John Quincy Adams's oratory in support of American astronomical discovery reached its peak during congressional debate over the Smithsonian Institution (1838-1846). During this debate Adams countered proposals to found a university with plans for an observatory. His addresses to congressional and public audiences about observatories and astronomy were intended to foster interest in the science and encourage the growing astronomical community in America. Although the U.S. Naval Observatory in Washington, D.C., was established before the Smithsonian debate ended, many considered Adams its political father. Adams composed his speeches on astronomy in a systematic manner, following neoclassical principles of rhetoric that he had taught at Harvard University. His speeches both in and outside of Congress show evidence of the rhetorical principles he conscientiously used in the service of astronomy.

  5. John Quincy Adams's rhetorical crusade for astronomy.

    PubMed

    Portolano, M

    2000-09-01

    Astronomy thrived in Europe during the early nineteenth century, but in the United States a utilitarian mind-set opposed it. John Quincy Adams's oratory in support of American astronomical discovery reached its peak during congressional debate over the Smithsonian Institution (1838-1846). During this debate Adams countered proposals to found a university with plans for an observatory. His addresses to congressional and public audiences about observatories and astronomy were intended to foster interest in the science and encourage the growing astronomical community in America. Although the U.S. Naval Observatory in Washington, D.C., was established before the Smithsonian debate ended, many considered Adams its political father. Adams composed his speeches on astronomy in a systematic manner, following neoclassical principles of rhetoric that he had taught at Harvard University. His speeches both in and outside of Congress show evidence of the rhetorical principles he conscientiously used in the service of astronomy. PMID:11143785

  6. ADAM: All-Data Asteroid Modeling

    NASA Astrophysics Data System (ADS)

    Viikinkoski, Matti; Kaasalainen, Mikko; Durech, Josef

    2015-02-01

    ADAM (All-Data Asteroid Modeling) models asteroid shape reconstruction from observations. Developed in MATLAB with core routines in C, its features include general nonconvex and non-starlike parametric 3D shape supports and reconstruction of asteroid shape from any combination of lightcurves, adaptive optics images, HST/FGS data, disk-resolved thermal images, interferometry, and range-Doppler radar images. ADAM does not require boundary contour extraction for reconstruction and can be run in parallel.

  7. In Brief: National Medal of Science nomination deadline

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2010-03-01

    The deadline for nominations for the 2010 U.S. National Medal of Science is 31 March 2010. The Medal of Science, which is presented annually by the president of the United States to distinguished scientists and engineers, is the nation's highest honor for American scientists and engineers. For more information, visit http://www.nsf.gov/od/nms/nominations.jsp or contact Mayra Montrose at the U.S. National Science Foundation, mmontros@nsf.gov.

  8. PROTEOLYTIC PROCESSING OF DELTA-LIKE 1 BY ADAM PROTEASES*

    PubMed Central

    Dyczynska, Emilia; Sun, Danqiong; Yi, Haiqing; Sehara-Fujisawa, Atsuko; Blobel, Carl P.; Zolkiewska, Anna

    2009-01-01

    Delta-like 1 (Dll1) is a mammalian ligand for Notch receptors. Interactions between Dll1 and Notch in trans activate the Notch pathway, whereas Dll1 binding to Notch in cis inhibits Notch signaling. Dll1 undergoes proteolytic processing in its extracellular domain by ADAM10. In this work, we demonstrate that Dll1 represents a substrate for several other members of the ADAM family. In co-transfected cells, Dll1 is constitutively cleaved by ADAM12, and the N-terminal fragment of Dll1 is released to medium. ADAM12-mediated cleavage of Dll1 is cell density-dependent, takes place in cis orientation, and does not require the presence of the cytoplasmic domain of ADAM12. Full length Dll1, but not its N- or C-terminal proteolytic fragment, co-immunoprecipitates with ADAM12. By using a Notch reporter construct, we show that Dll1 processing by ADAM12 increases Notch signaling in a cell-autonomous manner. Furthermore, ADAM9 and ADAM17 have the ability to process Dll1. In contrast, ADAM15 does not cleave Dll1, although the two proteins still co-immunoprecipitate with each other. Asn353 present in the catalytic motif of ADAM12 and other Dll1-processing ADAMs, but absent in ADAM15, is necessary for Dll1 cleavage. Dll1 cleavage is reduced in ADAM9/12/15−/− mouse embryonic fibroblasts (MEFs), suggesting that the endogenous ADAM9 and/or ADAM12 present in wild type MEFs contribute to Dll1 processing. Finally, the endogenous Dll1 present in primary mouse myoblasts undergoes cleavage in confluent, differentiating myoblast cultures and this cleavage is decreased by ADAM12 siRNAs. Our findings expand the role of ADAM proteins in the regulation of Notch signaling. PMID:17107962

  9. 75 FR 8043 - National Medal of Technology and Innovation Nomination Evaluation Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-23

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Nomination... requesting nominations of individuals to serve on the National Medal of Technology and Innovation Nomination..., National Medal of Technology and Innovation Program, United States Patent and Trademark Office, P.O....

  10. 75 FR 3203 - National Medal of Technology and Innovation Call for 2010 Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-20

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Call for 2010... nominations for its National Medal of Technology and Innovation (NMTI). Since establishment by Congress in 1980, the President of the United States has awarded the National Medal of Technology and...

  11. 76 FR 80901 - National Medal of Technology and Innovation Nomination Evaluation Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Nomination... requesting nominations of individuals to serve on the National Medal of Technology and Innovation Nomination...: Nominations must be submitted to: Program Manager, National Medal of Technology and Innovation Program,...

  12. 76 FR 76388 - National Medal of Technology and Innovation Nomination Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-07

    ... Patent and Trademark Office National Medal of Technology and Innovation Nomination Application ACTION....'' SUPPLEMENTARY INFORMATION: I. Abstract The National Medal of Technology and Innovation is the highest honor for... innovation, and development of the Nation's technological manpower. The purpose of the National Medal...

  13. 78 FR 35604 - National Medal of Technology and Innovation Nomination Evaluation Committee Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Nomination... closed meeting. SUMMARY: The National Medal of Technology and Innovation (NMTI) Nomination Evaluation..., National Medal of Technology and Innovation Program, United States Patent and Trademark Office, P.O....

  14. 31 CFR 92.2 - Sale of “list” medals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Sale of âlistâ medals. 92.2 Section 92.2 Money and Finance: Treasury Regulations Relating to Money and Finance UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.2 Sale of “list” medals. Medals on the regular Mint...

  15. 77 FR 51826 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Bureau.... SUMMARY: This is an announcement of a meeting of the Public Safety Officer Medal of Valor Review Board to review and vote on recommendations for the 2011-2012 Medal of Valor nominations, consider issues...

  16. 75 FR 54915 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Office... meeting/conference call of the Public Safety Officer Medal of Valor Review Board to vote on recommendations for the 2009-2010 Medal of Valor nominations, review issues relevant to the nomination...

  17. 76 FR 37375 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-27

    ... of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Office...: This is an announcement of a meeting via conference call of the Public Safety Officer Medal of Valor... Medal of Valor Review Board carries out those advisory functions specified in 42 U.S.C. 15202....

  18. 76 FR 56226 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ... of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Office... meeting via conference call of the Public Safety Officer Medal of Valor Review Board to vote of the... Public Safety Officer Medal of Valor Review Board carries out those advisory functions specified in 42...

  19. 75 FR 30859 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Office... meeting via conference call of the Public Safety Officer Medal of Valor Review Board to vote on the... . ] SUPPLEMENTARY INFORMATION: The Public Safety Officer Medal of Valor Review Board carries out those...

  20. 78 FR 43227 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ... of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Office.... SUMMARY: This is an announcement of a meeting of the Public Safety Officer Medal of Valor Review Board to review and vote on recommendations for the 2012-2013 Medal of Valor nominations, consider issues...

  1. 33 CFR 13.01-25 - Description of Gold Lifesaving Medal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Description of Gold Lifesaving Medal. 13.01-25 Section 13.01-25 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals,...

  2. 33 CFR 13.01-25 - Description of Gold Lifesaving Medal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Description of Gold Lifesaving Medal. 13.01-25 Section 13.01-25 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals,...

  3. 33 CFR 13.01-30 - Description of Silver Lifesaving Medal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Description of Silver Lifesaving Medal. 13.01-30 Section 13.01-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals,...

  4. 33 CFR 13.01-30 - Description of Silver Lifesaving Medal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Description of Silver Lifesaving Medal. 13.01-30 Section 13.01-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals,...

  5. 33 CFR 13.01-30 - Description of Silver Lifesaving Medal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Description of Silver Lifesaving Medal. 13.01-30 Section 13.01-30 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY GENERAL DECORATIONS, MEDALS, RIBBONS AND SIMILAR DEVICES Gold and Silver Lifesaving Medals,...

  6. Epithelial cell ADAM17 activation by Helicobacter pylori: role of ADAM17 C-terminus and Threonine-735 phosphorylation.

    PubMed

    McClurg, Urszula L; Danjo, Kazuma; King, Harry O; Scott, Gina B; Robinson, Philip A; Crabtree, Jean E

    2015-03-01

    Helicobacter pylori transactivates the epidermal growth factor receptor (EGFR) on gastric epithelial cells via a signalling cascade involving a disintegrin and metalloprotease 17 (ADAM17) cleavage of membrane bound heparin binding-epidermal growth factor (HB-EGF). The effects of H. pylori on ADAM17 C-terminus in epithelial cells have been examined. Total cellular ADAM17 and surface expression of ADAM17 were significantly increased by H. pylori in AGS gastric epithelial cells. These changes were associated with ADAM17 C-terminal phosphorylation at T375 and S791. AGS cells lacking the ADAM17 C-terminal domain induced significantly attenuated cleavage of HB-EGF and were also unable to upregulate HB-EGF and EGFR transcripts to the same extent as cells expressing full length ADAM17. In mitotic unstimulated AGS and ADAM17 over-expressing AGS cells, ADAM17 was highly T735 phosphorylated indicating ADAM17 T735 phosphorylation is modified during the cell cycle. In conclusion, H. pylori induced ADAM17 C-terminal T735 and/or S791 phosphorylation in gastric epithelial cells are likely to be an important trigger inducing ADAM17 activation and shedding of HB-EGF leading to EGFR transactivation. ADAM17 over-expression in gastric cancer represents a potential target for therapeutic intervention.

  7. Women in History--Abigail Adams: Life, Accomplishments, and Ideas

    ERIC Educational Resources Information Center

    Kenan, Sharon K.

    2008-01-01

    This article profiles the life, accomplishments, and ideas of Abigail Adams. Born in 1944, Adams lacked a formal education, but she more than made up for that shortcoming with her love of reading, especially literature, and her interests in politics and events surrounding the young colonies. Adams was supportive of the advancement of women. She…

  8. On ``Carrington, Schwabe, and the Gold Medal''

    NASA Astrophysics Data System (ADS)

    Schröder, Wilfried

    2006-06-01

    I note with interest the article by Cliver [2005] about the early solar investigations of Heinrich Schwabe and Richard Carrington and offer some further insights into Schwabe's work and its reception at the time. Schwabe commenced his observations in 1826 with a small telescope he had bought some years earlier. For more than 40 years, he observed the Sun and made meteorological notes. In his 1843 essay, he noted a sunspot cycle of about 10 years, but his result aroused little interest with contemporary astronomers. Research at the time was focused on the physics of the planets, the Moon, and other topics. Schwabe had published data in the well-known Astronomische Nachrichten, but not until Alexander von Humboldt republished it in his Kosmos, volume 3 (1851), did the data begin to be recognized and accepted by Schwabe's fellow scientists. Humboldt's Kosmos was a publication of considerable prestige, and it had a wide circulation among scientists and the educated public. Scwabe's work became familiar to other scientists including Carrington, Angelo Secchi, and Gustav Spörer and, as noted by Cliver, earned him the gold medal of the Royal Astronomical Society.

  9. Paraprofessional of the Year 2009: Tina Adams

    ERIC Educational Resources Information Center

    Berry, John N., III

    2009-01-01

    There is no doubt among the staff and managers at North Carolina State University (NCSU) Libraries, Raleigh, that advanced library technician Tina Adams deserves to be the winner of the "Library Journal's "Paraprofessional of the Year Award for 2009." "Certainly this library has never seen anyone like her before, not in my nine years on staff,"…

  10. Adam Smith and the Rhetoric of Style.

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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)

  12. In Brief: Rita Colwell receives National Medal of Science

    NASA Astrophysics Data System (ADS)

    Kumar, Mohi

    2007-07-01

    Rita Colwell, director of the U.S. National Science Foundation from 1998 to 2004, was awarded a U.S. National Medal of Science in a White House ceremony on 27 July 2007. Colwell, currently a professor of microbiology and biotechnology at the University of Maryland at College Park and a professor at Johns Hopkins University Bloomberg School of Public Health, received the award for her research on global infectious diseases and marine microbes, specifically the bacterium that causes pandemic cholera. The National Medal of Science is the United States' highest honor for scientific achievement. Colwell currently serves on AGU's development board.

  13. ADAM "sequence" part II: hypothesis and speculation.

    PubMed

    Opitz, John M; Johnson, Dennis R; Gilbert-Barness, Enid F

    2015-03-01

    Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito. In 1930 Streeter stated " apodictically" that no evidence has been found that intra-uterine amputation is due to amniotic bands or adhesions …" and that his 16 cases provided (histological) evidence for a "germinal origin." He concluded that an amniotic cord was "not an adhesion or inflammatory product but … an anomalous developmental structure and present from the outset." In survivors the "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958, Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions … are always produced by … the fetus – as a result of dysplasia in foetal tissues. They are the result, not the cause, of foetal malformations." Streeter [1930] mentions a potential familial case (56-year-old man and his mother), not controlled by photographs or other records and concluded "that the (ADAM) deformity is not easily transmissible," but "due to the constitution of the germ-plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that "… proof of amnion rupture without damage to the chorionic sac is no longer "in question." Considering Torpin's decades-long study of the ADAM phenomenon and review of 494 references (missing many) it is surprising that he does not discuss the relationship between the apparent ADAM defects and other, internal anomalies that maybe present in an affected fetus or infant not evidently caused by the amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our review of these internal and other presumed primary malformations in ADAM is ongoing. However, on a preliminary basis, it seems likely to us that: (1) there is an increased

  14. ADAM "sequence" part II: hypothesis and speculation.

    PubMed

    Opitz, John M; Johnson, Dennis R; Gilbert-Barness, Enid F

    2015-03-01

    Noted for centuries in humans, a relatively hairless mammal [e.g., Hallero, 1766; Hohl, 1828 in Klunker, 2003], the so-called amniotic deformities, adhesions, mutilations (ADAM) sequence remains causally and pathogenetically incognito. In 1930 Streeter stated " apodictically" that no evidence has been found that intra-uterine amputation is due to amniotic bands or adhesions …" and that his 16 cases provided (histological) evidence for a "germinal origin." He concluded that an amniotic cord was "not an adhesion or inflammatory product but … an anomalous developmental structure and present from the outset." In survivors the "traces" of damaged limb-buds "reveal the scars of poor germ-plasm." In 1958, Willis, in dismissing the amniotic origin of the ADAM defects (or "Streeter" or "Simonart" bands) quoted Keith [1940] to the effect that "(a)mniotic adhesions … are always produced by … the fetus – as a result of dysplasia in foetal tissues. They are the result, not the cause, of foetal malformations." Streeter [1930] mentions a potential familial case (56-year-old man and his mother), not controlled by photographs or other records and concluded "that the (ADAM) deformity is not easily transmissible," but "due to the constitution of the germ-plasm." Torpin [1968] concluded, as apodictically as Streeter and Willis, that "… proof of amnion rupture without damage to the chorionic sac is no longer "in question." Considering Torpin's decades-long study of the ADAM phenomenon and review of 494 references (missing many) it is surprising that he does not discuss the relationship between the apparent ADAM defects and other, internal anomalies that maybe present in an affected fetus or infant not evidently caused by the amniotic disruptions, adhesions or mutilations, unless his mind was made up. Our review of these internal and other presumed primary malformations in ADAM is ongoing. However, on a preliminary basis, it seems likely to us that: (1) there is an increased

  15. Illnesses of the brain in John Quincy Adams.

    PubMed

    Paulson, George

    2004-12-01

    John Quincy Adams, the sixth and perhaps most scholarly American president, served courageously despite familial essential tremor, depression, and cerebrovascular disease. His cousin Samuel Adams and his father John Adams also had essential tremor, which the later called "quiveration". Alcoholism and depression affected several members of J.Q. Adams's family. Following his own time as president, J.Q. Adams returned to duty as the congressman who most assiduously fought slavery, a fight he continued even after he had suffered a major left hemispheric stroke. His fatal collapse in Congress, protesting the Mexican War, is legendary among the final illnesses of American statesmen. PMID:15545105

  16. Illnesses of the brain in John Quincy Adams.

    PubMed

    Paulson, George

    2004-12-01

    John Quincy Adams, the sixth and perhaps most scholarly American president, served courageously despite familial essential tremor, depression, and cerebrovascular disease. His cousin Samuel Adams and his father John Adams also had essential tremor, which the later called "quiveration". Alcoholism and depression affected several members of J.Q. Adams's family. Following his own time as president, J.Q. Adams returned to duty as the congressman who most assiduously fought slavery, a fight he continued even after he had suffered a major left hemispheric stroke. His fatal collapse in Congress, protesting the Mexican War, is legendary among the final illnesses of American statesmen.

  17. 28 CFR 50.22 - Young American Medals Program.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... worthy of public report. The outstanding and unusual recognition of the candidate's character and service... a candidate eligible, or of adding to a candidate's qualifications, for the award of the Young... either medal in any year will not affect a candidate's eligibility for the award of either or both of...

  18. 28 CFR 50.22 - Young American Medals Program.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... worthy of public report. The outstanding and unusual recognition of the candidate's character and service... a candidate eligible, or of adding to a candidate's qualifications, for the award of the Young... either medal in any year will not affect a candidate's eligibility for the award of either or both of...

  19. 28 CFR 50.22 - Young American Medals Program.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... worthy of public report. The outstanding and unusual recognition of the candidate's character and service... a candidate eligible, or of adding to a candidate's qualifications, for the award of the Young... either medal in any year will not affect a candidate's eligibility for the award of either or both of...

  20. 28 CFR 50.22 - Young American Medals Program.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... worthy of public report. The outstanding and unusual recognition of the candidate's character and service... a candidate eligible, or of adding to a candidate's qualifications, for the award of the Young... either medal in any year will not affect a candidate's eligibility for the award of either or both of...

  1. 38 CFR 3.802 - Medal of Honor.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... certificate issued in which the right of the person named in the certificate to the special pension is set... have received during the period beginning the first day of the month after the date of the event for... payment using the monthly Medal of Honor pension rates in effect from the first day of the month after...

  2. U.S. Students Win Medals in International Chemistry Olympiad.

    ERIC Educational Resources Information Center

    Rawls, Rebecca

    1985-01-01

    The four members of the American team in the International Chemistry Olympiad won medals in this international competition (which involved written/laboratory examinations in organic, inorganic, and physical chemistry, and biochemistry). Selection of the team involved a nationwide examination and participation in a two-week chemistry camp. (DH)

  3. Dr. Shawn Mehlenbacher 2012 Wilder Silver Medal Recipient

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dr. Shawn Mehlenbacher, Oregon State University, was awarded the 2012 Wilder Medal by the American Pomological Society for his contributions to hazelnut genetics and cultivar development. Dr. Mehlenbacher took over the leadership of the Oregon State University hazelnut breeding program in 1986 aft...

  4. 33 CFR 1.26-5 - Replacement of medals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... 937; 14 U.S.C. 501, 633; 49 U.S.C. 1655(b)(1); 49 CFR 1.46(b)) ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Replacement of medals. 1.26-5 Section 1.26-5 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY...

  5. 2000 Newbery Medal Winner: A Conversation with Christopher Paul Curtis.

    ERIC Educational Resources Information Center

    Johnson, Nancy J.; Giorgis, Cyndi

    2001-01-01

    Presents an interview with 2000 Newbery Medal winner Christopher Paul Curtis. Reveals the author's journey as a reader and a writer, offers glimpses into the humor and upbeat attitude of Bud (the main character in Curtis' s award-winning book "Bud, Not Buddy"), and gives a peek into what readers can expect next from this award-winning author. (SR)

  6. 28 CFR 50.22 - Young American Medals Program.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... United States (including its territories and possessions), but need not be a citizen thereof. (ii) These... society. (3) No more than two such medals may be awarded in any one calendar year. (c) Young American... religious institution, group, or society. (3) The recognition of the character and service upon which...

  7. The Gold Medal Fitness Program: A Model for Teacher Change

    ERIC Educational Resources Information Center

    Wright, Jan; Konza, Deslea; Hearne, Doug; Okely, Tony

    2008-01-01

    Background: Following the 2000 Sydney Olympics, the NSW Premier, Mr Bob Carr, launched a school-based initiative in NSW government primary schools called the "Gold Medal Fitness Program" to encourage children to be fitter and more active. The Program was introduced into schools through a model of professional development, "Quality Teaching and…

  8. Non-MacAdam color discrimination ellipses

    NASA Astrophysics Data System (ADS)

    Goldstein, Peter

    2012-10-01

    MacAdam ellipses and the 1976 u'v' chromaticity space are commonly used in the illumination and LED industries. Delta E 2000 (ΔE) is the most up-to-date color difference metric endorsed by CIE and is more reliable than earlier metrics. This paper shows how the ΔE 2000 standard can be used to derive ellipses to be plotted in the well-known 1931 xy color space and examines the validity of MacAdam ellipses and the 1976 u'v' chromaticity space in terms of this metric. The 1976 u'v' chromaticity space is found, in quantitative terms, to be less uniform than the 1931 xy chromaticity space based on ΔE 2000. This paper recommends ΔE calculations as a quantitative tool, the proposed ellipses as a descriptive tool, and the total abandonment of the 1976 u'v' color space.

  9. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

    NASA Astrophysics Data System (ADS)

    Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.

    2015-10-01

    Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling.

  10. The dental health of President John Adams.

    PubMed

    Ring, Malvin E

    2004-01-01

    The oral health of George Washington has been widely studied and written about. Not so, however, with our second president, John Adams, whose dental health was apparently poor throughout his life. His pernicious habit of inducing vomiting to treat various bodily ills, coupled with a great love of sweets, led to the loss of his teeth, which he stubbornly refused to replace with dentures. When he was older, this led to his speech being so badly affected, that he could barely be understood.

  11. Shedding of collagen XVII/BP180 in skin depends on both ADAM10 and ADAM9.

    PubMed

    Franzke, Claus-Werner; Bruckner-Tuderman, Leena; Blobel, Carl P

    2009-08-28

    Collagen XVII is a transmembrane collagen and the major autoantigen of the autoimmune skin blistering disease bullous pemphigoid. Collagen XVII is proteolytically released from the membrane, and the pathogenic epitope harbors the cleavage site for its ectodomain shedding, suggesting that proteolysis has an important role in regulating the function of collagen XVII in skin homeostasis. Previous studies identified ADAMs 9, 10, and 17 as candidate collagen XVII sheddases and suggested that ADAM17 is a major sheddase. Here we show that ADAM17 only indirectly affects collagen XVII shedding and that ADAMs 9 and 10 are the most prominent collagen XVII sheddases in primary keratinocytes because (a) collagen XVII shedding was not stimulated by phorbol esters, known activators of ADAM17, (b) constitutive and calcium influx-stimulated shedding was sensitive to the ADAM10-selective inhibitor GI254023X and was strongly reduced in Adam10(-/-) cells, (c) there was a 55% decrease in constitutive collagen XVII ectodomain shedding from Adam9(-/-) keratinocytes, and (d) H(2)O(2) enhanced ADAM9 expression and stimulated collagen XVII shedding in skin and keratinocytes of wild type mice but not of Adam9(-/-) mice. We conclude that ADAM9 and ADAM10 can both contribute to collagen XVII shedding in skin with an enhanced relative contribution of ADAM9 in the presence of reactive oxygen species. These results provide critical new insights into the identity and regulation of the major sheddases for collagen XVII in keratinocytes and skin and have implications for the treatment of blistering diseases of the skin.

  12. Our Magnetic Planet (Arthur Holmes Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Laj, Carlo

    2015-04-01

    It is a great honour to receive the Arthur Holmes Medal, certainly the highest scientific award of my life. My first thoughts and deep gratitude are with the people who have contributed to me being here today, from my PhD mentors, Pierre Berge and Pierre Pério, later Jacques Labeyrie, my colleagues and students and last, but not least, the members of the Committee on Education of EGU, with whom I have shared over 10 years of a wonderful educational activity. In this presentation, among the various scientific arguments in which I have been involved, I will recall only those mentioned in my letter of nomination to the Holmes Medal, trying to replace them in what was known at the time. After a PhD in Solid State Physics, working in a laboratory of the Commissariat à l'Énergie Atomique, I obtained a post doctoral research position for the the study of liquid binary critical fluids, and worked on this topics for 5 years. I then joined the Centre des Faibles Radioactivités, a CNRS-CEA Institute dedicated to the study of geological-environmental phenomena. My first task there has been to develop a paleomagnetic laboratory, dedicated to the study of Earth Sciences, through the study of the magnetic properties of sediments and igneous rocks. From there on, my entire scientific activity has been devoted to the study of our "Magnetic Planet". My first project in Geophysics dealt with the geodynamical evolution of the Aegean Arc. At the time, only a few paleomagnetic studies existed in the Mediterranean realm, and none in the Aegean region. Moreover all of them dealt with rather old geological formations, so that almost nothing was known about the recent post-cretaceous evolution. The originality of our study was to start from the most recent to the older formations, in order to precisely describe "retro-tectonically" the different phases of rotational deformation. This intensive study (over 700 sampling sites, over 10,000 samples spread over continental Greece, the Aegean

  13. Our Magnetic Planet (Arthur Holmes Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Laj, Carlo

    2015-04-01

    It is a great honour to receive the Arthur Holmes Medal, certainly the highest scientific award of my life. My first thoughts and deep gratitude are with the people who have contributed to me being here today, from my PhD mentors, Pierre Berge and Pierre Pério, later Jacques Labeyrie, my colleagues and students and last, but not least, the members of the Committee on Education of EGU, with whom I have shared over 10 years of a wonderful educational activity. In this presentation, among the various scientific arguments in which I have been involved, I will recall only those mentioned in my letter of nomination to the Holmes Medal, trying to replace them in what was known at the time. After a PhD in Solid State Physics, working in a laboratory of the Commissariat à l'Énergie Atomique, I obtained a post doctoral research position for the the study of liquid binary critical fluids, and worked on this topics for 5 years. I then joined the Centre des Faibles Radioactivités, a CNRS-CEA Institute dedicated to the study of geological-environmental phenomena. My first task there has been to develop a paleomagnetic laboratory, dedicated to the study of Earth Sciences, through the study of the magnetic properties of sediments and igneous rocks. From there on, my entire scientific activity has been devoted to the study of our "Magnetic Planet". My first project in Geophysics dealt with the geodynamical evolution of the Aegean Arc. At the time, only a few paleomagnetic studies existed in the Mediterranean realm, and none in the Aegean region. Moreover all of them dealt with rather old geological formations, so that almost nothing was known about the recent post-cretaceous evolution. The originality of our study was to start from the most recent to the older formations, in order to precisely describe "retro-tectonically" the different phases of rotational deformation. This intensive study (over 700 sampling sites, over 10,000 samples spread over continental Greece, the Aegean

  14. The good, the bad and the ugly substrates for ADAM10 and ADAM17 in brain pathology, inflammation and cancer.

    PubMed

    Pruessmeyer, Jessica; Ludwig, Andreas

    2009-04-01

    Various surface molecules undergo regulated cleavage by the disintegrin and metalloproteinases ADAM10 and ADAM17. The list of substrates includes molecules involved in brain pathology, inflammation and cancer. In the brain both proteases mediate neuroprotective cleavage events such as inactivation of amyloid precursor protein. In inflammatory settings signaling of cytokines including TNFalpha and IL-6 is triggered by proteolytic release of soluble agonists and leukocyte recruitment is controlled by the cleavage of adhesion molecules. Moreover, in tumors, ADAM10- and ADAM17-mediated shedding events trigger proliferative signaling via activation of growth factors including ErbB family members. Concepts of either increasing ADAM10- or ADAM17-activity to limit neurodegeneration or suppressing their activity to block inflammation or tumor growth have to be carefully scrutinized for their potential side effects in various tissues and pathologies. PMID:18951988

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

    ERIC Educational Resources Information Center

    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…

  16. John Tyndall and the Royal Medal that was never struck

    PubMed Central

    Jackson, Roland

    2014-01-01

    Just once in its long history has a Royal Medal been awarded but not presented. John Tyndall FRS (1820–93) was the chosen recipient in 1853 for his early work on diamagnetism but declined to accept it. The story of why Tyndall felt compelled to turn down this considerable honour sheds light on the scientific politics and personal relationships of the time, on the importance given to the study of magnetism, and on Tyndall's own character and career. PMID:24921107

  17. Connective tissue growth factor is a substrate of ADAM28

    SciTech Connect

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

    2010-11-26

    Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 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{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 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{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.

  18. ADAM12 and ADAM17 gene expression in laser-capture microdissected and non-microdissected breast tumors.

    PubMed

    Narita, Diana; Seclaman, Edward; Ilina, Razvan; Cireap, Natalia; Ursoniu, Sorin; Anghel, Andrei

    2011-06-01

    ADAM (a disintegrin and metalloprotease)12 and ADAM17 are multidomain transmembrane proteins involved in ectodomain shedding of cytokines, growth factors and adhesion molecules, with pivotal activities in the tumor microenvironment. The aim of this study was to confirm the up-regulation of ADAM17 and ADAM12 gene splicing variants in breast tumors and to delineate their expression between laser-capture microdissected (LCM) and non-microdissected breast tumors. The gene expression was analyzed by quantitative-reverse transcription-PCR in a total sample of 109 breast tumors paired with corresponding non-neoplastic breast tissues. ADAM12 and 17 proteins expression for corresponding tissue samples was confirmed by immunohistochemistry. ADAM12S, 12L and 17 genes were significantly up-regulated in either malign or benign LCM samples when compared to non-tumor controls. For non-LCM samples, it was obtained also an increased expression for ADAM12 and 17 genes in cancers, while in benign tumors only ADAM12 variants were significantly up-regulated compared to controls. When benign versus malignant tumors were compared, in LCM samples all investigated genes displayed a higher expression in cancers, whereas in non-LCM, ADAM12 variants were overexpressed in benign samples. The increased expression of ADAM12 protein in the tumor cells and stroma of benign breast diseases was immunohistochemically confirmed. These differences between LCM and non-LCM samples were explained by the contribution of the stroma to the expression of this marker. This study underlines the accuracy conferred by homogenous LCM samples on gene expression profiles and confers further evidence regarding the role of ADAM12 and 17 in the breast tumorigenesis and progression.

  19. ADAM8 as a drug target in Pancreatic Cancer

    PubMed Central

    Schlomann, Uwe; Koller, Garrit; Conrad, Catharina; Ferdous, Taheera; Golfi, Panagiota; Garcia, Adolfo Molejon; Höfling, Sabrina; Parsons, Maddy; Costa, Patricia; Soper, Robin; Bossard, Maud; Hagemann, Thorsten; Roshani, Rozita; Sewald, Norbert; Ketchem, Randal R.; Moss, Marcia L.; Rasmussen, Fred H.; Miller, Miles A.; Lauffenburger, Douglas A.; Tuveson, David A.; Nimsky, Christopher; Bartsch, Jörg W.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a grim prognosis with less than 5% survivors after 5 years. High expression levels of ADAM8, a metalloprotease-disintegrin, are correlated with poor clinical outcome. We show that ADAM8 expression is associated with increased migration and invasiveness of PDAC cells caused by activation of ERK 1/2 and higher MMP activities. For biological function, ADAM8 requires multimerisation and associates with β1-integrin on the cell surface. A peptidomimetic ADAM8 inhibitor, BK-1361, designed by structural modelling of the disintegrin domain, prevents ADAM8 multimerisation. In PDAC cells, BK-1361 affects ADAM8 function leading to reduced invasiveness, and less ERK 1/2 and MMP activation. BK-1361 application in mice decreased tumour burden and metastasis of implanted pancreatic tumour cells and provides improved metrics of clinical symptoms and survival in a KrasG12D-driven mouse model of PDAC. Thus, our data integrate ADAM8 in pancreatic cancer signalling and validate ADAM8 as a target for PDAC therapy. PMID:25629724

  20. "Adam of the Road" by Elizabeth Janet Gray. Literature Unit.

    ERIC Educational Resources Information Center

    Robbins, Mari Lu

    Intended as an aid to classroom teachers, this 48-page handbook presents a literature unit based on the children's book, "Adam of the Road" by Elizabeth Janet Gray. It begins with sample lesson plans, pre-reading activities, author information, a book summary, and vocabulary lists and suggested vocabulary activities. Next, chapters of "Adam of the…

  1. ADAM8 as a drug target in pancreatic cancer.

    PubMed

    Schlomann, Uwe; Koller, Garrit; Conrad, Catharina; Ferdous, Taheera; Golfi, Panagiota; Garcia, Adolfo Molejon; Höfling, Sabrina; Parsons, Maddy; Costa, Patricia; Soper, Robin; Bossard, Maud; Hagemann, Thorsten; Roshani, Rozita; Sewald, Norbert; Ketchem, Randal R; Moss, Marcia L; Rasmussen, Fred H; Miller, Miles A; Lauffenburger, Douglas A; Tuveson, David A; Nimsky, Christopher; Bartsch, Jörg W

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a grim prognosis with <5% survivors after 5 years. High expression levels of ADAM8, a metalloprotease disintegrin, are correlated with poor clinical outcome. We show that ADAM8 expression is associated with increased migration and invasiveness of PDAC cells caused by activation of ERK1/2 and higher MMP activities. For biological function, ADAM8 requires multimerization and associates with β1 integrin on the cell surface. A peptidomimetic ADAM8 inhibitor, BK-1361, designed by structural modelling of the disintegrin domain, prevents ADAM8 multimerization. In PDAC cells, BK-1361 affects ADAM8 function leading to reduced invasiveness, and less ERK1/2 and MMP activation. BK-1361 application in mice decreased tumour burden and metastasis of implanted pancreatic tumour cells and provides improved metrics of clinical symptoms and survival in a Kras(G12D)-driven mouse model of PDAC. Thus, our data integrate ADAM8 in pancreatic cancer signalling and validate ADAM8 as a target for PDAC therapy.

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

    ERIC Educational Resources Information Center

    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)

  3. Character Traits Depicted in Newbery Medal Books from the 1920s through the 2000s

    ERIC Educational Resources Information Center

    Fleming, Kimberly; Parker, Karen

    2013-01-01

    Readers readily identify with characters in literature; therefore, educators must be acutely aware of the overt and underlying messages conveyed in Newbery Medal books. In this quantitative content analysis with a qualitative component, the researchers employed nonparametric measurements to examine Newbery Medal books from the 1920s to the 2000s…

  4. A Guide to Newbery Medal Winners and Honor Books, 1977-1984.

    ERIC Educational Resources Information Center

    Kinman, Judith R.; Henderson, Darwin L.

    Intended for use by teachers, librarians, and parents, this guide analyzes Newbery Award Medal and honor winning books (1977 through 1984) for sexism. Following a statement of criteria, established by the American Library Association concerning the type of book that should receive the medal and honor citations, and the guidelines used to determine…

  5. 77 FR 2047 - National Medal of Technology and Innovation Call for 2012 Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-13

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Call for 2012... nominations for the National Medal of Technology and Innovation (NMTI). Since establishment by Congress in the Stevenson-Wydler Technology Innovation Act of 1980, the President of the United States has awarded...

  6. 78 FR 90 - National Medal of Technology and Innovation Call for 2013 Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-02

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Call for 2013...) is accepting nominations for the National Medal of Technology and Innovation (NMTI). Since establishment by Congress in the Stevenson-Wydler Technology Innovation Act of 1980, the President of the...

  7. 78 FR 78838 - National Medal of Technology and Innovation Call for 2014 Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Call for 2014... nominations for the National Medal of Technology and Innovation (NMTI). Since establishment by Congress in the Stevenson-Wydler Technology Innovation Act of 1980, the President of the United States has awarded...

  8. 75 FR 82378 - National Medal of Technology and Innovation Call for 2011 Nominations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-30

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Call for 2011... nominations for the National Medal of Technology and Innovation (NMTI). Since establishment by Congress in the Stevenson-Wydler Technology Innovation Act of 1980, the President of the United States has awarded...

  9. 31 CFR 92.2 - Sale of “list” medals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.2 Sale of “list” medals. Medals on the regular Mint list, when available, are sold to the public at a charge... available for sale and their selling prices may be obtained from the Director of the Mint, Washington, DC....

  10. 31 CFR 92.2 - Sale of “list” medals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.2 Sale of “list” medals. Medals on the regular Mint list, when available, are sold to the public at a charge... available for sale and their selling prices may be obtained from the Director of the Mint, Washington, DC....

  11. 31 CFR 92.2 - Sale of “list” medals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., DEPARTMENT OF THE TREASURY UNITED STATES MINT OPERATIONS AND PROCEDURES Numismatic Operations § 92.2 Sale of “list” medals. Medals on the regular Mint list, when available, are sold to the public at a charge... available for sale and their selling prices may be obtained from the Director of the Mint, Washington, DC....

  12. Gold Medal Award for Life Achievement in Psychology in the Public Interest.

    PubMed

    2014-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2014 recipient of the Gold Medal Award for Life Achievement in Psychology in the Public Interest is Bonnie R. Strickland.

  13. Gold Medal Award for Life Achievement in the Science of Psychology.

    PubMed

    2014-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2014 recipient of the Gold Medal Award for Life Achievement in the Science of Psychology is Thomas J. Bouchard Jr.

  14. Gold Medal Award for Life Achievement in the Application of Psychology.

    PubMed

    2014-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2014 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology is Richard M. Lerner.

  15. Gold Medal Award for Life Achievement in the Practice of Psychology.

    PubMed

    2014-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2014 recipient of the Gold Medal Award for Life Achievement in the Practice of Psychology is Gilbert O. Sanders.

  16. Gold Medal Award for Life Achievement in Psychology in the Public Interest: Bernice Lott

    ERIC Educational Resources Information Center

    American Psychologist, 2011

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in…

  17. Gold Medal Award for Life Achievement in the Practice of Psychology: Charles Silverstein

    ERIC Educational Resources Information Center

    American Psychologist, 2011

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in the…

  18. Gold Medal Award for Life Achievement in the Science of Psychology: Marcia K. Johnson

    ERIC Educational Resources Information Center

    American Psychologist, 2011

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in the…

  19. Gold Medal Award for Life Achievement in the Application of Psychology: Walter C. Borman

    ERIC Educational Resources Information Center

    American Psychologist, 2011

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in the…

  20. 77 FR 15997 - National Medal of Technology and Innovation Nomination Evaluation Committee Charter Renewal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-19

    ... United States Patent and Trademark Office National Medal of Technology and Innovation Nomination... Technology and Innovation Nomination Evaluation Committee on March 1, 2012. DATES: The Charter for the National Medal of Technology and Innovation Nomination Evaluation Committee was renewed on March 1,...

  1. Bowen, Dufek, and Shelly Receive 2012 James B. Macelwane Medals: Citation

    NASA Astrophysics Data System (ADS)

    Zachos, James

    2013-01-01

    Gabriel J. Bowen, Josef Dufek, and David Richard Shelly were awarded the 2012 James B. Macelwane Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is for "significant contributions to the geophysical sciences by an outstanding young scientist".

  2. Helping Eve overcome ADAM: G-quadruplexes in the ADAM-15 promoter as new molecular targets for breast cancer therapeutics.

    PubMed

    Brown, Robert V; Gaerig, Vanessa C; Simmons, Taesha; Brooks, Tracy A

    2013-12-05

    ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu function synergistically kills breast cancer cells, but to date there are no therapeutic options for decreasing ADAM-15 function or expression. In this vein, we have examined a unique string of guanine-rich DNA within the critical core promoter of ADAM-15. This region of DNA consists of seven contiguous runs of three or more consecutive guanines, which, under superhelical stress, can relax from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure. Using biophysical and biological techniques, we have examined the G4 formation within the entire and various truncated regions of the ADAM-15 promoter, and demonstrate strong intrastrand G4 formation serving to function as a biological silencer element. Characterization of the predominant G4 species formed within the ADAM-15 promoter will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics.

  3. A Disintegrin and Metalloproteinase10 (ADAM10) Regulates NOTCH Signaling during Early Retinal Development

    PubMed Central

    Toonen, Joseph A.; Ronchetti, Adam; Sidjanin, D. J.

    2016-01-01

    ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease) family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO) did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO) exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD) rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling. PMID:27224017

  4. Human and Murine Interleukin 23 Receptors Are Novel Substrates for A Disintegrin and Metalloproteases ADAM10 and ADAM17.

    PubMed

    Franke, Manuel; Schröder, Jutta; Monhasery, Niloufar; Ackfeld, Theresa; Hummel, Thorben M; Rabe, Björn; Garbers, Christoph; Becker-Pauly, Christoph; Floss, Doreen M; Scheller, Jürgen

    2016-05-13

    IL-23 (interleukin 23) regulates immune responses against pathogens and plays a major role in the differentiation and maintenance of TH17 cells and the development of autoimmune diseases and cancer. The IL-23 receptor (IL-23R) complex consists of the unique IL-23R and the common IL-12 receptor β1 (IL-12Rβ1). Differential splicing generates antagonistic soluble IL-23R (sIL-23R) variants, which might limit IL-23-mediated immune responses. Here, ectodomain shedding of human and murine IL-23R was identified as an alternative pathway for the generation of sIL-23R. Importantly, proteolytically released sIL-23R has IL-23 binding activity. Shedding of IL-23R was induced by stimulation with the phorbol ester phorbol 12-myristate 13-acetate (PMA), but not by ionomycin. PMA-induced shedding was abrogated by an ADAM (A disintegrin and metalloprotease) 10 and 17 selective inhibitor, but not by an ADAM10 selective inhibitor. ADAM17-deficient but not ADAM10-deficient HEK293 cells failed to shed IL-23R after PMA stimulation, demonstrating that ADAM17 but not ADAM10 cleaves the IL-23R. Constitutive shedding was, however, inhibited by an ADAM10 selective inhibitor. Using deletions and specific amino acid residue exchanges, we identified critical determinants of ectodomain shedding within the stalk region of the IL-23R. Finally, interaction studies identified domains 1 and 3 of the IL-23R as the main ADAM17 binding sites. In summary, we describe human and murine IL-23R as novel targets for protein ectodomain shedding by ADAM10 and ADAM17.

  5. Adam Paulsen, a Pioneer in Auroral Research

    NASA Astrophysics Data System (ADS)

    Jørgensen, Torben S.; Rasmussen, Ole

    2006-02-01

    The 20 to 30 years following the first International Polar Year in 1882-1883 was a period of quickly advancing knowledge and understanding of auroral phenomena. This was the time when hypotheses of aurora being due to, for example, reflections of fires from the interior of the Earth or sunlight from ice particles were abandoned and replaced by the mechanism of precipitating electrons. One of the auroral researchers at that time was the Dane Adam Frederik Wivet Paulsen (1833-1907). However, when reading literature about auroral history, his ideas and work do not seem to have attracted much interest outside his own and neighboring countries. For example, in his sweeping historical account Majestic Lights: The Aurora in Science, History, and the Arts [1980], author Robert Eather only referred to Paulsen in a couple of lines.

  6. John Adams and CERN: Personal Recollections

    NASA Astrophysics Data System (ADS)

    Brianti, G.; Plane, D. E.

    2014-02-01

    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.

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

    SciTech Connect

    Ungerer, Christopher; Doberstein, Kai; Boehm, Beate; Pfeilschifter, Josef; Mihic-Probst, Daniela; Gutwein, Paul

    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.

  8. TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization.

    PubMed

    Jouannet, Stéphanie; Saint-Pol, Julien; Fernandez, Laurent; Nguyen, Viet; Charrin, Stéphanie; Boucheix, Claude; Brou, Christel; Milhiet, Pierre-Emmanuel; Rubinstein, Eric

    2016-05-01

    The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. PMID:26686862

  9. Bradford H. Hager Receives 2013 Inge Lehmann Medal: Citation

    NASA Astrophysics Data System (ADS)

    Mitrovica, Jerry X.

    2014-01-01

    In the post-plate tectonics world, efforts to map the structure of Earth's interior broadened to include a growing preoccupation with the underlying dynamics. Students of global geophysics recognize the important role that previous recipients of the Inge Lehmann Medal played in this effort, but they would also understand the reasons that Bradford Hager of the Massachusetts Institute of Technology must be included in this honored list. Brad has been a central figure in mantle dynamics for the last 30 years, responsible for many fundamental advances in our understanding of mantle structure and flow and their connection to the geological record.

  10. Adams v. Bennett and Women's Equity Action League v. Bennett.

    ERIC Educational Resources Information Center

    Pratt, John H.

    1988-01-01

    Responding to requests to appeal Adams v. Bennett and Women's Equity Action League v. Bennett, both dealing with alleged illegal granting of federal funds, Judge Pratt decided that the plaintiffs in both cases lacked standing to continue their litigation. (BJV)

  11. 7. Historic American Buildings Survey, C. C. Adams, Photographer August ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    7. Historic American Buildings Survey, C. C. Adams, Photographer August 1931, SEED PACKING ROOM, Gift of New York State Department of Education. - Shaker North Family Washhouse (first), Shaker Road, New Lebanon, Columbia County, NY

  12. Group sequential monitoring based on the weighted log-rank test statistic with the Fleming-Harrington class of weights in cancer vaccine studies.

    PubMed

    Hasegawa, Takahiro

    2016-09-01

    In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log-rank tests with the Fleming-Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming-Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long-term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log-rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.

  13. Canup, Sigman, and Thompson Receive 2004 James B. Macelwane Medal

    NASA Astrophysics Data System (ADS)

    Halliday, Alexander; Bender, Michael L.; Randall, David A.

    2005-01-01

    Robin M. Canup, Daniel Sigman, and David W. J. Thompson received the Macelwane Medal at the 2004 Fall Meeting Honors Ceremony on 15 December, in San Francisco, California. The medal is given for significant contributions to the geophysical sciences by a young scientist of outstanding ability. Citation for Robin M. Canup. It is a great honor to introduce Robin Canup as a recipient of this distinguished and richly deserved award. Robin studies the formation of planets and their satellites-a subject of intrinsic significance and current fascination. As astrophysicists accumulate evidence of planets around other stars, the question of how to make a solar system like our own has yet to be answered. This tough and complex issue has been tackled by geochemists, but just as importantly by a select number of theoretical astrophysicists who deduce the dynamics of accretion. Robin is a relatively new player in this elite group, but her work has put her at the forefront. There are several important contributions one could highlight.

  14. ADAM17 substrate release in proximal tubule drives kidney fibrosis

    PubMed Central

    Kefaloyianni, Eirini; Muthu, Muthu Lakshmi; Kaeppler, Jakob; Sun, Xiaoming; Sabbisetti, Venkata; Chalaris, Athena; Rose-John, Stefan; Wong, Eitan; Sagi, Irit; Waikar, Sushrut S.; Rennke, Helmut; Bonventre, Joseph V.

    2016-01-01

    Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates’ receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor–treated WT mice, or mice with inducible KO of ADAM17 in proximal tubule (Slc34a1-Cre) were significantly protected against these effects. In vitro, in proximal tubule cells, we show that AREG has unique profibrotic actions that are potentiated by TNFα-induced AREG cleavage. In vivo, in acute kidney injury (AKI) and chronic kidney disease (CKD, fibrosis) patients, soluble AREG is indeed highly upregulated in human urine, and both ADAM17 and AREG expression show strong positive correlation with fibrosis markers in related kidney biopsies. Our results indicate that targeting of the ADAM17 pathway represents a therapeutic target for human kidney fibrosis. PMID:27642633

  15. The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

    PubMed Central

    Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T.; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

    2015-01-01

    ABSTRACT Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. PMID:25616895

  16. ADAM17 substrate release in proximal tubule drives kidney fibrosis

    PubMed Central

    Kefaloyianni, Eirini; Muthu, Muthu Lakshmi; Kaeppler, Jakob; Sun, Xiaoming; Sabbisetti, Venkata; Chalaris, Athena; Rose-John, Stefan; Wong, Eitan; Sagi, Irit; Waikar, Sushrut S.; Rennke, Helmut; Humphreys, Benjamin D.; Bonventre, Joseph V.; Herrlich, Andreas

    2016-01-01

    Kidney fibrosis following kidney injury is an unresolved health problem and causes significant morbidity and mortality worldwide. In a study into its molecular mechanism, we identified essential causative features. Acute or chronic kidney injury causes sustained elevation of a disintegrin and metalloprotease 17 (ADAM17); of its cleavage-activated proligand substrates, in particular of pro-TNFα and the EGFR ligand amphiregulin (pro-AREG); and of the substrates’ receptors. As a consequence, EGFR is persistently activated and triggers the synthesis and release of proinflammatory and profibrotic factors, resulting in macrophage/neutrophil ingress and fibrosis. ADAM17 hypomorphic mice, specific ADAM17 inhibitor–treated WT mice, or mice with inducible KO of ADAM17 in proximal tubule (Slc34a1-Cre) were significantly protected against these effects. In vitro, in proximal tubule cells, we show that AREG has unique profibrotic actions that are potentiated by TNFα-induced AREG cleavage. In vivo, in acute kidney injury (AKI) and chronic kidney disease (CKD, fibrosis) patients, soluble AREG is indeed highly upregulated in human urine, and both ADAM17 and AREG expression show strong positive correlation with fibrosis markers in related kidney biopsies. Our results indicate that targeting of the ADAM17 pathway represents a therapeutic target for human kidney fibrosis.

  17. ADAM10 as a target for anti-cancer therapy.

    PubMed

    Moss, Marcia L; Stoeck, Alexander; Yan, Wenbo; Dempsey, Peter J

    2008-02-01

    There is a great unmet medical need in the area of cancer treatment. A potential therapeutic target for intervention in cancer is ADAM10. ADAM10 is a disintegrin-metalloproteinase that processes membrane bound proteins from the cell surface to yield soluble forms. Pharmaceutical companies are actively seeking out inhibitors of ADAM10 for treatments in cancer as the enzyme is known to release the ErbB receptor, HER2/ErbB2 from the cell membrane, an event that is necessary for HER2 positive tumor cells to proliferate. ADAM10 is also capable of processing betacellulin indicating that an inhibitor could be used against EGFR/ErbB1 and/or HER4/ErbB4 receptor positive tumor cells that are betacellulin-dependent. ADAM10 is the principle sheddase for several other molecules associated with cancer proliferation, differentiation, adhesion and migration such as Notch, E-cadherin, CD44 and L1 adhesion molecule indicating that targeting ADAM10 with specific inhibitors could be beneficial.

  18. Adam Politzer-Father of Modern Otology.

    PubMed

    Dhungat, J V Pai; Gore, Geeta

    2015-09-01

    Adam Politzer (1835-1920) was born in Alberti near the city of Budapest in Hungary. He studied medicine at the University of Vienna and obtained his Doctorate degree in 1859. Some of his teachers belonged to the famous second "Vienna School" such as Joseph Skoda, Karl Rokitansky, Von Hebra, Josef Hyrtil, Johann Von Oppolzer and famous physiologist Carl Ludwig -who took special interest in him and was influential in his subsequent career. Politzer showed unusual interest in diseases of the ear and started to work in Carl Ludwig's laboratory. His interest at that time was mainly the physics of the auditory system. He studied the innervations of the intrinsic muscles of the ear There he was the first to demonstrate that the innervations of the tensor tympani muscle was by trigeminal nerve and that of the stapedial muscle was by facial nerve. He studied the air movement in the Eustachian tube and variation of air pressure in the tympanic cavity by connecting two manometers- one placed in the external auditory canal meatus, and another in the pharynx. He showed valve near the opening into the middle ear which controls the process. It is usually closed to keep the bacteria and other things away from the mouth and nose. PMID:27608882

  19. TACE (ADAM17) inhibits Schwann cell myelination.

    PubMed

    La Marca, Rosa; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M Laura; Wrabetz, Lawrence; Blobel, Carl P; Quattrini, Angelo; Salzer, James L; Taveggia, Carla

    2011-06-12

    Tumor necrosis factor-α-converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS.

  20. NCI’s Douglas R. Lowy and John T. Schiller awarded Sabin Medal

    Cancer.gov

    NCI scientists whose discovery provided the technology for commercially developed HPV vaccines were honored with the prestigious Albert B. Sabin Gold Medal Award at a ceremony held at the Sabin Vaccine Institute, May 18, 2011.

  1. Gold Medal Award for Life Achievement in the Application of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2007

    2007-01-01

    Announces the 2007 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology: McCay Vernon. A brief biography, highlighting areas of special focus in Vernon's work, is provided.

  2. Gold Medal Award for Life Achievement in the Science of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2007

    2007-01-01

    This article announces the 2007 recipient of the Gold Medal Award for Life Achievement in the Science of Psychology: Irving I. Gottesman. A brief biography, highlighting areas of special focus in Gottesman's work, is provided.

  3. Gold Medal Award for Life Achievement in the Practice of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2007

    2007-01-01

    Announces the 2007 recipient of the Gold Medal Award for Life Achievement in the Practice of Psychology: Patricia M. Bricklin. A brief biography, highlighting areas of special focus in Bricklin's work, is provided.

  4. National Medal of Technology Awarded to NCI Drs. Lowy and Schiller

    Cancer.gov

    President Obama announced that two NCI scientists would be recipients of the National Medal of Technology and Innovation -- the nation's highest honor for technological achievement. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO)

  5. ADAM12 induces estrogen-independence in breast cancer cells.

    PubMed

    Roy, Roopali; Moses, Marsha A

    2012-02-01

    Antiestrogen therapy has been used successfully to prolong disease-free and overall survival of ER positive breast cancer patients. However, 50% of patients with ER+ tumors fail to respond to such therapy or eventually acquire resistance to endocrine therapy, resulting in tumor progression and mortality. It is imperative, therefore, to understand the mechanisms that lead to hormone refractory breast cancer in order to develop therapeutics that can modulate the resistance to antiestrogen therapy. The protease, ADAM12, can be detected in the urine of breast cancer patients and its levels correlate with disease status, stage, and cancer risk. Within the context of this study, the authors have investigated the role of the two distinct isoforms of ADAM12 in breast tumor cell proliferation and as potential mediators of endocrine resistance. Using stable clones of ADAM12-overexpressing MCF-7 cells, the authors analyzed proliferation rates of these ER+ breast tumor cells both in estrogen-depleted medium and in the presence of the antiestrogens, tamoxifen, and ICI 182,780. Acquired estrogen resistance in these cells was analyzed using phospho-RTK analysis. Upregulation and phosphorylation of proteins were detected via immunoprecipitation and immunoblotting. EGFR and MAPK inhibitors were used to explore the mechanism of acquired estrogen resistance in breast tumor cells. It was observed that overexpression of the two isoforms, transmembrane ADAM12-L, and secreted ADAM12-S, in breast tumor cells promoted estrogen-independent proliferation. In ADAM12-L-expressing cells, estrogen-independence was a direct result of increased EGFR expression and MAPK activation, whereas, the mechanism in ADAM12-S-expressing cells may be enhanced IGF-1R signaling. The importance of the EGFR signaling pathway in the estrogen-independent growth of ADAM12-L expressing cells was highlighted by the effect of EGFR inhibitors AG1478 and PD15035 or MAPK inhibitor U0126, each of which abolished the

  6. NCI Scientists Awarded National Medal of Technology and Innovation by President Obama | Poster

    Cancer.gov

    Two NCI scientists received the National Medal of Technology and Innovation, the nation’s highest honor for technological achievement. The award was announced by President Obama in October. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO), Center for Cancer Research, NCI, and Douglas Lowy, M.D., also from LCO and NCI deputy director, received their medals at a White House ceremony on Nov. 20.

  7. Gold Medal Award for life achievement in psychology in the public interest.

    PubMed

    2013-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2013 recipient of the Gold Medal Award for Life Achievement in Psychology in the Public Interest is Jacquelynne S. Eccles. This article presents Eccles' award citation, a brief biography, and a selected bibliography.

  8. Gold Medal Award for life achievement in the practice of psychology.

    PubMed

    2013-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2013 recipient of the Gold Medal Award for Life Achievement in the Practice of Psychology is Patrick H. DeLeon. This article presents DeLeon's award citation, a brief biography, and a selected bibliography.

  9. Gold Medal Award for life achievement in the application of psychology.

    PubMed

    2013-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2013 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology is Frank L. Schmidt. This article presents Schmidt's award citation, a brief biography, and a selected bibliography.

  10. Gold Medal Award for life achievement in the science of psychology.

    PubMed

    2013-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2013 recipient of the Gold Medal Award for Life Achievement in the Science of Psychology is Elizabeth F. Loftus. This article presents Loftus' award citation, a brief biography, and a selected bibliography.

  11. Gold Medal Award for Life Achievement in the Science of Psychology.

    PubMed

    2008-01-01

    The American Psychological Foundation (APA) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2008 recipient of the American Psychological Foundation (APF) Gold Medal Award for Life Achievement in the Science of Psychology is Alice H. Eagly. A citation, biography, and selected bibliography for Alice H. Eagly are provided in this article. PMID:18665670

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Characterization of Mammalian ADAM2 and Its Absence from Human Sperm

    PubMed Central

    Choi, Heejin; Jin, Sora; Kwon, Jun Tae; Kim, Jihye; Jeong, Juri; Kim, Jaehwan; Jeon, Suyeon; Park, Zee Yong; Jung, Kang-Jin; Park, Kwangsung; Cho, Chunghee

    2016-01-01

    The members of the ADAM (a disintegrin and metalloprotease) family are membrane-anchored multi-domain proteins that play prominent roles in male reproduction. ADAM2, which was one of the first identified ADAMs, is the best studied ADAM in reproduction. In the male germ cells of mice, ADAM2 and other ADAMs form complexes that contribute to sperm-sperm adhesion, sperm-egg interactions, and the migration of sperm in the female reproductive tract. Here, we generated specific antibodies against mouse and human ADAM2, and investigated various features of ADAM2 in mice, monkeys and humans. We found that the cytoplasmic domain of ADAM2 might enable the differential association of this protein with other ADAMs in mice. Western blot analysis with the anti-human ADAM2 antibodies showed that ADAM2 is present in the testis and sperm of monkeys. Monkey ADAM2 was found to associate with chaperone proteins in testis. In humans, we identified ADAM2 as a 100-kDa protein in the testis, but failed to detect it in sperm. This is surprising given the results in mice and monkeys, but it is consistent with the failure of ADAM2 identification in the previous proteomic analyses of human sperm. These findings suggest that the reproductive functions of ADAM2 differ between humans and mice. Our protein analysis showed the presence of potential ADAM2 complexes involving yet-unknown proteins in human testis. Taken together, our results provide new information regarding the characteristics of ADAM2 in mammalian species, including humans. PMID:27341348

  14. Bernard J. Wood Receives 2013 Harry H. Hess Medal: Response

    NASA Astrophysics Data System (ADS)

    Wood, Bernard J.

    2014-01-01

    President Finn, friends, and colleagues, I am truly delighted to accept the Hess Medal for 2013. It is difficult to express one's feelings adequately on receipt of such a prestigious award, but a mixture of pride, humility, and thankfulness for a long and lucky career all occur. It did not start propitiously as my high school grades would only ensure undergraduate entry into the Northern Polytechnic, a second-tier institution in London. Nevertheless, I was enthused by several great teachers, including John Charalambous (inorganic chemistry) and Stephen Morel, a field geologist who had worked for many years in Malawi. They pushed me into trying for graduate school, and I was fortunate to find the eclectic Roger Strens my supervisor at Newcastle.

  15. Nicholson Medal for Human Outreach Talk: Physics Outreach: Social Benefits

    NASA Astrophysics Data System (ADS)

    Benczer-Koller, Noemie

    2011-04-01

    Physics constitutes a scientific endeavour that has benefited particularly from the globalization of our planet and the international character of its practitioners. The Medal Award was created by friends of Dwight Nicholson to highlight achievements in humanitarian service, special mentorship of students and junior colleagues while motivating interest in physics in the general public, outreach to the larger community of scientists and nonscientists, and work towards achieving gender and minority equity in the work force. While these are broad goals, they uniquely match the interests of practicing physicists as they weave seamlessly with their scientific work. Examples of the variety of such engagement in the physics community in the present time as well as in the past will be presented.

  16. Nominations sought for U.S. National Medal of Science

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-01-01

    Nominations are now being accepted for the 2012 U.S. National Medal of Science, which is the nation's highest honor for American scientists and engineers, presented annually by the president. The award is given to individuals “deserving of special recognition by reason of their outstanding cumulative contributions to knowledge” in the physical, biological, chemical, mathematical, engineering, or behavioral or social sciences, in combination with exemplary service to the nation, according to the program, which is administered by the National Science Foundation (NSF) on behalf of the White House Office of Science and Technology Policy. A note in NSF's call for nominations states, “We are especially interested in identifying women, members of minority groups, and persons with disabilities for consideration.”

  17. FAST{_}AD Code Verification: A Comparison to ADAMS

    SciTech Connect

    Buhl, M.L.; Wright, A.D.; Pierce, K.G.

    2001-02-15

    The National Renewable Energy Laboratory's National Wind Technology Center (NWTC) has refocused its wind turbine design-code comparison effort to verify FAST{_}AD with ADAMS. FAST{_}AD is a wind turbine structural-response code developed by Oregon State University for the NWTC. ADAMS is a commercial, general-purpose, multibody-dynamics code developed by Mechanical Dynamics, Inc. ADAMS, which is used in many industries, has been rigorously tested. Both ADAMS and FAST{_}AD use the AeroDyn subroutine package for calculating aerodynamic forces. The University of Utah developed AeroDyn for the NWTC. To compare FAST{_}AD to ADAMS, we modeled a rough approximation of the AWT-27 P4 turbine, using the same properties for both simulators. The AWT-27 is a 275-kilowatt (kW), two-bladed wind turbine. We also created three-bladed versions of the turbine models to verify FAST{_}AD for three-bladed turbines. In this paper, we list the aerodynamic features used in the comparison. We also explain how the programs model the turbine structure, describe the degrees of freedom (DOFs) used for this study, and present simulation comparisons that show very good agreement.

  18. Phosphatidylserine exposure is required for ADAM17 sheddase function

    PubMed Central

    Sommer, Anselm; Kordowski, Felix; Büch, Joscha; Maretzky, Thorsten; Evers, Astrid; Andrä, Jörg; Düsterhöft, Stefan; Michalek, Matthias; Lorenzen, Inken; Somasundaram, Prasath; Tholey, Andreas; Sönnichsen, Frank D.; Kunzelmann, Karl; Heinbockel, Lena; Nehls, Christian; Gutsmann, Thomas; Grötzinger, Joachim; Bhakdi, Sucharit; Reiss, Karina

    2016-01-01

    ADAM17, a prominent member of the ‘Disintegrin and Metalloproteinase' (ADAM) family, controls vital cellular functions through cleavage of transmembrane substrates. Here we present evidence that surface exposure of phosphatidylserine (PS) is pivotal for ADAM17 to exert sheddase activity. PS exposure is tightly coupled to substrate shedding provoked by diverse ADAM17 activators. PS dependency is demonstrated in the following: (a) in Raji cells undergoing apoptosis; (b) in mutant PSA-3 cells with manipulatable PS content; and (c) in Scott syndrome lymphocytes genetically defunct in their capacity to externalize PS in response to intracellular Ca2+ elevation. Soluble phosphorylserine but not phosphorylcholine inhibits substrate cleavage. The isolated membrane proximal domain (MPD) of ADAM17 binds to PS but not to phosphatidylcholine liposomes. A cationic PS-binding motif is identified in this domain, replacement of which abrogates liposome-binding and renders the protease incapable of cleaving its substrates in cells. We speculate that surface-exposed PS directs the protease to its targets where it then executes its shedding function. PMID:27161080

  19. Structural Characterization of the Ectodomain of a Disintegrin and Metalloproteinase-22 (ADAM22), a Neural Adhesion Receptor Instead of Metalloproteinase INSIGHTS ON ADAM FUNCTION

    SciTech Connect

    Liu, Heli; Shim, Ann H.R.; He, Xiaolin

    2009-12-01

    ADAMs (adisintegrin and metalloproteinases) are a family of multidomain transmembrane glycoproteins with diverse roles in physiology and diseases, with several members being drug targets for cancer and inflammation therapies. The spatial organization of the ADAM extracellular segment and its influence on the function of ADAMs have been unclear. Although most members of the ADAM family are active zinc metalloproteinases, 8 of 21 ADAMs lack functional metalloproteinase domains and are implicated in protein-protein interactions instead of membrane protein ectodomain shedding. One of such non-proteinase ADAMs, ADAM22, acts as a receptor on the surface of the postsynaptic neuron to regulate synaptic signal transmission. The crystal structure of the full ectodomain of mature human ADAM22 shows that it is a compact four-leaf clover with the metalloproteinase-like domain held in the concave face of a rigid module formed by the disintegrin, cysteine-rich, and epidermal growth factor-like domains. The loss of metalloproteinase activity is ensured by the absence of critical catalytic residues, the filling of the substrate groove, and the steric hindrance by the cysteine-rich domain. The structure, combined with calorimetric experiments, suggests distinct roles of three putative calcium ions bound to ADAM22, with one in the metalloproteinase-like domain being regulatory and two in the disintegrin domain being structural. The metalloproteinase-like domain contacts the rest of ADAM22 with discontinuous, hydrophilic, and poorly complemented interactions, suggesting the possibility of modular movement of ADAM22 and other ADAMs. The ADAM22 structure provides a framework for understanding how different ADAMs exert their adhesive function and shedding activities.

  20. Disturbed follicular architecture in B cell ADAM10 knockouts is mediated by compensatory increases in ADAM17 and TNFα shedding1

    PubMed Central

    Folgosa, Lauren; Zellner, Hannah B.; Shikh, Mohey Eldin El; Conrad, Daniel H.

    2013-01-01

    B cell ADAM10 is required for the development and maintenance of proper secondary lymphoid tissue architecture; however, the underlying mechanism remains unclear. In this study, we show disturbances in naïve lymph node architecture from B cell specific ADAM10 deficient mice (ADAM10B−/−) including loss of B/T compartmentalization, attenuation of FDC reticula, excessive collagen deposition, and increased HEV formation. Because TNFα signaling is critical for secondary lymphoid tissue architecture, we examined compensatory changes in ADAM17 and TNFα in ADAM10B−/− B cells. Surprisingly, defective follicular development in these mice was associated with increased rather than decreased TNFα expression. Here, we describe an increase in TNFα message, mRNA stability, soluble protein release, and membrane expression in ADAM10B−/− B cells compared to WT, which coincides with increased ADAM17 message and protein. To assess the mechanistic contribution of excessive TNFα to abnormal lymphoid architecture in ADAM10B−/− mice, we performed a bone marrow reconstitution study. Rectification of WT architecture was noted only in irradiated WT mice reconstituted with ADAM10B−/− + TNFKO bone marrow due to normalization of TNFα levels not seen in ADAM10B−/− alone. We conclude that ADAM17 overcompensation causes excessive TNFα shedding and further upregulation of TNFα expression, creating an aberrant signaling environment within B cell cortical regions of ADAM10B−/− lymph nodes, highlighting a key interplay between B cell ADAM10 and ADAM17 with respect to TNFα homeostasis. PMID:24227779

  1. The MIT/WHOI Joint Program in Oceanography and Applied Ocean Science and Engineering: An Ongoing Experiment in Graduate Education and the Sverdrup, Johnson and Fleming Influence.

    NASA Astrophysics Data System (ADS)

    Farrington, J. W.

    2002-12-01

    On May 8, 1968 Paul M. Fye, President of Woods Hole Oceanographic Institution and Howard W. Johnson, President of Massachusetts Institute of Oceanography, signed a Memorandum of Agreement of one and one-half pages in which both partner institutions "have each approved the creation of a Joint Graduate Program in Oceanography for which there will be established appropriate graduate degrees to be conferred jointly by the Massachusetts Institute of Technology and Woods Hole Oceanographic Institution." The partnership brought together the MIT experience with formal graduate education in sciences and engineering involving classroom instruction and more traditional academic advising with the less formal one to one "apprenticeship" or European tutorial style of education at WHOI. During the first year the graduate program involved only the physical sciences with the MIT home being in the Earth, Atmospheric and Planetary Sciences Department. Ocean Engineering was added the following year with the MIT home being the Ocean Engineering Department. Biological Oceanography was added in 1970 with the MIT home being the Biology Department. The existing graduate curricula of the home departments at MIT, the inclusion of ocean engineering, and the fact that several of the early program instructors and advisers at WHOI entered oceanography after formal graduate training in more traditional disciplines such as chemistry, geology, physics, biology and mathematics was not conducive to an automatic adoption of the Sverdrup, Johnson and Fleming paradigm of core courses that predominated in other leading graduate programs in oceanography. Despite this caveat, the Sverdrup, Johnson and Fleming paradigm has influenced the learning environment in the Joint Program. Taking into account lessons learned in the process, some suggestions for the future of graduate education in ocean sciences and ocean engineering will be presented.

  2. The Adam language: Ada extended with support for multiway activities

    NASA Technical Reports Server (NTRS)

    Charlesworth, Arthur

    1993-01-01

    The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

  3. Aberrant ADAM10 expression correlates with osteosarcoma progression

    PubMed Central

    2014-01-01

    Background Osteosarcoma is the most common type of bone cancer and is notorious for its rapid progression. The Notch signaling pathway has recently been shown to be involved in osteosarcoma. As a major sheddase of Notch receptors, ADAM10 has been implicated in many types of cancers, but its role in osteosarcoma has not been investigated. Previous studies have shown that the expression of CD31 was significantly elevated in metastatic osteosarcoma; however, its expression in nonmetastatic groups is not known. In addition, the mysterious multinucleated giant cell in giant cell-rich osteosarcoma was previously regarded as an osteoclast-like cell, but its exact identity is unclear. Method Tissue chip samples from 40 cases of nonmetastatic osteosarcoma were stained for cytoplasmic ADAM10, activated Notch1 and CD31. Osteoclasts in tumor sections were also stained for tartrate-resistant acid phosphatase (TRAP). Results Immunofluorescence staining revealed that ADAM10 expression significantly increased with the progression of osteosarcoma as well as in osteoblastic osteosarcoma, whereas the expression of the Notch intracellular domain (NICD) and CD31 was not significantly altered between different pathological stages. In addition, multinucleated giant cells in giant cell-rich osteosarcoma were also found to coexpress CD31, ADAM10 and NICD, but were negative for TRAP staining. Conclusions Our results highlight the importance of ADAM10 in the progression of osteosarcoma and suggest that the protein might be a potential therapeutic target in osteosarcoma treatment. This study also demonstrates that the multinucleated giant cell is an angiogenic tumor cell, rather than an osteoclast, and involves ADAM10/Notch1 signaling activation. PMID:24548763

  4. 77 FR 60004 - Culturally Significant Object Imported for Exhibition Determinations: “Wtewael's Adam and Eve”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Object Imported for Exhibition Determinations: ``Wtewael's Adam and Eve'' SUMMARY... object to be included in the exhibition ``Wtewael's Adam and Eve,'' imported from abroad for...

  5. Jefferson and Adams on the mind-body problem.

    PubMed

    Robinson, Daniel N

    2003-08-01

    Amidst the voluminous correspondence between Thomas Jefferson and John Adams are several letters pertaining to the material basis of mental life. These reveal in a most suggestive way the substantial differences between them. Well informed on prevailing scientific and philosophical perspectives, Jefferson and Adams used the issue to express their positions on the nature and limits of knowledge, the relative authority of scientific methods and speculations, and the larger question of human perfectibility. At the same time, their exchanges illuminate the prevailing and divergent perspectives on human psychology adopted by major leaders of thought in the New World.

  6. "Remember to Hand out Medals": Peer Rating and Expertise in a Question-and-Answer Study Group

    ERIC Educational Resources Information Center

    Ponti, Marisa

    2015-01-01

    This article reports on an exploratory study of giving medals as part of a peer rating system in a question-and-answer (Q&A) study group on Python, a programming language. There are no professional teachers tutoring learners. The study aimed to understand whether and how medals, awarded to responses in a peer-based learning environment, can…

  7. 45 CFR 2102.11 - Scope and content of submissions for proposed medals, insignia, coins, seals, and the like.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Procedures on Submissions of Plans or Designs § 2102.11 Scope and content of submissions for proposed medals, insignia, coins, seals, and the like. Each submission of the design for a proposed item which is within the... medals, insignia, coins, seals, and the like. 2102.11 Section 2102.11 Public Welfare Regulations...

  8. 45 CFR 2102.11 - Scope and content of submissions for proposed medals, insignia, coins, seals, and the like.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Procedures on Submissions of Plans or Designs § 2102.11 Scope and content of submissions for proposed medals, insignia, coins, seals, and the like. Each submission of the design for a proposed item which is within the... medals, insignia, coins, seals, and the like. 2102.11 Section 2102.11 Public Welfare Regulations...

  9. 75 FR 28782 - Extension of Period for Nominations to the National Medal of Technology and Innovation Nomination...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-24

    ... United States Patent and Trademark Office Extension of Period for Nominations to the National Medal of..., 2010, as well as from this notice of extension and from other sources. The SUPPLEMENTARY INFORMATION... National Medal of Technology and Innovation; presidents or distinguished faculty of universities; or...

  10. John Adams High School First Year Report, 1969-1970.

    ERIC Educational Resources Information Center

    Adams High School, Portland, OR.

    This report is an assessment of the events of the first year of operation of John Adams High School, Portland, Oregon. The primary goal of the school was to provide an educational experience relevant to the needs and interests of all adolescents, regardless of their intentions about pursuing further formal education. The report is oriented toward…

  11. What Ever Happened to . . . John Adams High School?

    ERIC Educational Resources Information Center

    Doremus, Richard R.

    1981-01-01

    First in a series, this article describes the rise and fall of John Adams High School, an experimental school in Portland (Oregon) that was recently closed after 12 years of operation. The experiences of those who tried to make the experiment work may help others interested in educational innovation. (WD)

  12. Research and Evaluation at John Adams High School.

    ERIC Educational Resources Information Center

    Adams High School, Portland, OR.

    We at Adams have committed ourselves (1) to search for new ways to make the inquiry into our own activities and the evaluation of our programs relevant and consistent with our notions of humanistic and personal education, and (2) to seek a mechanism for using research and evaluation to improve the operation of the school at every level and for…

  13. 3. Aerial view southeast, State Route 92 bottom left, Adams ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Aerial view southeast, State Route 92 bottom left, Adams Dam Road center, Brandywine Creek State Park and J. Chandler Farm in center left, duck pond bottom right and reservoir bottom left. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  14. 4. Aerial view southwest, Adams Dam Road bottom left, State ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    4. Aerial view southwest, Adams Dam Road bottom left, State Route 100 center, back gates to Winterthur and Wilmington Country Club upper center, duck pond and reservoir bottom right and center, and State Route 92 center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  15. 5. Aerial view west, Adams Dam Road bottom center, State ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. Aerial view west, Adams Dam Road bottom center, State Route 100 center, duck pond and reservoir center, State Route 100 center right, State Route 92 below center right, Brandywine Creek State Park center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

  16. An Informal Report on Collegiate Successes with "The Adams Chronicles."

    ERIC Educational Resources Information Center

    Goldsberry, Gary G.

    In the spring of 1976, "The Adams Chronicles", a bicentennial television course developed by Coast Community College District and the University of California at San Diego, was distributed to colleges nationwide at no charge with the understanding that each college would return information regarding promotion, enrollment, and form of offering this…

  17. Adam Smith and the Teaching of English Literature.

    ERIC Educational Resources Information Center

    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)

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

    ERIC Educational Resources Information Center

    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)

  19. ADAM: A Collaborative Effort To Prepare Future Administrators.

    ERIC Educational Resources Information Center

    Richardson, Michael D.; And Others

    ADAM (Administrative Development and Management), an administrator preparation partnership between Greenwood (South Carolina) School District 50 and Clemson University, is described in this paper. The program uses practicing administrators in collaboration with college faculty to train prospective school administrators. The purpose is to provide…

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

    PubMed Central

    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

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

    ERIC Educational Resources Information Center

    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…

  2. Cloning and expression of ADAM related metalloproteases in Equine Laminitis

    PubMed Central

    Coyne, Michael J.; Cousin, Hélène; Loftus, John P.; Johnson, Philip J.; Belknap, James K.; Gradil, Carlos M.; Black, Samuel J.; Alfandari, Dominique

    2010-01-01

    Equine laminitis is a debilitating disease affecting the digital laminae that suspends the distal phalanx within the hoof. While the clinical progression of the disease has been well documented, the molecular events associated with its pathogenesis remain largely unknown. We have investigated the expression of genes coding for proteins containing a Disintegrin and Metalloprotease domain (ADAM), as well as genes encoding the natural inhibitors of these enzymes (Tissue Inhibitor of MetalloProtease; TIMP) in horses with naturally acquired (acute, chronic and aggravated chronic cases collected in clinic) or experimentally-induced (black walnut extract and starch gruel models) laminitis using real time quantitative RT-PCR. Changes in expression of these enzymes and regulators may underlie the pathologic remodeling of lamellar tissue in laminitis. Genes encoding ADAMs involved in inflammation (ADAM-10 and ADAM-17), as well as those implicated in arthritis (ADAMTS-1, ADAMTS-4 and ADAMTS-5) were cloned, and the sequences used to generate specific oligonucleotide primers for the RT-qPCR experiments. Our results show that genes encoding ADAM-10 and 17 were not induced in most laminitic animals whereas ADAMTS-4 gene expression was strongly upregulated in practically all cases of experimentally induced and naturally acquired laminitis. The expression of MMP-9 and ADAMTS-5 was also increased in many of the laminitic horses. In addition, TIMP-2 gene expression was decreased in most laminitic horses, whereas expression of genes encoding other TIMPs, namely TIMP-1 and TIMP-3 was randomly increased or decreased in the various models. We conclude that elevated expression of lamellar ADAMTS-4 is a common feature of laminitis consistent with a central role of the gene product in the pathophysiology of laminitis. PMID:19131116

  3. Increased B Cell ADAM10 in Allergic Patients and Th2 Prone Mice.

    PubMed

    Cooley, Lauren Folgosa; Martin, Rebecca K; Zellner, Hannah B; Irani, Anne-Marie; Uram-Tuculescu, Cora; El Shikh, Mohey Eldin; Conrad, Daniel H

    2015-01-01

    ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared to Th1 prone controls. To further understand this regulation, ADAM17 and TNF were studied in C57Bl/6 and Balb/c mice deficient in ADAM10. C57-ADAM10B-/- were more adept at increasing ADAM17 levels and thus TNF cleavage resulting in excess follicular TNF levels and abnormal secondary lymphoid tissue architecture not noted in Balb-ADAM10B-/-. Moreover, the level of B cell ADAM10 as well as Th context is critical for determining IgE production potential. Using a murine house dust mite airway hypersensitivity model, we describe that high B cell ADAM10 level in a Th2 context (Balb/c WT) is optimal for disease induction including bronchoconstriction, goblet cell metaplasia, mucus, inflammatory cellular infiltration, and IgE production. Balb/c mice deficient in B cell ADAM10 have attenuated lung and airway symptoms compared to Balb WT and are actually most similar to C57 WT (Th1 prone). C57-ADAM10B-/- have even further reduced symptomology. Taken together, it is critical to consider both innate B cell levels of ADAM10 and ADAM17 as well as Th context when determining host susceptibility to allergic disease. High B cell ADAM10 and low ADAM17 levels would help diagnostically in predicting Th2 disease susceptibility; and, we provide support for the use ADAM10 inhibitors in treating Th2 disease.

  4. Gold Medal Award for Life Achievement in the Application of Psychology: David W. Johnson.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Application of Psychology is David W. Johnson. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record PMID:27504568

  5. Gold Medal Award for Life Achievement in the Practice of Psychology: Sandra L. Shullman.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Practice of Psychology is Sandra L. Shullman. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record PMID:27504569

  6. Gold Medal Award for Life Achievement in Psychology in the Public Interest: Beatrice A. Wright.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in 4 areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in Psychology in the Public Interest is Beatrice A. Wright. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are: Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record PMID:27504570

  7. Gold Medal Award for Life Achievement in the Science of Psychology: Richard E. Nisbett.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Science of Psychology is Richard E. Nisbett. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record PMID:27504571

  8. Gold Medal Award for life achievement in the science of psychology.

    PubMed

    2012-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2012 recipient of the Gold Medal Award for Life Achievement in the Science of Psychology is Philip G. Zimbardo. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 120th Annual Convention of the American Psychological Association on August 3, 2012, at 4:00 p.m. Members of the 2012 APF Board of Trustees are Dorothy W. Cantor, president; Charles L. Brewer, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; Brian N. Baird; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Connie Chan; William Howell; Anthony Jackson; Ronald F. Levant; Aurelio Prifitera; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  9. Gold Medal Award for Life Achievement in the Science of Psychology: Richard E. Nisbett.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Science of Psychology is Richard E. Nisbett. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record

  10. Gold Medal Award for Life Achievement in Psychology in the Public Interest: Beatrice A. Wright.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in 4 areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in Psychology in the Public Interest is Beatrice A. Wright. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are: Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record

  11. Gold Medal Award for Life Achievement in the Practice of Psychology: Sandra L. Shullman.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Practice of Psychology is Sandra L. Shullman. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record

  12. Gold Medal Award for Life Achievement in the Application of Psychology: David W. Johnson.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology. The 2016 recipient of Gold Medal Award for Life Achievement in the Application of Psychology is David W. Johnson. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record

  13. Gold Medal Award for life achievement in the application of psychology.

    PubMed

    2012-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2012 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology is Marsha Linehan. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 120th Annual Convention of the American Psychological Association on August 3, 2012, at 4:00 p.m. Members of the 2012 APF Board of Trustees are Dorothy W. Cantor, president; Charles L. Brewer, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; Brian N. Baird; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Connie Chan; William Howell; Anthony Jackson; Ronald F. Levant; Aurelio Prifitera; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  14. Gold Medal Award for life achievement in the practice of psychology.

    PubMed

    2012-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2012 recipient of the Gold Medal Award for Life Achievement in the Practice of Psychology is Carol D. Goodheart. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 120th Annual Convention of the American Psychological Association on August 3, 2012, at 4:00 p.m. Members of the 2012 APF Board of Trustees are Dorothy W. Cantor, president; Charles L. Brewer, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; Brian N. Baird; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Connie Chan; William Howell; Anthony Jackson; Ronald F. Levant; Aurelio Prifitera; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors' liaison.

  15. Gold medal award for life achievement in the application of psychology.

    PubMed

    2009-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2009 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology is Stuart Oskamp. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 117th Annual Convention of the American Psychological Association on August 7, 2009, at 4:00 p.m. Members of the 2009 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Archie L. Turner, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Anthony Jackson; Steven E. James; Ronald F. Levant; Gerald Koocher; Sandra Shullman; and Rosie Phillips Bingham, APA Board of Directors liaison.

  16. Gold medal award for life achievement in the science of psychology.

    PubMed

    2009-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2009 recipient of the Gold Medal Award for Life Achievement in the Science of Psychology is Mary K. Rothbart. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 117th Annual Convention of the American Psychological Association on August 7, 2009, at 4:00 p.m. Members of the 2009 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Archie L. Turner, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Anthony Jackson; Steven E. James; Ronald F. Levant; Gerald Koocher; Sandra Shullman; and Rosie Phillips Bingham, APA Board of Directors liaison.

  17. Gold medal award for life achievement in psychology in the public interest: Bernice Lott.

    PubMed

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in Psychology in the Public Interest is Bernice Lott. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 119th Annual Convention of the American Psychological Association on August 5, 2011, at 4:00 p.m. Members of the 2011 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow, Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Connie Chan; Anthony Jackson; Ronald F. Levant; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  18. Gold medal award for life achievement in the science of psychology: Marcia K. Johnson.

    PubMed

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in the Science of Psychology is Marcia K. Johnson. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 119th Annual Convention of the American Psychological Association on August 5, 2011, at 4:00 p.m. Members of the 2011 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow, Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Connie Chan; Anthony Jackson; Ronald F. Levant; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  19. Gold medal award for life achievement in the application of psychology: Walter C. Borman.

    PubMed

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in the Application of Psychology is Walter C. Borman. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 119th Annual Convention of the American Psychological Association on August 5, 2011, at 4:00 p.m. Members of the 2011 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow, Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Connie Chan; Anthony Jackson; Ronald F. Levant; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  20. Gold medal award for life achievement in psychology in the public interest.

    PubMed

    2009-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2009 recipient of the Gold Medal Award for Life Achievement in Psychology in the Public Interest is E. Scott Geller. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 117th Annual Convention of the American Psychological Association on August 7, 2009, at 4:00 p.m. Members of the 2009 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Archie L. Turner, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Anthony Jackson; Steven E. James; Ronald F. Levant; Gerald Koocher; Sandra Shullman; and Rosie Phillips Bingham, APA Board of Directors liaison.

  1. Gold medal award for life achievement in the practice of psychology: Charles Silverstein.

    PubMed

    2011-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in the Practice of Psychology is Charles Silverstein. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 119th Annual Convention of the American Psychological Association on August 5, 2011, at 4:00 p.m. Members of the 2011 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow, Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Connie Chan; Anthony Jackson; Ronald F. Levant; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  2. Fiber optic displacement sensor for medal detection using fiber bundled probe

    NASA Astrophysics Data System (ADS)

    Yasin, M.; Samian, Supadi, Pujiyanto, Yhuwana, Y. G. Yhun

    2016-03-01

    A simple fiber optic displacement sensor (FODS) based on intensity modulation technique is investigated using a bundle multimode plastic fiber as a probe for various medals detection. The sensor consists of a light source, a probe, and photodiode detector. The sensor is capable of measuring displacements of flat medals ranging from 0.05 to 4.2 mm using a red light source of wavelength 630 nm. The highest sensitivity of the sensor is found to be 0.0048 mV/μm over 50-650 µm for the gold medal. The sensor is highly sensitive at the front slope and very useful for close distance target. The simplicity of the design, high sensitivity, long dynamic range and the low cost of the fabrication make it suitable for wider applications in industries as position control and micro displacement measurement in the hazardous region.

  3. Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

    PubMed

    De Savi, Chris; Pape, Andrew; Sawyer, Yvonne; Milne, David; Davies, Chris; Cumming, John G; Ting, Attilla; Lamont, Scott; Smith, Peter D; Tart, Jonathon; Page, Ken; Moore, Peter

    2011-06-01

    A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics.

  4. Secretion-Positive LGI1 Mutations Linked to Lateral Temporal Epilepsy Impair Binding to ADAM22 and ADAM23 Receptors

    PubMed Central

    Dazzo, Emanuela; Belluzzi, Elisa; Malacrida, Sandro; Vitiello, Libero; Greggio, Elisa; Tosatto, Silvio C. E.

    2016-01-01

    Autosomal dominant lateral temporal epilepsy (ADTLE) is a focal epilepsy syndrome caused by mutations in the LGI1 gene, which encodes a secreted protein. Most ADLTE-causing mutations inhibit LGI1 protein secretion, and only a few secretion-positive missense mutations have been reported. Here we describe the effects of four disease-causing nonsynonymous LGI1 mutations, T380A, R407C, S473L, and R474Q, on protein secretion and extracellular interactions. Expression of LGI1 mutant proteins in cultured cells shows that these mutations do not inhibit protein secretion. This finding likely results from the lack of effects of these mutations on LGI1 protein folding, as suggested by 3D protein modelling. In addition, immunofluorescence and co-immunoprecipitation experiments reveal that all four mutations significantly impair interaction of LGI1 with the ADAM22 and ADAM23 receptors on the cell surface. These results support the existence of a second mechanism, alternative to inhibition of protein secretion, by which ADLTE-causing LGI1 mutations exert their loss-of-function effect extracellularly, and suggest that interactions of LGI1 with both ADAM22 and ADAM23 play an important role in the molecular mechanisms leading to ADLTE. PMID:27760137

  5. A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis

    PubMed Central

    Köhn-Gaone, Julia; Chalupsky, Karel; Lüllmann-Rauch, Renate; Barikbin, Roja; Bergmann, Juri; Wöhner, Birte; Zbodakova, Olga; Leuschner, Ivo; Martin, Gregor; Tiegs, Gisa; Rose-John, Stefan; Sedlacek, Radislav; Tirnitz-Parker, Janina E.E.; Saftig, Paul; Schmidt-Arras, Dirk

    2016-01-01

    A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its role in other tissues, ADAM10 is dispensable for the Notch2-dependent biliary tree formation. However, we demonstrate that expression of bile acid transporters is dependent on ADAM10. Consequently, mice deficient for Adam10 in hepatocytes, cholangiocytes and liver progenitor cells develop spontaneous hepatocyte necrosis and concomitant liver fibrosis. We furthermore observed a strongly augmented ductular reaction in 15-week old ADAM10Δhep/Δch mice and demonstrate that c-Met dependent liver progenitor cell activation is enhanced. Additionally, liver progenitor cells are primed to hepatocyte differentiation in the absence of ADAM10. These findings show that ADAM10 is a novel central node controlling liver tissue homeostasis. Highlights: Loss of ADAM10 in murine liver results in hepatocyte necrosis and concomitant liver fibrosis. ADAM10 directly regulates expression of bile acid transporters but is dispensable for Notch2-dependent formation of the biliary system. Activation of liver progenitor cells is enhanced through increased c-Met signalling, in the absence of ADAM10. Differentiation of liver progenitor cells to hepatocytes is augmented in the absence of ADAM10. PMID:26942887

  6. Role of ADAM33 gene and associated single nucleotide polymorphisms in asthma.

    PubMed

    Sharma, Neeraj; Tripathi, Priya; Awasthi, Shally

    2011-04-01

    Asthma is a multifactorial disorder, primarily resulting from interactions between genetic and environmental factors. ADAM33 gene (located on chromosome 20p13) has been reported to play an important role in asthma. This review article is intended to include all of the publications, to date, which have assessed the association of ADAM33 gene polymorphisms as well as have shown the role of ADAM33 gene in airway remodeling and their expression with asthma. A PubMed search was performed for studies published between 1990 and 2010. The terms "ADAM33," "ADAM33 gene and asthma," and "ADAM33 gene polymorphisms" were used as search criteria. Based on available literature we can only speculate its role in the morphogenesis and functions of the lung. Fourteen studies conducted in different populations were found showing an association of ADAM33 gene polymorphisms with asthma. However, none of the single nucleotide polymorphisms (SNPs) of ADAM33 gene had found association with asthma across all ethnic groups. Because higher expression of ADAM33 is found in the fibroblast and smooth muscle cells of the lung, over- or underexpression of ADAM33 gene may result in alterations in airway remodeling and repair processes. However, no SNP of ADAM33 gene showed significant associations with asthma across all ethnic groups; the causative polymorphism, if any, still has to be identified.

  7. ADAM17 Silencing in Mouse Colon Carcinoma Cells: The Effect on Tumoricidal Cytokines and Angiogenesis

    PubMed Central

    Das, Sudipta; Czarnek, Maria; Bzowska, Monika; Mężyk-Kopeć, Renata; Stalińska, Krystyna; Wyroba, Barbara; Sroka, Jolanta; Jucha, Jarosław; Deneka, Dawid; Stokłosa, Paulina; Ogonek, Justyna; Swartz, Melody A.; Madeja, Zbigniew; Bereta, Joanna

    2012-01-01

    ADAM17 (a disintegrin and metalloprotease 17) is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response. PMID:23251384

  8. ADAM17 silencing in mouse colon carcinoma cells: the effect on tumoricidal cytokines and angiogenesis.

    PubMed

    Das, Sudipta; Czarnek, Maria; Bzowska, Monika; Mężyk-Kopeć, Renata; Stalińska, Krystyna; Wyroba, Barbara; Sroka, Jolanta; Jucha, Jarosław; Deneka, Dawid; Stokłosa, Paulina; Ogonek, Justyna; Swartz, Melody A; Madeja, Zbigniew; Bereta, Joanna

    2012-01-01

    ADAM17 (a disintegrin and metalloprotease 17) is a major sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules and is often overexpressed in malignant cells. It is generally accepted that ADAM17 promotes tumor development via activating growth factors from the EGF family, thus facilitating autocrine stimulation of tumor cell proliferation and migration. Here we show, using MC38CEA murine colon carcinoma model, that ADAM17 also regulates tumor angiogenesis and cytokine profile. When ADAM17 was silenced in MC38CEA cells, in vivo tumor growth and in vitro cell motility were significantly diminished, but no effect was seen on in vitro cell proliferation. ADAM17-silencing was accompanied by decreased in vitro expression of vascular endothelial growth factor-A and matrix metalloprotease-9, which was consistent with the limited angiogenesis and slower growth seen in ADAM17-silenced tumors. Among the growth factors susceptible to shedding by ADAM17, neuregulin-1 was the only candidate to mediate the effects of ADAM17 on MC38CEA motility and tumor angiogenesis. Concentrations of TNF and IFNγ, cytokines that synergistically induced proapoptotic effects on MC38CEA cells, were significantly elevated in the lysates of ADAM17-silenced tumors compared to mock transfected controls, suggesting a possible role for ADAM17 in host immune suppression. These results introduce new, complex roles of ADAM17 in tumor progression, including its impact on the anti-tumor immune response.

  9. 50 years of space science (Jean Dominique Cassini Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Bonnet, Roger-Maurice

    2013-04-01

    The launch of Sputnik-1 triggered my fascination for space at the age of 20. The past 50 years have allowed me to study the Sun with sounding rockets and satellites, revealing the complexity of our star, contributing to the understanding of its physics, and offering surprising manifestations of its behavior and of its effects on Earth. Building instruments for space astronomy, managing teams of space scientists and engineers, led me to become the science director of the European space agency between 1983 and 2001 where I formulated and managed the Horizon 2000 program, which led Europe to occupy the front row of world space science. The Jean Dominique Cassini Medal Lecture offers me an opportunity, to describe the most spectacular achievements of this long-term plan and to outline some basic principles for reaching success, including the essential role of international cooperation with shared partnership. The Lecture also identifies key problems and controversial issues that space astronomy and exploration will face in the 21st century.

  10. High Glucose Up-regulates ADAM17 through HIF-1α in Mesangial Cells.

    PubMed

    Li, Renzhong; Uttarwar, Lalita; Gao, Bo; Charbonneau, Martine; Shi, Yixuan; Chan, John S D; Dubois, Claire M; Krepinsky, Joan C

    2015-08-28

    We previously showed that ADAM17 mediates high glucose-induced matrix production by kidney mesangial cells. ADAM17 expression is increased in diabetic kidneys, suggesting that its up-regulation may augment high glucose profibrotic responses. We thus studied the effects of high glucose on ADAM17 gene regulation. Primary rat mesangial cells were treated with high glucose (30 mm) or mannitol as osmotic control. High glucose dose-dependently increased ADAM17 promoter activity, transcript, and protein levels. This correlated with augmented ADAM17 activity after 24 h versus 1 h of high glucose. We tested involvement of transcription factors shown in other settings to regulate ADAM17 transcription. Promoter activation was not affected by NF-κB or Sp1 inhibitors, but was blocked by hypoxia-inducible factor-1α (HIF-1α) inhibition or down-regulation. This also prevented ADAM17 transcript and protein increases. HIF-1α activation by high glucose was shown by its increased nuclear translocation and activation of the HIF-responsive hypoxia-response element (HRE)-luciferase reporter construct. Assessment of ADAM17 promoter deletion constructs coupled with mutation analysis and ChIP studies identified HIF-1α binding to its consensus element at -607 as critical for the high glucose response. Finally, inhibitors of epidermal growth factor receptor (EGFR) and downstream PI3K/Akt, or ADAM17 itself, prevented high glucose-induced HIF-1α activation and ADAM17 up-regulation. Thus, high glucose induces ADAM17 transcriptional up-regulation in mesangial cells, which is associated with augmentation of its activity. This is mediated by HIF-1α and requires EGFR/ADAM17 signaling, demonstrating the potentiation by ADAM17 of its own up-regulation. ADAM17 inhibition thus provides a potential novel therapeutic strategy for the treatment of diabetic nephropathy.

  11. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    PubMed

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy. PMID:26176220

  12. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells

    PubMed Central

    Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W.; Swartz, Melody A.; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy. PMID:26176220

  13. ADAM17 Promotes Motility, Invasion, and Sprouting of Lymphatic Endothelial Cells.

    PubMed

    Mężyk-Kopeć, Renata; Wyroba, Barbara; Stalińska, Krystyna; Próchnicki, Tomasz; Wiatrowska, Karolina; Kilarski, Witold W; Swartz, Melody A; Bereta, Joanna

    2015-01-01

    Tumor-associated lymphatic vessels actively participate in tumor progression and dissemination. ADAM17, a sheddase for numerous growth factors, cytokines, receptors, and cell adhesion molecules, is believed to promote tumor development, facilitating both tumor cell proliferation and migration, as well as tumor angiogenesis. In this work we addressed the issue of whether ADAM17 may also promote tumor lymphangiogenesis. First, we found that ADAM17 is important for the migratory potential of immortalized human dermal lymphatic endothelial cells (LEC). When ADAM17 was stably silenced in LEC, their proliferation was not affected, but: (i) single-cell motility, (ii) cell migration through a 3D Matrigel/collagen type I matrix, and (iii) their ability to form sprouts in a 3D matrix were significantly diminished. The differences in the cell motility between ADAM17-proficient and ADAM17-silenced cells were eliminated by inhibitors of EGFR and HER2, indicating that ADAM17-mediated shedding of growth factors accounts for LEC migratory potential. Interestingly, ADAM17 depletion affected the integrin surface expression/functionality in LEC. ADAM17-silenced cells adhered to plastic, type I collagen, and fibronectin faster than their ADAM17-proficient counterparts. The difference in adhesion to fibronectin was abolished by a cyclic RGD peptide, emphasizing the involvement of integrins in the process. Using a soluble receptor array, we identified BIG-H3 among several candidate proteins involved in the phenotypic and behavioral changes of LEC upon ADAM17 silencing. In additional assays, we confirmed the increased expression of BIG-H3, as well as TGFβ2 in ADAM17-silenced LEC. The antilymphangiogenic effects of ADAM17 silencing in lymphatic endothelial cells suggest further relevance of ADAM17 as a potential target in cancer therapy.

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

    PubMed Central

    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

  15. Adams-Based Rover Terramechanics and Mobility Simulator - ARTEMIS

    NASA Technical Reports Server (NTRS)

    Trease, Brian P.; Lindeman, Randel A.; Arvidson, Raymond E.; Bennett, Keith; VanDyke, Lauren P.; Zhou, Feng; Iagnemma, Karl; Senatore, Carmine

    2013-01-01

    The Mars Exploration Rovers (MERs), Spirit and Opportunity, far exceeded their original drive distance expectations and have traveled, at the time of this reporting, a combined 29 kilometers across the surface of Mars. The Rover Sequencing and Visualization Program (RSVP), the current program used to plan drives for MERs, is only a kinematic simulator of rover movement. Therefore, rover response to various terrains and soil types cannot be modeled. Although sandbox experiments attempt to model rover-terrain interaction, these experiments are time-intensive and costly, and they cannot be used within the tactical timeline of rover driving. Imaging techniques and hazard avoidance features on MER help to prevent the rover from traveling over dangerous terrains, but mobility issues have shown that these methods are not always sufficient. ARTEMIS, a dynamic modeling tool for MER, allows planned drives to be simulated before commands are sent to the rover. The deformable soils component of this model allows rover-terrain interactions to be simulated to determine if a particular drive path would take the rover over terrain that would induce hazardous levels of slip or sink. When used in the rover drive planning process, dynamic modeling reduces the likelihood of future mobility issues because high-risk areas could be identified before drive commands are sent to the rover, and drives planned over these areas could be rerouted. The ARTEMIS software consists of several components. These include a preprocessor, Digital Elevation Models (DEMs), Adams rover model, wheel and soil parameter files, MSC Adams GUI (commercial), MSC Adams dynamics solver (commercial), terramechanics subroutines (FORTRAN), a contact detection engine, a soil modification engine, and output DEMs of deformed soil. The preprocessor is used to define the terrain (from a DEM) and define the soil parameters for the terrain file. The Adams rover model is placed in this terrain. Wheel and soil parameter files

  16. Adams-Oliver Syndrome: A Case with Full Expression

    PubMed Central

    Dehdashtian, Amir; Dehdashtian, Masoud

    2016-01-01

    Adams-Oliver syndrome (AOS) is characterized by the combination of congenital scalp defects (aplasia cutis congenita) and terminal transverse limb defects of variable severity. It is believed that Adams-Oliver syndrome without major organ abnormalities does not necessarily alter the normal lifespan. We present a case without detectable major organ abnormality contrary to life but with poor weight gain. A male infant with scalp and skin cutis aplasia, generalized cutis aplasia, dilated veins over scalp and trunk, hypoplastic toes and nails of feet, glaucoma, poor feeding and poor weight gain. This report shows a case of AOS without major multiple organ abnormalities but with poor feeding and abnormal weight gain that may be alter the normal lifespan. PMID:27433307

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

    PubMed

    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. Automatic Dynamic Aircraft Modeler (ADAM) for the Computer Program NASTRAN

    NASA Technical Reports Server (NTRS)

    Griffis, H.

    1985-01-01

    Large general purpose finite element programs require users to develop large quantities of input data. General purpose pre-processors are used to decrease the effort required to develop structural models. Further reduction of effort can be achieved by specific application pre-processors. Automatic Dynamic Aircraft Modeler (ADAM) is one such application specific pre-processor. General purpose pre-processors use points, lines and surfaces to describe geometric shapes. Specifying that ADAM is used only for aircraft structures allows generic structural sections, wing boxes and bodies, to be pre-defined. Hence with only gross dimensions, thicknesses, material properties and pre-defined boundary conditions a complete model of an aircraft can be created.

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

    PubMed

    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. PMID:21765569

  20. ADAM: An Axisymmetric Duct Aeroacoustic Modeling system. [aircraft turbofan engines

    NASA Technical Reports Server (NTRS)

    Abrahamson, A. L.

    1983-01-01

    An interconnected system of computer programs for analyzing the propagation and attenuation of sound in aeroengine ducts containing realistic compressible subsonic mean flows, ADAM was developed primarily for research directed towards the reduction of noise emitted from turbofan aircraft engines. The two basic components are a streamtube curvature program for determination of the mean flow, and a finite element code for solution of the acoustic propagation problem. The system, which has been specifically tailored for ease of use, is presently installed at NASA Langley Reseach Center on a Control Data Cyber 175 Computer under the NOS Operating system employing a Tektronix terminal for interactive graphics. The scope and organization of the ADAM system is described. A users guide, examples of input data, and results for selected cases are included.

  1. Application of the ADAMS program to deployable space truss structures

    NASA Technical Reports Server (NTRS)

    Calleson, R. E.

    1985-01-01

    The need for a computer program to perform kinematic and dynamic analyses of large truss structures while deploying from a packaged configuration in space led to the evaluation of several existing programs. ADAMS (automatic dynamic analysis of mechanical systems), a generalized program from performing the dynamic simulation of mechanical systems undergoing large displacements, is applied to two concepts of deployable space antenna units. One concept is a one cube folding unit of Martin Marietta's Box Truss Antenna and the other is a tetrahedral truss unit of a Tetrahedral Truss Antenna. Adequate evaluation of dynamic forces during member latch-up into the deployed configuration is not yet available from the present version of ADAMS since it is limited to the assembly of rigid bodies. Included is a method for estimating the maximum bending stress in a surface member at latch-up. Results include member displacement and velocity responses during extension and an example of member bending stresses at latch-up.

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

    PubMed Central

    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

  3. ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression

    PubMed Central

    Fritzsche, Florian R; Wassermann, Kirsten; Jung, Monika; Tölle, Angelika; Kristiansen, Ilka; Lein, Michael; Johannsen, Manfred; Dietel, Manfred; Jung, Klaus; Kristiansen, Glen

    2008-01-01

    Background A Disintegrin And Metalloprotease (ADAM) 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort. Methods 108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ2-test), correlations and univariate as well as multivariate survival analyses. Results ADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis. Conclusion ADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts. PMID:18582378

  4. ADAM-mediated amphiregulin shedding and EGFR transactivation

    PubMed Central

    Kasina, S.; Scherle, P. A.; Hall, C. L.; Macoska, J. A.

    2011-01-01

    Introduction The ectodomain shedding of epidermal growth factor receptor (EGFR) ligands, such as amphiregulin (AREG), by ADAMs (A Disintegrin And Metalloproteases) can be stimulated by G protein-coupled receptor (GPCR) agonists. Interactions between the CXCR4 GPCR and the CXCL12 chemokine have been shown to mediate gene transcription and cellular proliferation in non-transformed and transformed prostate epithelial cells, as well as motility/invasiveness in transformed cells. Objectives In this report, we investigated the ability of CXCL12 to stimulate amphiregulin ectodomain shedding in non-transformed and transformed prostate epithelial cells that respond proliferatively to sub-nanomolar levels of CXCL12 and amphiregulin. Materials and Methods Non-transformed N15C6 and transformed PC3 prostate epithelial cells were assessed for amphiregulin shedding, ADAM activation, Src phosphorylation and EGFR activation using ELISA, immunoblot, and immunoprecipitation techniques, and for proliferation using cell counting after stimulation with CXCL12 or vehicle. Results The results of these studies identify CXCL12 as a novel inducer of amphiregulin ectodomain shedding and show that both basal and CXCL12-mediated amphiregulin shedding are ADAM10- and Src kinase-dependent in non-transformed N15C6 cells. In contrast, amphiregulin shedding is not amplified subsequent to stimulation with exogenous CXCL12, and is not reduced subsequent to metalloprotease- or Src kinase-inhibition, in highly aggressive PC3 prostate cancer cells. These data also show that CXCL12-mediated cellular proliferation requires EGFR transactivation in a Src-and ADAM-dependent manner in non-transformed prostate epithelial cells. However, these same mechanisms are dysfunctional in highly transformed prostate cancer cells, which secrete amphiregulin in an autocrine manner that cannot be repressed through metalloprotease- or Src kinase inhibition. Conclusion These findings show that non-transformed and transformed

  5. Evaluation of ADAM/1 model for advanced coal extraction concepts

    NASA Technical Reports Server (NTRS)

    Deshpande, G. K.; Gangal, M. D.

    1982-01-01

    Several existing computer programs for estimating life cycle cost of mining systems were evaluated. A commercially available program, ADAM/1 was found to be satisfactory in relation to the needs of the advanced coal extraction project. Two test cases were run to confirm the ability of the program to handle nonconventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs.

  6. ADAMS GAP AND SHINBONE CREEK ROADLESS AREAS, ALABAMA.

    USGS Publications Warehouse

    Klein, T.L.; Harrison, Donald K.

    1984-01-01

    The Adams Gap and Shinbone Creek Roadless Areas in Alabama were evaluated for their mineral potential. The only resource within the established boundary of the roadless area is quartzite suitable for crushed rock or refractory-grade aggregate. The quartzite contains deleterious impurities and is found in abundance outside the areas. Natural gas or petroleum may exist at depth. Detailed seismic studies and deep drilling tests are needed before a reasonable estimate of hydrocarbon potential can be made.

  7. iRhoms 1 and 2 are essential upstream regulators of ADAM17-dependent EGFR signaling

    PubMed Central

    Li, Xue; Maretzky, Thorsten; Weskamp, Gisela; Monette, Sébastien; Qing, Xiaoping; Issuree, Priya Darshinee A.; Crawford, Howard C.; McIlwain, David R.; Mak, Tak W.; Salmon, Jane E.; Blobel, Carl P.

    2015-01-01

    The metalloproteinase ADAM17 (a disintegrin and metalloprotease 17) controls EGF receptor (EGFR) signaling by liberating EGFR ligands from their membrane anchor. Consequently, a patient lacking ADAM17 has skin and intestinal barrier defects that are likely caused by lack of EGFR signaling, and Adam17−/− mice die perinatally with open eyes, like Egfr−/− mice. A hallmark feature of ADAM17-dependent EGFR ligand shedding is that it can be rapidly and posttranslationally activated in a manner that requires its transmembrane domain but not its cytoplasmic domain. This suggests that ADAM17 is regulated by other integral membrane proteins, although much remains to be learned about the underlying mechanism. Recently, inactive Rhomboid 2 (iRhom2), which has seven transmembrane domains, emerged as a molecule that controls the maturation and function of ADAM17 in myeloid cells. However, iRhom2−/− mice appear normal, raising questions about how ADAM17 is regulated in other tissues. Here we report that iRhom1/2−/− double knockout mice resemble Adam17−/− and Egfr−/− mice in that they die perinatally with open eyes, misshapen heart valves, and growth plate defects. Mechanistically, we show lack of mature ADAM17 and strongly reduced EGFR phosphorylation in iRhom1/2−/− tissues. Finally, we demonstrate that iRhom1 is not essential for mouse development but regulates ADAM17 maturation in the brain, except in microglia, where ADAM17 is controlled by iRhom2. These results provide genetic, cell biological, and biochemical evidence that a principal function of iRhoms1/2 during mouse development is to regulate ADAM17-dependent EGFR signaling, suggesting that iRhoms1/2 could emerge as novel targets for treatment of ADAM17/EGFR-dependent pathologies. PMID:25918388

  8. The alpha secretase ADAM10: A metalloprotease with multiple functions in the brain.

    PubMed

    Saftig, Paul; Lichtenthaler, Stefan F

    2015-12-01

    Proteins belonging to the 'A Disintegrin And Metalloproteinase' (ADAM) family are membrane-anchored proteases that are able to cleave the extracellular domains of several membrane-bound proteins in a process known as 'ectodomain shedding'. In the central nervous system, ADAM10 has attracted the most attention, since it was described as the amyloid precursor protein α-secretase over ten years ago. Despite the excitement over the potential of ADAM10 as a novel drug target in Alzheimer disease, the physiological functions of ADAM10 in the brain are not yet well understood. This is largely because of the embryonic lethality of ADAM10-deficient mice, which results from the loss of cleavage and signaling of the Notch receptor, another ADAM10 substrate. However, the recent generation of conditional ADAM10-deficient mice and the identification of further ADAM10 substrates in the brain has revealed surprisingly numerous and fundamental functions of ADAM10 in the development of the embryonic brain and also in the homeostasis of adult neuronal networks. Mechanistically, ADAM10 controls these functions by utilizing unique postsynaptic substrates in the central nervous system, in particular synaptic cell adhesion molecules, such as neuroligin-1, N-cadherin, NCAM, Ephrin A2 and A5. Consequently, a dysregulation of ADAM10 activity is linked to psychiatric and neurological diseases, such as epilepsy, fragile X syndrome and Huntington disease. This review highlights the recent progress in understanding the substrates and function as well as the regulation and cell biology of ADAM10 in the central nervous system and discusses the value of ADAM10 as a drug target in brain diseases.

  9. 1988 Horton Medal presented to Peter S. Eagleson

    NASA Astrophysics Data System (ADS)

    Rodriguez-Iturbe, Ignacio; Eagleson, Peter S.

    It is indeed a great honor for me, and also a great pleasure, to present to you the 1988 recipient of the Robert E. Horton Medal, Peter S. Eagleson. Shortly after it became public that Pete was the winner of this year's medal, I commented to my wife that, although I had never given a citation for an AGU medalist, this was one I would really love to give. The reason is simple: there is no one in the world who better represents the standards of excellence that a hydrologist hopes to achieve and that hydrologists hope our discipline will attain than Peter Eagleson.Pete did not start his research career in hydrology. In fact, his Ph.D. thesis in 1956 and his research up to 1965 were mainly in the field of sediment sorting and transport by waves on beaches. During this period he also investigated problems related to flow-induced vibrations of plates. His research in these areas was extremely successful, producing three chapters in books and about 20 journal papers in addition to many technical reports and journal discussions. Indeed, Pete had made his mark in wave theory and sediment transport, but it was good fortune for our field that starting about 1964 his interest in hydrology overcame all his past experience and assured a reputation in the waves and sediment field, and thus he embarked on a new adventure—bringing into hydrology the scientific rigor that existed in more academically established disciplines. With his strong fluid mechanics background—he still teaches that subject to undergraduates at MIT—Pete was ideally suited to lead the field toward new problems and also toward new approaches to old problems . . . and this he did indeed! Just in 1967 he and his students published six papers, most of them in Water Resources Research, which had a strong, an almost immediate impact on the field of hydrology. Here was somebody who was tackling the modeling of overland flow with the scientific standards of fluid mechanics. At the same time, finally somebody had

  10. Riccardo Giacconi to Receive National Medal of Science

    NASA Astrophysics Data System (ADS)

    2005-02-01

    Riccardo Giacconi, very recently retired President of Associated Universities, Inc. (AUI), will be awarded the National Medal of Science by President George W. Bush on March 14, according to the White House. Giacconi, who received the Nobel Prize in Physics in 2002, will be honored for his pioneering research in X-ray astronomy and for his visionary leadership of major astronomy facilities. Established by Congress in 1959, the National Medal of Science is the Nation's highest honor for American scientists and is awarded annually by the President of the United States to individuals "deserving of special recognition for their outstanding contributions to knowledge." "We are extremely proud that Riccardo Giacconi has been selected to receive the nation's highest award for scientific achievement," said current AUI President Ethan J. Schreier, a long-term colleague of Dr. Giacconi. "It is another fitting recognition for an outstanding scientific career that has enhanced our basic understanding of the universe," Schreier added. Giacconi, known as the father of X-ray astronomy, used X-ray detectors launched on rockets to discover the first cosmic X-ray source in 1962. Because X-ray radiation is absorbed in Earth's atmosphere, space-based instruments are necessary to study it. Giacconi outlined a methodical program to investigate this new X-ray universe and, working with his research group at American Science and Engineering, Inc. in Cambridge, Massachusetts, developed the first space satellite dedicated to the new field of X-ray astronomy. Named Uhuru, this X-ray satellite observatory was launched in 1970 and subsequently discovered hundreds of X-ray sources. The ground-breaking work of Giacconi and his group led to the discovery of black holes, which to that point had been hypothesized but never seen. Giacconi was also the first to prove that the universe contains background radiation of X-ray light. Riccardo Giacconi has played a key role in many other landmark

  11. Emergency department visits during an Olympic gold medal television broadcast

    PubMed Central

    Redelmeier, Donald A; Vermeulen, Marian J

    2011-01-01

    Background Practice pattern variations are often attributed to physician decision-making with no accounting for patient preferences. Objective To test whether a mass media television broadcast unrelated to health was associated with changes in the rate and characteristics of visits for acute emergency care. Design Time-series analysis of emergency department visits for any reason. Subjects Population-based sample of all patients seeking emergency care in Ontario, Canada. Measures The broadcast day was defined as the Olympic men’s gold medal ice hockey game final. The control days were defined as the 6 Sundays before and after the broadcast day. Results A total of 99 447 visits occurred over the 7 Sundays, of which 13 990 occurred on the broadcast day. Comparing the broadcast day with control days, we found no significant difference in the hourly rate of visits before the broadcast (544 vs 537, p = 0.41) or after the broadcast (647 vs 639, p = 0.55). In contrast, we observed a significant reduction in hourly rate of visits during the broadcast (647 vs 783, p < 0.001), equal to an absolute decrease of 409 patients, a relative decrease of 17% (95% confidence interval 13–21), or about 136 fewer patients per hour. The relative decrease during the broadcast was particularly large for adult men with low triage severity. The greatest reductions were for patients with abdominal, musculoskeletal or traumatic disorders. Conclusion Mass media television broadcasts can influence patient preferences and thereby lead to a decrease in emergency department visits. PMID:21915235

  12. Revisiting "The strengths of pharmacy": the 1953 Remington Medal address.

    PubMed

    Oddis, J A

    1990-09-01

    Five reasons for the continued strength of the pharmacy profession, each of which was originally proposed in 1953 by Hugh Muldoon, are explored in this address by 1990 Remington Medalist Joseph A. Oddis. The strengths of pharmacy in the 1990s are based on the same factors that served the profession well in the 1950s. As outlined in Muldoon's 1953 Remington Medal address, these factors are (1) pharmacists' character and motivation, (2) the profession's public trust, (3) the profession's respect for education, (4) pharmacy's willingness to confront its problems, and (5) pharmacy's concern for the future. Today's pharmacists are strongly motivated; they continue to strive to raise the level of services provided in all practice settings and to maximize their value to patients. Pharmacists retain a high degree of public trust; they should take advantage of this position to expand their scope of services in areas such as managed care. During the 1990s pharmacy's concern for education is focused on pharmacy work force needs as a whole, including issues related to technical personnel and specialization as well as the role of the Pharm.D. degree in the overall education program. Pharmacy's willingness to resolve its problems is evident in the growth of such organizations as the Joint Commission of Pharmacy Practitioners, which has allowed the profession to achieve strength through unity. Pharmacy's concern for the future is reflected in the deliberations at recent conferences on Pharmacy in the 21st Century, where participants concurred that pharmacy's highest priority is to demonstrate and communicate to others its value in health care.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Localization of α-adrenoceptors: JR Vane Medal Lecture

    PubMed Central

    McGrath, John C

    2015-01-01

    This review is based on the JR Vane Medal Lecture presented at the BPS Winter Meeting in December 2011 by J.C. McGrath. A recording of the lecture is included as supporting information. It covers his laboratory's work from 1990 to 2010 on the localization of vascular α1-adrenoceptors in native tissues, mainly arteries. Main points: (i) α1-adrenoceptors are present on several cell types in arteries, not only on medial smooth muscle, but also on adventitial, endothelial and nerve cells; (ii) all three receptor subtypes (α1A, α1B, α1D) are capable of binding ligands at the cell surface, strongly indicating that they are capable of function and not merely expressed. (iii) all of these cell types can take up an antagonist ligand into the intracellular compartments to which endocytosing receptors move; (iv) each individual subtype can exist at the cell surface and intracellularly in the absence of the other subtypes. As functional pharmacological experiments show variations in the involvement of the different subtypes in contractions of different arteries, it is concluded that the presence and disposition of α1-adrenoceptors in arteries is not a simple guide to their involvement in function. Similar locations of the subtypes, even in different cell types, suggest that differences between the distribution of subtypes in model systems do not directly correlate with those in native tissues. This review includes a historical summary of the alternative terms used for adrenoceptors (adrenergic receptors, adrenoreceptors) and the author's views on the use of colours to illustrate different items, given his partial colour-blindness. PMID:25377869

  14. Dr. Lytle Adams' incendiary "bat bomb" of World War II.

    PubMed

    Christen, Arden G; Christen, Joan A

    2004-11-01

    On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place. PMID:15666497

  15. Dr. Lytle Adams' incendiary "bat bomb" of World War II.

    PubMed

    Christen, Arden G; Christen, Joan A

    2004-11-01

    On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place.

  16. An Examination of Newbery Medal Books from the 1920s through the 2000s: Biblical Perspective

    ERIC Educational Resources Information Center

    Fleming, Kimberly

    2012-01-01

    Content analysis was conducted to determine the frequency of the presence of positive Biblical virtues and paired opposite traits across 18 Newbery Medal books from the 1920s through the 2000s because the Newbery Award is a prestigious honor bestowed upon children's literature, and the criteria for selection among books specifically precludes…

  17. The Newbery and Caldecott Awards: A Guide to the Medal and Honor Books. 2000 Edition.

    ERIC Educational Resources Information Center

    2000

    Each year the Newbery and Caldecott Medals are awarded by the American Library Association for the most distinguished American children's books published the previous year. With its annotations for all winning titles and honor books since the inception of the awards (Newbery in 1922 to be awarded annually to the author of the most distinguished…

  18. Milton M. Holland: Panola County Recipient of the Medal of Honor.

    ERIC Educational Resources Information Center

    Johnson, Jennifer, Ed.

    1992-01-01

    This publication features an article about Milton M. Holland, a black American from East Texas, who is credited with being the first black Texan to have won the Congressional Medal of Honor during the U.S. Civil War. The articles in the issue concern Milton Holland and other black Americans who served in the Civil War. The articles include:…

  19. 31 CFR 92.2 - Sale of “list” medals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 31 Money and Finance: Treasury 1 2013-07-01 2013-07-01 false Sale of âlistâ medals. 92.2 Section 92.2 Money and Finance: Treasury Regulations Relating to Money and Finance MONETARY OFFICES... sufficient to cover their cost, and to include mailing cost when mailed. Copies of the list of...

  20. Kroll, Murakami, and Seneviratne Receive 2013 James B. Macelwane Medals: Response

    NASA Astrophysics Data System (ADS)

    Murakami, Motohiko

    2014-01-01

    Thank you very much, Jay, for your generous citation and for all of your support. It is a great honor for me to receive this medal. First, I sincerely thank AGU for this recognition and my nominators for their support and time.

  1. Andreas Vesalius and the Occo medals of Augsburg. Evidence of a professional friendship.

    PubMed

    Houtzager, H L

    2000-06-01

    The friendly connection that existed between Andreas Vesalius (1514-1564) and his learned friends in Augsburg comprised three periods in the life of the emperor's court physician. The close ties that must have connected Adolphus Occo II and III and Vesalius are expressed in a number of medals carrying their images. PMID:11624585

  2. 14 CFR 1221.201 - Basis for award of the medal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... be awarded to any person who is or has been designated to travel in space and who has distinguished... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Basis for award of the medal. 1221.201 Section 1221.201 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL...

  3. Gold Medal Award for Life Achievement in the Application of Psychology: Edwin A. Fleishman

    ERIC Educational Resources Information Center

    American Psychologist, 2004

    2004-01-01

    The 2004 Gold Medal Award for Life Achievement in the Application of Psychology was awarded to Edwin A. Fleishman, for his significant contributions to the science and applications of psychology, which he has sustained over his remarkable career. He is cited for his research, which has had a profound influence on our understanding of human…

  4. Benjamin Franklin's Commemorative Medal "Libertas Americana": A Study in Rhetorical Iconology.

    ERIC Educational Resources Information Center

    Olson, Lester C.

    1990-01-01

    Investigates the underlying rhetorical functions of how Benjamin Franklin used the medal to praise the national characters of France and the United States in those two countries, while he also used it to influence government policy in Malta and to vindicate himself from criticism in England. (KEH)

  5. 78 FR 25476 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-01

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Office of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Bureau of Justice Assistance (BJA), Department of Justice. ACTION: Notice of meeting. SUMMARY: This is...

  6. 77 FR 26790 - Meeting of the Public Safety Officer Medal of Valor Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Office of Justice Programs Meeting of the Public Safety Officer Medal of Valor Review Board AGENCY: Office of Justice Programs (OJP), Bureau of Justice Assistance (BJA), Department of Justice. ACTION:...

  7. Gold Medal Award for Life Achievement in the Practice of Psychology: Arthur L. Kovacs.

    ERIC Educational Resources Information Center

    American Psychologist, 2004

    2004-01-01

    The 2004 Gold Medal Award for Life Achievement in the Practice of Psychology is awarded to Arthur L. Kovacs. He is recognized for making outstanding contributions to achieving statutory recognition and securing insurance reimbursement, and as a pioneer in the professional school movement, having trained several generations of practitioners.

  8. Gold Medal Award for Life Achievement in Psychology in the Public Interest

    ERIC Educational Resources Information Center

    American Psychologist, 2004

    2004-01-01

    The 2004 Gold Medal Award for Life Achievement in Psychology in the Public Interest is awarded to Florence L. Denmark. She is recognized for her efforts to help legitimize the psychology of women by teaching the first doctoral psychology course in the field and through her scholarly texts and articles. She continues to have an impact on the…

  9. Gold Medal Award for Life Achievement in the Science of Psychology: Janet Taylor Spence.

    ERIC Educational Resources Information Center

    American Psychologist, 2004

    2004-01-01

    The 2004 Gold Medal Award for Life Achievement in the Science of Psychology is awarded to Janet Taylor Spence. She is recognized for her outstanding scientific contributions that have had a profound theoretical and empirical impact on two areas of inquiry: Her early seminal research on the motivational properties of trait anxiety led the way to…

  10. 14 CFR 1221.201 - Basis for award of the medal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... be awarded to any person who is or has been designated to travel in space and who has distinguished... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Basis for award of the medal. 1221.201 Section 1221.201 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL...

  11. 14 CFR § 1221.201 - Basis for award of the medal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... be awarded to any person who is or has been designated to travel in space and who has distinguished... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Basis for award of the medal. § 1221.201 Section § 1221.201 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION THE NASA SEAL...

  12. Discourse following award of Kepler Gold Medal. [Kepler Laws, planetary astronomy and physics, and Jupiter studies

    NASA Technical Reports Server (NTRS)

    Kuiper, G. P.

    1973-01-01

    Kuiper briefly reviews Kepler's contributions to the field of planetary astronomy and physics, along with references to his own background in the study of stars, planets, and the solar system. He mentions his participation in NASA programs related to planetary astronomy. He concludes his remarks with thanks for being honored by the award of the Kepler Gold Medal.

  13. Andreas Vesalius and the Occo medals of Augsburg. Evidence of a professional friendship.

    PubMed

    Houtzager, H L

    2000-06-01

    The friendly connection that existed between Andreas Vesalius (1514-1564) and his learned friends in Augsburg comprised three periods in the life of the emperor's court physician. The close ties that must have connected Adolphus Occo II and III and Vesalius are expressed in a number of medals carrying their images.

  14. 76 FR 36176 - Pricing for National September 11 Memorial & Museum Commemorative Medal

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY United States Mint Pricing for National September 11 Memorial & Museum Commemorative Medal ACTION: Notice. SUMMARY: The United States Mint is announcing the price of the National September 11 Memorial &...

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

    PubMed

    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.

  16. ADAM22, A KV1 CHANNEL INTERACTING PROTEIN, RECRUITS MAGUKS TO JUXTAPARANODES OF MYELINATED AXONS

    PubMed Central

    Ogawa, Yasuhiro; Oses-Prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L.; Trimmer, James S.; Meijer, Dies; Rasband, Matthew N.

    2009-01-01

    Clustered Kv1 K+ channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments (AIS), and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 α subunits, then used mass-spectrometry to identify interacting proteins. We found that ADAM22 (A Disintegrin And Metalloproteinase 22) is a component of the Kv1 channel complex, and that ADAM22 co-immunoprecipitates Kv1.2 and the MAGUKs PSD-93 and PSD-95. When co-expressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, co-expression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis of Caspr-null mice showed that like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis of Caspr2-, PSD-93-, PSD-95-, and double PSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis of ADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K+ channel complex that recruits MAGUKs to juxtaparanodes. PMID:20089912

  17. Development of heterogeneous olympic medal metal nanoparticle catalysts for environmentally benign molecular transformations based on the surface properties of hydrotalcite.

    PubMed

    Kaneda, Kiyotomi; Mitsudome, Takato; Mizugaki, Tomoo; Jitsukawa, Koichiro

    2010-12-08

    In this review, we describe the development by our research group of highly functionalized heterogeneous Olympic medal metal (gold, silver, and copper) nanoparticle catalysts using hydrotalcite as a support, aimed towards Green and Sustainable Chemistry. Olympic medal metal nanoparticles can cooperate with the basic sites on the hydrotalcite surface, providing unique and high performance catalysis in environmentally-benign organic transformations such as aerobic oxidation of alcohols, lactonization of diols and selective deoxygenation of epoxides and nitro aromatic compounds.

  18. [Cloning of mouse adam10 gene promoter and construction and identification of dual luciferase reporter system].

    PubMed

    Chen, Wei; Chen, Chong; Zhang, Huan-Xin; Cao, Jiang; Sang, Wei; Wu, Qing-Yun; Zhao, Kai; Zang, Yu; Zeng, Ling-Yu; Xu, Kai-Lin

    2012-06-01

    This study was aimed to clone mouse adam10 gene promoter and construct its dual luciferase report vector, and to investigate its transcriptional activity. Total DNA was extracted from mouse brain and used for amplifying the fragment containing adam10 gene promoter by PCR. The amplified product was inserted into pGL-4.10 vector to construct pGL4.10-adam10. The pGL4.10-adam10 and control plasmid pGL4.74 were co-transfected into HEK293 FT cells by lipofectamine 2000. The activity of adam10 gene promoter was assayed by luciferase system. The results showed that the recombinant plasmid pGL4.10-adam10 containing promoter of mouse adam10 was correctly constructed. The method was optimized by changing ratio of two plasmids. Moreover, the transcriptional activity of pGL4.10-adam10 stimulated by ionomycin increased. It is concluded that the dual luciferase reporter system is successfully established, which is useful in bioluminescence imaging technology in vitro. The effect of ionomycin can enhance the transcriptional activity of adam10 gene promoter.

  19. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development.

    PubMed

    Kwon, Jeongwoo; Jeong, Sung-min; Choi, Inchul; Kim, Nam-Hyung

    2016-01-01

    ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development. PMID:27043020

  20. ADAM10 Is Involved in Cell Junction Assembly in Early Porcine Embryo Development

    PubMed Central

    Kwon, Jeongwoo; Jeong, Sung-min; Choi, Inchul; Kim, Nam-Hyung

    2016-01-01

    ADAM10 (A Disintegrin and Metalloprotease domain-containing protein 10) is a cell surface protein with a unique structure possessing both potential adhesion and protease domains. However, the role of ADAM10 in preimplantation stage embryos is not clear. In this study, we examined the expression patterns and functional roles of ADAM10 in porcine parthenotes during preimplantation development. The transcription level of ADAM10 dramatically increased from the morula stage onward. Immunostaining revealed that ADAM10 was present in both the nucleus and cytoplasm in early cleavage stage embryos, and localized to the apical region of the outer cells in morula and blastocyst embryos. Knockdown (KD) of ADAM10 using double strand RNA did not alter preimplantation embryo development until morula stage, but resulted in significantly reduced development to blastocyst stage. Moreover, the KD blastocyst showed a decrease in gene expression of adherens and tight junction (AJ/TJ), and an increase in trophectoderm TJ permeability by disrupting TJ assembly. Treatment with an ADAM10 specific chemical inhibitor, GI254023X, at the morula stage also inhibited blastocyst development and led to disruption of TJ assembly. An in situ proximity ligation assay demonstrated direct interaction of ADAM10 with coxsackie virus and adenovirus receptor (CXADR), supporting the involvement of ADAM10 in TJ assembly. In conclusion, our findings strongly suggest that ADADM10 is important for blastocyst formation rather than compaction, particularly for TJ assembly and stabilization in preimplantation porcine parthenogenetic development. PMID:27043020

  1. From evaporating pans to transpiring plants (John Dalton Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Roderick, Michael

    2013-04-01

    observations that win. That is the basis of science. In this Dalton Medal lecture we first examine pan evaporation observations and show why pan evaporation has declined. Armed with that knowledge we then investigate the consequences for plant water use and how this is directly coupled to the catchment water balance.

  2. Recent eruptions of Mount Adams, Washington Cascades, USA

    USGS Publications Warehouse

    Hildreth, Wes; Fierstein, Judy

    1997-01-01

    The postglacial eruption rate for the Mount Adams volcanic field is ∼0.1 km3/k.y., four to seven times smaller than the average rate for the past 520 k.y. Ten vents have been active since the last main deglaciation ∼15 ka. Seven high flank vents (at 2100-2600 m) and the central summit vent of the 3742-m stratocone produced varied andesites, and two peripheral vents (at 2100 and 1200 m) produced mildly alkalic basalt. Eruptive ages of most of these units are bracketed with respect to regional tephra layers from Mount Mazama and Mount St. Helens. The basaltic lavas and scoria cones north and south of Mount Adams and a 13-km-long andesitic lava flow on its east flank are of early postglacial age. The three most extensive andesitic lava-flow complexes were emplaced in the mid-Holocene (7-4 ka). Ages of three smaller Holocene andesite units are less well constrained. A phreatomagmatic ejecta cone and associated andesite lavas that together cap the summit may be of latest Pleistocene age. but a thin layer of mid-Holocene tephra appears to have erupted there as well. An alpine-meadow section on the southeast flank contains 24 locally derived Holocene andesitic ash layers intercalated with several silicic tephras from Mazama and St. Helens. Microprobe analyses of phenocrysts from the ash layers and postglacial lavas suggest a few correlations and refine some age constraints. Approximately 6 ka, a 0.07-km3 debris avalanche from the southwest face of Mount Adams gen-erated a clay-rich debris flow that devastated >30 km2 south of the volcano. A gravitationally metastable 2-to 3-km3 reservoir of hydrothermally altered fragmental andesite remains on the ice-capped summit and, towering 3 km above the surrounding lowlands, represents a greater hazard than an eruptive recurrence in the style of the last 15 k.y.

  3. Simulation of Naval Guns' Breechblock System Dynamics Based on ADAMS

    NASA Astrophysics Data System (ADS)

    Tan, Bo; Liu, Hui-Min; Liu, Kai

    In order to study the dynamical characteristics of the breechblock system during gun firing, a virtual prototype model was established based on ADAMS, in which motion and force transmission among mechanisms are realized by collision. By simulation, kinematics and dynamics properties of main components are obtained, and the relationships between the motion of breechblock and the position of breechblock opening plate are analyzed. According to the simulation results, the collision among the breechblock opening plate and the roller is discontinuous, which may make the breechblock system fail to hitch the breechblock reliably. And within allowable scope of the structure, the breechblock opening template should be installed near the upside as much as possible.

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

    PubMed Central

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

    2016-01-01

    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. The "delivery" of Adam: a medical interpretation of Michelangelo.

    PubMed

    Di Bella, Stefano; Taglietti, Fabrizio; Iacobuzio, Andrea; Johnson, Emma; Baiocchini, Andrea; Petrosillo, Nicola

    2015-04-01

    This article describes what we believe to be the key to interpreting the concept represented by Michelangelo's painting the Creation of Adam. This fresco, one of his most famous masterpieces, is situated in the heart of the Sistine Chapel and is viewed by millions of people every year. A man of many talents, Michelangelo's proficiency in anatomical dissection is reflected in his artwork. As such, analyses of hidden meanings in this fresco have been ascribed, including the concept of the "Brain-God." However, we see a postpartum uterus and adjacent anatomy, justifying our interpretation that Michelangelo was depicting something far more fundamental: the birth of mankind. PMID:25841253

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

    PubMed

    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. PMID:27688633

  7. ADAM15 Is Functionally Associated with the Metastatic Progression of Human Bladder Cancer

    PubMed Central

    Rubin, John R.; Hayward, Alexandra; Cates, Angelica L.; Day, Kathleen C.; El-Sawy, Layla; Kunju, L. Priya; Daignault, Stephanie; Lee, Cheryl T.; Liebert, Monica; Hussain, Maha; Day, Mark L.

    2016-01-01

    ADAM15 is a member of a family of catalytically active disintegrin membrane metalloproteinases that function as molecular signaling switches, shed membrane bound growth factors and/or cleave and inactivate cell adhesion molecules. Aberrant metalloproteinase function of ADAM15 may contribute to tumor progression through the release of growth factors or disruption of cell adhesion. In this study, we utilized human bladder cancer tissues and cell lines to evaluate the expression and function of ADAM15 in the progression of human bladder cancer. Examination of genome and transcriptome databases revealed that ADAM15 ranked in the top 5% of amplified genes and its mRNA was significantly overexpressed in invasive and metastatic bladder cancer compared to noninvasive disease. Immunostaining of a bladder tumor tissue array designed to evaluate disease progression revealed increased ADAM15 immunoreactivity associated with increasing cancer stage and exhibited significantly stronger staining in metastatic samples. About half of the invasive tumors and the majority of the metastatic cases exhibited high ADAM15 staining index, while all low grade and noninvasive cases exhibited negative or low staining. The knockdown of ADAM15 mRNA expression significantly inhibited bladder tumor cell migration and reduced the invasive capacity of bladder tumor cells through MatrigelTM and monolayers of vascular endothelium. The knockdown of ADAM15 in a human xenograft model of bladder cancer inhibited tumor growth by 45% compared to controls. Structural modeling of the catalytic domain led to the design of a novel ADAM15-specific sulfonamide inhibitor that demonstrated bioactivity and significantly reduced the viability of bladder cancer cells in vitro and in human bladder cancer xenografts. Taken together, the results revealed an undescribed role of ADAM15 in the invasion of human bladder cancer and suggested that the ADAM15 catalytic domain may represent a viable therapeutic target in

  8. 77 FR 75207 - The Adams Express Company and Petroleum & Resources Corporation; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... COMMISSION The Adams Express Company and Petroleum & Resources Corporation; Notice of Application December 13... and Petroleum & Resources Corporation (the ``Funds''). DATES: Filing Dates: The application was filed..., 2012, The Adams Express Company held approximately 8.5% of the outstanding shares of...

  9. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development. PMID:27333034

  10. ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease.

    PubMed

    Letronne, Florent; Laumet, Geoffroy; Ayral, Anne-Marie; Chapuis, Julien; Demiautte, Florie; Laga, Mathias; Vandenberghe, Michel E; Malmanche, Nicolas; Leroux, Florence; Eysert, Fanny; Sottejeau, Yoann; Chami, Linda; Flaig, Amandine; Bauer, Charlotte; Dourlen, Pierre; Lesaffre, Marie; Delay, Charlotte; Huot, Ludovic; Dumont, Julie; Werkmeister, Elisabeth; Lafont, Franck; Mendes, Tiago; Hansmannel, Franck; Dermaut, Bart; Deprez, Benoit; Hérard, Anne-Sophie; Dhenain, Marc; Souedet, Nicolas; Pasquier, Florence; Tulasne, David; Berr, Claudine; Hauw, Jean-Jacques; Lemoine, Yves; Amouyel, Philippe; Mann, David; Déprez, Rebecca; Checler, Frédéric; Hot, David; Delzescaux, Thierry; Gevaert, Kris; Lambert, Jean-Charles

    2016-07-01

    Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30(mut)) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development.

  11. African American Faculty at Traditionally White Institutions: The Impact of the "Adams" Case on Hiring Practices.

    ERIC Educational Resources Information Center

    Silver, Joseph H., Sr.

    1990-01-01

    The "Adams v. Richardson" case required states to redress inequalities in employment opportunities for African American faculty at traditionally White institutions (TWIs). Studies the impact of the litigation in nine states affected by "Adams" and finds evidence of some positive effect. Calls for greater court oversight of TWI faculty hiring. (AF)

  12. DEVELOPMENT OF THE HUMAN LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHEMETRY (ADAM).

    EPA Science Inventory

    We measured, in vivo, the airspace calibers of the small airways and alveoli by ADAM in the lungs of children of ages 6 to 18 years and adults aged 18 to 80 years. ADAM utilizes the gravitational settling time of inhaled monodisperse particles to infer the vertical distance to th...

  13. 75 FR 51519 - Regional Transportation District-Acquisition Exemption-Union Pacific Railroad Company in Adams...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... Railroad Company in Adams, Denver, and Jefferson Counties, CO Regional Transportation District (RTD) \\1... Subdivision extending approximately 8.96 miles, from milepost 628.50, in Adams County, CO., to milepost 637.46... operations as a result of this transaction will not result in the creation of a Class II or Class I...

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Acceptance of the 2009 Henry Baldwin Ward Medal: The accidental parasitologist

    USGS Publications Warehouse

    Lafferty, Kevin D.

    2009-01-01

    Members of the Society, President Conn, colleagues, friends, and particularly students, the Ward Medal recipient, from Clarke Read onward, traditionally recounts how their career was shaped. A decade ago, in a crumbling Kona hotel, the ASP's own tattooed lady, Janine Caira, opened her Ward Medal address with: “To all future Ward Medalists, many of whom I trust are sitting in the audience out there today, I say: savor the moment! You have no idea how much easier it is to be sitting out there where you are than standing up here where I am” (Caira 1998). I certainly didn't imagine that Janine was delivering her advice to me and it is presumptuous to imagine my story is a template for shaping a career. As the title of my talk indicates, it was an accident.

  16. From Abrupt Change to the Future (Hans Oeschger Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Stocker, T.

    2009-04-01

    The award of the Oeschger Medal 2009 is a particular honor and pleasure for me as I was given the chance to take over from Hans Oeschger the lead of a wonderful Institute at the University of Bern in 1993. Very apprehensive first, in front of the huge expectations and challenges, I quickly found dear colleagues, close collaborators and extremely supportive staff who all dedicated their time and creativity to work for the common goal of better understanding the Earth System, its variations in the past and its sensitivity to perturbations that man is inflicting on it today. Although met with innate skepticism first by the experimental physicists, our efforts in modelling, particularly the approach of using climate models of reduced complexity, quickly paid off and provided added value to the hard won data and measurements from polar ice cores. It is clear that modelling in such a diverse environment is so much more stimulating and enriching than working on a sophisticated parameterisation in a big modelling centre. Simple models have suggested that the Earth System may have limited stability and that rather fundamental changes could be triggered by the increase of greenhouse gases. However, it is the unique results from polar ice cores, particularly from Greenland that showed that, indeed, the Earth System has limited stability and can react in extremely abrupt ways to changes in forcing. Likewise, the Antarctic ice cores have provided one of the corner stones of our knowledge about climate change: Concentrations of CO2 are today 29% higher than ever during the last 800,000 years. These two fundamental insights from the paleoclimatic archive call for accelerated research into the sensitivity of the climate system and its components to perturbations, as well as the investigation of feedback mechanisms in the biogeochemical cycles that are disturbed by the input of CO2 into the atmosphere by burning fossil fuels and land use change. Our research has only scratched the

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

    PubMed

    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 < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased 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

  18. Kroll, Murakami, and Seneviratne Receive 2013 James B. Macelwane Medals: Citation for Motohiko Murakami

    NASA Astrophysics Data System (ADS)

    Bass, Jay

    2014-01-01

    The James B. Macelwane Medal of AGU is presented to Motohiko Murakami for his discovery of the postperovskite phase of MgSiO3, for a new class of sound velocity measurements under lower mantle pressure-temperature conditions that have changed our view of whole-Earth chemistry, and for other fundamental contributions that have furthered our understanding of the Earth's deep interior.

  19. The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells

    SciTech Connect

    Schramme, Anja; Abdel-Bakky, Mohamed Sadek; Kaempfer-Kolb, Nicole; Pfeilschifter, Josef

    2008-05-30

    In this study, we analyzed the regulation and functional role of CXCL16 in human mesangial cells (hMCs). We can show, that CXCL16 is constitutively expressed in hMCs and is further up-regulated by cytokine mix (IFN{gamma}, TNF{alpha}, and IL1{beta}). The constitutive release of CXCL16 from hMCs was rapidly induced by the stimulation with cytokines. We identified ADAM10 and ADAM17 as being responsible for the cytokine-induced shedding of CXCL16. Notably, targeting ADAM10 and ADAM17 in hMCs decreased the chemotaxis of T-Jurkat cells, whereas the inhibition of CXCL16 had no significant influence. This suggests that both proteases are important players in the recruitment of immune cells into the glomerulus, but other substrates than CXCL16 are involved in this process. Finally, we could show that the inhibition of CXCL16, ADAM10, and ADAM17 led to a strong reduction of cell proliferation and migration of hMCs. This finding could be important to develop novel diagnostic and therapeutic strategies to treat mesangial proliferative kidney diseases.

  20. Gold Medal Award for life achievement in psychology in the public interest.

    PubMed

    2012-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2011 recipient of the Gold Medal Award for Life Achievement in Psychology in the Public Interest is Salvatore R. Maddi. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 120th Annual Convention of the American Psychological Association on August 3, 2012, at 4:00 p.m. Members of the 2012 APF Board of Trustees are Dorothy W. Cantor, president; Charles L. Brewer, vice president/secretary; Gerald Koocher, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; Brian N. Baird; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Connie Chan; William Howell; Anthony Jackson; Ronald F. Levant; Aurelio Prifitera; Sandra Shullman; Archie L. Turner; and Kurt Geisinger, APA Board of Directors liaison.

  1. Gold medal award for life achievement in the practice of psychology.

    PubMed

    2009-01-01

    The American Psychological Foundation (APF) Gold Medal Awards recognize distinguished and enduring records of accomplishment in four areas of psychology: the application of psychology, the practice of psychology, psychology in the public interest, and the science of psychology. The 2009 recipient of the Gold Medal Award for Life Achievement in the Practice of Psychology is Robert J. Resnick, PhD, ABPP. Dorothy W. Cantor, president of the APF, will present the APF Gold Medal Awards at the 117th Annual Convention of the American Psychological Association on August 7, 2009, at 4:00 p.m. Members of the 2009 APF Board of Trustees are Dorothy W. Cantor, president; William Howell, vice president/secretary; Archie L. Turner, treasurer; Elisabeth R. Straus, executive vice president/executive director; Norman Anderson; David H. Barlow; Camilla Benbow; Sharon Stephens Brehm; Charles L. Brewer; Anthony Jackson; Steven E. James; Ronald F. Levant; Gerald Koocher; Sandra Shullman; and Rosie Phillips Bingham, APA Board of Directors liaison.

  2. Identification of novel interaction between ADAM17 (a disintegrin and metalloprotease 17) and thioredoxin-1.

    PubMed

    Aragão, Annelize Z B; Nogueira, Maria Luiza C; Granato, Daniela C; Simabuco, Fernando M; Honorato, Rodrigo V; Hoffman, Zaira; Yokoo, Sami; Laurindo, Francisco R M; Squina, Fabio M; Zeri, Ana Carolina M; Oliveira, Paulo S L; Sherman, Nicholas E; Paes Leme, Adriana F

    2012-12-14

    ADAM17, which is also known as TNFα-converting enzyme, is the major sheddase for the EGF receptor ligands and is considered to be one of the main proteases responsible for the ectodomain shedding of surface proteins. How a membrane-anchored proteinase with an extracellular catalytic domain can be activated by inside-out regulation is not completely understood. We characterized thioredoxin-1 (Trx-1) as a partner of the ADAM17 cytoplasmic domain that could be involved in the regulation of ADAM17 activity. We induced the overexpression of the ADAM17 cytoplasmic domain in HEK293 cells, and ligands able to bind this domain were identified by MS after protein immunoprecipitation. Trx-1 was also validated as a ligand of the ADAM17 cytoplasmic domain and full-length ADAM17 recombinant proteins by immunoblotting, immunolocalization, and solid phase binding assay. In addition, using nuclear magnetic resonance, it was shown in vitro that the titration of the ADAM17 cytoplasmic domain promotes changes in the conformation of Trx-1. The MS analysis of the cross-linked complexes showed cross-linking between the two proteins by lysine residues. To further evaluate the functional role of Trx-1, we used a heparin-binding EGF shedding cell model and observed that the overexpression of Trx-1 in HEK293 cells could decrease the activity of ADAM17, activated by either phorbol 12-myristate 13-acetate or EGF. This study identifies Trx-1 as a novel interaction partner of the ADAM17 cytoplasmic domain and suggests that Trx-1 is a potential candidate that could be involved in ADAM17 activity regulation.

  3. A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

    PubMed Central

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Suzuki, Maiko; Wada, Satoshi; Miyamoto, Yutaka; Yamaguchi, Yuuki; Katsumata, Yuta; Makihira, Seicho; Kawai, Toshi; Taubman, Martin A.; Nakamura, Yoshiki

    2016-01-01

    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. PMID:27573075

  4. A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma.

    PubMed

    Kanzaki, Hiroyuki; Shinohara, Fumiaki; Suzuki, Maiko; Wada, Satoshi; Miyamoto, Yutaka; Yamaguchi, Yuuki; Katsumata, Yuta; Makihira, Seicho; Kawai, Toshi; Taubman, Martin A; Nakamura, Yoshiki

    2016-01-01

    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases. PMID:27573075

  5. A new species of Spiroberotha Adams 1989 (Neuroptera: Berothidae) and the first record of the genus in Brazil.

    PubMed

    Machado, Renato Jose Pires; Krolow, Tiago Kütter

    2016-01-01

    The genus Spiroberotha Adams, 1989 is classified in Berothidae (Neuroptera) with two described species: S. fernandezi Adams, 1989 from Venezuela and S. sanctarosae Adams, 1989 from Colombia, Costa Rica and Venezuela. Here we describe a new species, S. tocantinensis n. sp., from Palmas, Tocantins, Brazil. This is the first record of the genus in Brazil, extending its geographical distribution. PMID:27394485

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

    SciTech Connect

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

  7. [Figures of first laureates of the Wiktor Dega medal (XXXVII Jubilee Congress of Polish Orthopaedic and Traumatologic Society, 10-13 September 2008)].

    PubMed

    Nowakowski, Andrzej; Rapała, Kazimierz

    2008-01-01

    Figures of two outstanding orthopaedists Professor Stefan Malawski and Professor Jerzy Król rewarded with the medal of the name of Wiktor Degi were described. The medal is being granted by the Chapter of the Medal as regarding for outstanding achievements for the Polish and world orthopaedics and rehabilitation. Profesor Stefan Kazimierz Malawski was born 26. 12. 1920 in the Vilnius area. In Vilnius he stated his medical studies, which he continued in Lwow and graduated in 1946 at the Marie Curie Skłodowska in Lublin. Professor Malawski's main field of interest were related to the problems related to tuberculosis of bones and joints and trauma of the lumbar and cervical spine. In the problems of bone tuberculosis he remains an unquestioned authority in Poland. His deep understanding of these clinical problems can be found in his text-book "Tuberculosis of bones and joints", which was printed in 1976. The information pertaining diagnosis and surgical treatment remain extremely valuable today. Another field of interest of Professor Malawski are pathologies of the spine. Disc disease, neoplasms of the spine, spinal stenosis and infections of the spine, spondylolisthesis are among many of his interests. This very wide field of interest can be dound in his 3 tome publication Spondyloorthopedics. His 166 papars printed in Poland and abroad bear proof of the Professors wide field of interest and deep knowledge. Professor Malawski was the first surgeon in Poland to perform surgery on the front elements of the spine in tuberculotic paraplegia. In 1958 he implemented surgical treatment of spine tumor--both primary and metastatic, by resecting them and stabilizing the spine with grafts. In the early 70's he focused on spinal stenosis. In the years 1982-1986 he was the Chairman of the Board of the Polish Orthopedic and Trauma Society. Professor Malawski introdued a modern set of Rules and Regulations, greatly simplifying the decision making process during General assemblies

  8. Econophysical visualization of Adam Smith’s invisible hand

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:25247288

  11. A Disintegrin and Metalloprotease (ADAM): Historical Overview of Their Functions

    PubMed Central

    Giebeler, Nives; Zigrino, Paola

    2016-01-01

    Since the discovery of the first disintegrin protein from snake venom and the following identification of a mammalian membrane-anchored metalloprotease-disintegrin implicated in fertilization, almost three decades of studies have identified additional members of these families and several biochemical mechanisms regulating their expression and activity in the cell. Most importantly, new in vivo functions have been recognized for these proteins including cell partitioning during development, modulation of inflammatory reactions, and development of cancers. In this review, we will overview the a disintegrin and metalloprotease (ADAM) family of proteases highlighting some of the major research achievements in the analysis of ADAMs’ function that have underscored the importance of these proteins in physiological and pathological processes over the years. PMID:27120619

  12. Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

    PubMed Central

    Davies, Elizabeth R.; Kelly, Joanne F.C.; Howarth, Peter H.; Wilson, David I.; Holgate, Stephen T.; Davies, Donna E.; Whitsett, Jeffrey A.

    2016-01-01

    Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma. PMID:27489884

  13. The ADAMs family of proteases as targets for the treatment of cancer.

    PubMed

    Mullooly, Maeve; McGowan, Patricia M; Crown, John; Duffy, Michael J

    2016-08-01

    The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anti-cancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown.

  14. SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation

    PubMed Central

    Saraceno, C; Marcello, E; Di Marino, D; Borroni, B; Claeysen, S; Perroy, J; Padovani, A; Tramontano, A; Gardoni, F; Di Luca, M

    2014-01-01

    A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP. PMID:25429624

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17

    PubMed Central

    Klingener, Michael; Raines, Elaine W.; Crawford, Howard C.

    2015-01-01

    The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair. SIGNIFICANCE STATEMENT Oligodendrocyte (OL) regeneration has emerged as a promising new approach for the treatment of demyelinating disorders. By using genetic mouse models to selectively delete TACE expression in oligodendrocyte progenitors cells (OPs), we found that TACE/ADAM17 is required for supporting OL regeneration following demyelination. TACE genetic depletion in OPs abrogates EGFR activation in OL lineage cells, and perturbs cell expansion and survival, blunting the process of CNS remyelination. Moreover, EGFR overexpression in TACE-deficient OPs in vivo overcomes the defects in OL development during postnatal development but also OL

  17. ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion.

    PubMed

    Aghababaei, M; Hogg, K; Perdu, S; Robinson, W P; Beristain, A G

    2015-12-01

    Trophoblasts, placental cells of epithelial lineage, undergo extensive differentiation to form the cellular components of the placenta. Trophoblast progenitor cell differentiation into the multinucleated syncytiotrophoblast is a key developmental process required for placental function, where defects in syncytiotrophoblast formation and turnover associate with placental pathologies and link to poor pregnancy outcomes. The cellular and molecular processes governing syncytiotrophoblast formation are poorly understood, but require the activation of pathways that direct cell fusion. The protease, A Disintegrin and Metalloproteinase 12 (ADAM12), controls cell fusion in myoblasts and is highly expressed in the placenta localizing to multiple trophoblast populations. However, the importance of ADAM12 in regulating trophoblast fusion is unknown. Here, we describe a function for ADAM12 in regulating trophoblast fusion. Using two distinct trophoblast models of cell fusion, we show that ADAM12 is dynamically upregulated and is under the transcriptional control of protein kinase A. siRNA-directed loss of ADAM12 impedes spontaneous fusion of primary cytotrophoblasts, whereas overexpression of the secreted variant, ADAM12S, potentiates cell fusion in the Bewo trophoblast cell line. Mechanistically, both ectopic and endogenous levels of ADAM12 were shown to control trophoblast fusion through E-cadherin ectodomain shedding and remodeling of intercellular boundaries. This study describes a novel role for ADAM12 in placental development, specifically highlighting its importance in controlling the differentiation of villous cytotrophoblasts into multinucleated cellular structures. Moreover, this work identifies E-cadherin as a novel ADAM12 substrate, and highlights the significance that cell adhesion molecule ectodomain shedding has in normal development.

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

    PubMed

    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.

  19. Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

    PubMed Central

    Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F

    2016-01-01

    Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. DOI: http://dx.doi.org/10.7554/eLife.12748.001 PMID:26802628

  20. The Role of SnoN in Transforming Growth Factor β1-induced Expression of Metalloprotease-Disintegrin ADAM12*

    PubMed Central

    Solomon, Emilia; Li, Hui; Duhachek Muggy, Sara; Syta, Emilia; Zolkiewska, Anna

    2010-01-01

    Increased expression of metalloprotease-disintegrin ADAM12 is a hallmark of several pathological conditions, including cancer, cardiovascular disease, and certain inflammatory diseases of the central nervous system or the muscoskeletal system. We show that transforming growth factor β1 (TGFβ1) is a potent inducer of ADAM12 mRNA and protein in mouse fibroblasts and in mouse and human mammary epithelial cells. Induction of ADAM12 is detected within 2 h of treatment with TGFβ1, is Smad2/Smad3-dependent, and is a result of derepression of the Adam12 gene. SnoN, a negative regulator of the TGFβ signaling pathway, is a master regulator of ADAM12 expression in response to TGFβ1 stimulation. Overexpression of SnoN in NIH3T3 cells reduces the magnitude of ADAM12 induction by TGFβ1 treatment. Down-regulation of SnoN expression by short hairpin RNA enhances TGFβ1-induced expression of ADAM12. In a panel of TGFβ1-responsive cancer cell lines with high expression of SnoN, induction of ADAM12 by TGFβ1 is significantly impaired, suggesting that the endogenous SnoN plays a role in regulating ADAM12 expression in response to TGFβ1. Identification of SnoN as a repressor of the ADAM12 gene should contribute to advances in the studies on the role of ADAM12 in tumor progression and in the development of other pathologies. PMID:20457602

  1. iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding

    PubMed Central

    Maretzky, Thorsten; McIlwain, David R.; Issuree, Priya Darshinee A.; Li, Xue; Malapeira, Jordi; Amin, Sadaf; Lang, Philipp A.; Mak, Tak W.; Blobel, Carl P.

    2013-01-01

    Protein ectodomain shedding by ADAM17 (a disintegrin and metalloprotease 17), a principal regulator of EGF-receptor signaling and TNFα release, is rapidly and posttranslationally activated by a variety of signaling pathways, and yet little is known about the underlying mechanism. Here, we report that inactive rhomboid protein 2 (iRhom2), recently identified as essential for the maturation of ADAM17 in hematopoietic cells, is crucial for the rapid activation of the shedding of some, but not all substrates of ADAM17. Mature ADAM17 is present in mouse embryonic fibroblasts (mEFs) lacking iRhom2, and yet ADAM17 is unable to support stimulated shedding of several of its substrates, including heparin-binding EGF and Kit ligand 2 in this context. Stimulated shedding of other ADAM17 substrates, such as TGFα, is not affected in iRhom2−/− mEFs but can be strongly reduced by treating iRhom2−/− mEFs with siRNA against iRhom1. Activation of heparin-binding EGF or Kit ligand 2 shedding by ADAM17 in iRhom2−/− mEFs can be rescued by wild-type iRhom2 but not by iRhom2 lacking its N-terminal cytoplasmic domain. The requirement for the cytoplasmic domain of iRhom2 for stimulated shedding by ADAM17 may help explain why the cytoplasmic domain of ADAM17 is not required for stimulated shedding. The functional relevance of iRhom2 in regulating shedding of EGF receptor (EGFR) ligands is established by a lack of lysophasphatidic acid/ADAM17/EGFR-dependent crosstalk with ERK1/2 in iRhom2−/− mEFs, and a significant reduction of FGF7/ADAM17/EGFR-stimulated migration of iRhom2−/− keratinocytes. Taken together, these findings uncover functions for iRhom2 in the regulation of EGFR signaling and in controlling the activation and substrate selectivity of ADAM17-dependent shedding events. PMID:23801765

  2. The thrill of victory and the agony of defeat: spontaneous expressions of medal winners of the 2004 Athens Olympic Games.

    PubMed

    Matsumoto, David; Willingham, Bob

    2006-09-01

    Facial behaviors of medal winners of the judo competition at the 2004 Athens Olympic Games were coded with P. Ekman and W. V. Friesen's (1978) Facial Affect Coding System (FACS) and interpreted using their Emotion FACS dictionary. Winners' spontaneous expressions were captured immediately when they completed medal matches, when they received their medal from a dignitary, and when they posed on the podium. The 84 athletes who contributed expressions came from 35 countries. The findings strongly supported the notion that expressions occur in relation to emotionally evocative contexts in people of all cultures, that these expressions correspond to the facial expressions of emotion considered to be universal, that expressions provide information that can reliably differentiate the antecedent situations that produced them, and that expressions that occur without inhibition are different than those that occur in social and interactive settings.

  3. Highlighting High Performance: Adam Joseph Lewis Center for Environmental Studies, Oberlin College, Oberlin, Ohio

    SciTech Connect

    2002-11-01

    Oberlin College’s Adam Joseph Lewis Center for Environmental Studies is a high-performance building featuring an expansive photovoltaic system and a closed-loop groundwater heat pump system. Designers incorporated energy-efficient components and materials

  4. The SEAD global efficiency medal competition: accelerating market transformation for efficient televisions

    SciTech Connect

    Ravi, Kavita; Bennich, Peter; Cockburn, John; Doi, Naoko; Garg, Sandeep; Garnaik, S.P.; Holt, Shane; Walker, Mike; Westbrook-Trenholm, Elizabeth; Lising, Anna; Pantano, Steve; Khare, Amit; Park, Won Young

    2013-10-15

    The Global Efficiency Medal competition, a cornerstone activity of the Super-efficient Equipment and Appliance Deployment (SEAD) Initiative, is an awards program that encourages the production and sale of super-efficient products. SEAD is a voluntary multinational government collaboration of the Clean Energy Ministerial (CEM). This winner-takes-all competition recognizes products with the best energy efficiency, guides early adopter purchasers towards the most efficient product choices and demonstrates the levels of energy efficiency achievable by commercially available and emerging technologies. The first Global Efficiency Medals were awarded to the most energy-efficient flat panel televisions; an iconic consumer purchase. SEAD Global Efficiency Medals were awarded to televisions that have proven to be substantially more energy efficient than comparable models available at the time of the competition (applications closed in the end of May 2012). The award-winning TVs consume between 33 to 44 percent less energy per 2 unit of screen area than comparable LED-backlit LCD televisions sold in each regional market and 50 to 60 percent less energy than CCFL-backlit LCD TVs. Prior to the launch of this competition, SEAD conducted an unprecedented international round-robin test (RRT) to qualify TV test laboratories to support verification testing for SEAD awards. The RRT resulted in increased test laboratory capacity and expertise around the world and ensured that the test results from participating regional test laboratories could be compared in a fair and transparent fashion. This paper highlights a range of benefits resulting from this first SEAD awards competition and encourages further investigation of the awards concept as a means to promote energy efficiency in other equipment types.

  5. CCD Photometry and Lightcurve Analysis of 1730 Marceline and 1996 Adams from Observatori Carmelita in Tiana

    NASA Astrophysics Data System (ADS)

    Aymami, Josep Maria

    2011-01-01

    Analysis of observations carried out during 2010 September and October determined the synodic periods of 1730 Marceline (1936 UA) and 1996 Adams (1961 UA). For main-belt asteroid 1730 Marceline, a period of 3.837 ± 0.001 h was found. For 1996 Adams, also an MBA, a period of 3.311 ± 0.001 h was determined. This differs from the period of 3.56 h found by Alvarez-Candal et al. (2004).

  6. MicroRNA-147b Regulates Vascular Endothelial Barrier Function by Targeting ADAM15 Expression

    PubMed Central

    Chatterjee, Victor; Beard, Richard S.; Reynolds, Jason J.; Haines, Ricci; Guo, Mingzhang; Rubin, Matthew; Guido, Jenny; Wu, Mack H.; Yuan, Sarah Y.

    2014-01-01

    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. PMID:25333931

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

    PubMed

    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. PMID:16586236

  8. ADAM17 Inhibitors Attenuate Corneal Epithelial Detachment Induced by Mustard Exposure

    PubMed Central

    DeSantis-Rodrigues, Andrea; Chang, Yoke-Chen; A. Hahn, Rita; P. Po, Iris; Zhou, Peihong; Lacey, C. Jeffrey; Pillai, Abhilash; C. Young, Sherri; A. Flowers II, Robert; A. Gallo, Michael; D. Laskin, Jeffrey; R. Gerecke, Donald; K. H. Svoboda, Kathy; D. Heindel, Ned; Gordon, Marion K.

    2016-01-01

    Purpose Sulfur mustard, nitrogen mustard (NM), and 2-chloroethyl ethyl sulfide all cause corneal injury with epithelial–stromal separation, differing only by degree. Injury can resolve in a few weeks or develop into chronic corneal problems. These vesicants induce microbullae at the epithelial–stromal junction, which is partially caused by cleavage of transmembranous hemidesmosomal collagen XVII, a component anchoring the epithelium to the stroma. ADAM17 is an enzyme involved in wound healing and is able to cleave collagen XVII. The activity of ADAM17 was inhibited in vesicant-exposed corneas by four different hydroxamates, to evaluate their therapeutic potential when applied 2 hours after exposure, thereby allowing ADAM17 to perform its early steps in wound healing. Methods Rabbit corneal organ cultures exposed to NM for 2 hours were washed, then incubated at 37°C for 22 hours, with or without one of the four hydroxamates (dose range, 0.3–100 nmol in 20 μL, applied four times). Corneas were analyzed by light and immunofluorescence microscopy, and ADAM17 activity assays. Results Nitrogen mustard–induced corneal injury showed significant activation of ADAM17 levels accompanying epithelial–stromal detachment. Corneas treated with hydroxamates starting 2 hours post exposure showed a dose-dependent ADAM17 activity inhibition up to concentrations of 3 nmol. Of the four hydroxamates, NDH4417 (N-octyl-N-hydroxy-2-[4-hydroxy-3-methoxyphenyl] acetamide) was most effective for inhibiting ADAM17 and retaining epithelial–stromal attachment. Conclusions Mustard exposure leads to corneal epithelial sloughing caused, in part, by the activation of ADAM17 at the epithelial–stromal junction. Select hydroxamate compounds applied 2 hours after NM exposure mitigated epithelial–stromal separation. PMID:27058125

  9. A novel peptide ADAM8 inhibitor attenuates bronchial hyperresponsiveness and Th2 cytokine mediated inflammation of murine asthmatic models

    PubMed Central

    Chen, Jun; Deng, Linhong; Dreymüller, Daniela; Jiang, Xuemei; Long, Jiaoyue; Duan, Yiyuan; Wang, Yue; Luo, Mingzhi; Lin, Feng; Mao, Lizhen; Müller, Bernd; Koller, Garrit; Bartsch, Jörg W.

    2016-01-01

    A disintegrin and metalloproteinase 8 (ADAM8) has been identified as a signature gene associated with moderate and severe asthma. Studies in mice have demonstrated that the severity of asthma can be reduced by either transgenic knock-out or by antibodies blocking ADAM8 function, highlighting ADAM8 as potential drug target for asthma therapy. Here, we examined the therapeutic effect of an ADAM8 inhibitor peptide (BK-1361) that specifically blocks cellular ADAM8 activity in ovalbumin-sensitized and challenged Balb/c mice. We found that BK-1361 (25 μg/g body weight) attenuated airway responsiveness to methacholine stimulation by up to 42%, concomitantly reduced tissue remodeling by 50%, and decreased inflammatory cells (e.g. eosinophils down by 54%)/inflammatory factors (e.g. sCD23 down by 50%)/TH2 cytokines (e.g. IL-5 down by 70%)/ADAM8-positive eosinophils (down by 60%) in the lung. We further verified that BK-1361 specifically targets ADAM8 in vivo as the peptide caused significantly reduced levels of soluble CD23 in wild-type but not in ADAM8-deficient mice. These findings suggest that BK-1361 blocks ADAM8-dependent asthma effects in vivo by inhibiting infiltration of eosinophils and TH2 lymphocytes, thus leading to reduction of TH2-mediated inflammation, tissue remodeling and bronchial hyperresponsiveness. Taken together, pharmacological ADAM8 inhibition appears as promising novel therapeutic strategy for the treatment of asthma. PMID:27458083

  10. Rhythm Analyses Of Melodies Used To Obtain Women Marathon Gold Medal

    NASA Astrophysics Data System (ADS)

    Tacano, Munecazu; Yokokura, Saburo; Kajiwara, Yoko; Pavelka, Jan; Tanuma, Nobuhisa; Uemura, Tatsuhisa; Hashiguchi, Sumihisa; Sikula, Josef

    2005-11-01

    In Athena Olympics in 2004 a Japanese girl got the gold medal in Women Marathon games. Just before the beginning, she was listening to some domestic melodies in order to concentrate on the race. The rhythm or power of that music is found to have the typical 1/f noise characteristics. The 1/f music is found effective to concentrate as well as to relax themselves for a fairly long time range, while some short time trial runner uses a kind of white noise like music.

  11. Geologic map and geothermal assessment of the Mount Adams volcanic field, Cascade Range of southern Washington

    USGS Publications Warehouse

    Hildreth, Wes; Fierstein, Judy

    1990-01-01

    More than 60 Quaternary vents make up the basalt-to-rhyodacite Mount Adams volcanic field and have erupted scoriae and lavas with a total volume of >370 km3. The Mount Adams andesite-dacite stratocone itself is a compound edifice that includes the high cone above 2300 m (20-10 ka), remnants of at least two earlier andesite-dacite cones as old as 0.5 Ma, and 7 Holocene flank vents. Four other Holocene vents and tens of vents contemporaneous with Mount Adams are peripheral to the stratocone. All of these vents, including Mount Adams, lie within a N-S eruptive zone 55 km long and 5 km wide. The age of all known Mount Adams silicic products (>100 ka) and the heterogeneous mafic compositions of the summit cone and Holocene lavas make it unlikely that the stratocone is underlain by an upper-crustal reservoir. Rather, the stratocone at the focus is built up of fractionated hybrid magmas that rise from MASH zones (melting-assimilation-storage-homogenization). The pyroclastic core of breccia and scoria at Mount Adams has undergone acid-sulfate leaching and deposition of alunite, kaolinite, silica, gypsum, sulfur, and Fe-oxides and has been a constant source of avalanches and debris flows. Most heat supplied from depth to the fumarolically altered core is dispersed by the high precipitation rate and high permeability of the rubbly lava flows so that a hydrothermal convection pattern is not maintained. Summit-restricted fumaroles are weak and diffuse.

  12. The Low Affinity IgE Receptor (CD23) Is Cleaved by the Metalloproteinase ADAM10*

    PubMed Central

    Lemieux, George A.; Blumenkron, Fernando; Yeung, Nolan; Zhou, Pei; Williams, Jason; Grammer, Amrie C.; Petrovich, Robert; Lipsky, Peter E.; Moss, Marcia L.; Werb, Zena

    2008-01-01

    The low affinity IgE receptor, Fc∊RII (CD23), is both a positive and negative regulator of IgE synthesis. The proteinase activity that converts the membrane-bound form of CD23 into a soluble species (sCD23) is an important regulator of the function of CD23 and may be an important therapeutic target for the control of allergy and inflammation. We have characterized the catalytic activity of ADAM (a disintegrin and metalloproteinase) 10 toward human CD23. We found that ADAM10 efficiently catalyzes the cleavage of peptides derived from two distinct cleavage sites in the CD23 backbone. Tissue inhibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release of endogenously produced CD23 from human leukemia cell lines as well as primary cultures of human B-cells. Expression of a mutant metalloproteinase-deficient construct of ADAM10 partially inhibited the production of sCD23. Similarly, small inhibitory RNA knockdown of ADAM10 partially inhibited CD23 release and resulted in the accumulation of the membrane-bound form of CD23 on the cells. ADAM10 contributes to CD23 shedding and thus could be considered a potential therapeutic target for the treatment of allergic disease. PMID:17389606

  13. The low affinity IgE receptor (CD23) is cleaved by the metalloproteinase ADAM10.

    PubMed

    Lemieux, George A; Blumenkron, Fernando; Yeung, Nolan; Zhou, Pei; Williams, Jason; Grammer, Amrie C; Petrovich, Robert; Lipsky, Peter E; Moss, Marcia L; Werb, Zena

    2007-05-18

    The low affinity IgE receptor, FcepsilonRII (CD23), is both a positive and negative regulator of IgE synthesis. The proteinase activity that converts the membrane-bound form of CD23 into a soluble species (sCD23) is an important regulator of the function of CD23 and may be an important therapeutic target for the control of allergy and inflammation. We have characterized the catalytic activity of ADAM (a disintegrin and metalloproteinase) 10 toward human CD23. We found that ADAM10 efficiently catalyzes the cleavage of peptides derived from two distinct cleavage sites in the CD23 backbone. Tissue inhibitors of metalloproteinases and a specific prodomain-based inhibitor of ADAM10 perturb the release of endogenously produced CD23 from human leukemia cell lines as well as primary cultures of human B-cells. Expression of a mutant metalloproteinase-deficient construct of ADAM10 partially inhibited the production of sCD23. Similarly, small inhibitory RNA knockdown of ADAM10 partially inhibited CD23 release and resulted in the accumulation of the membrane-bound form of CD23 on the cells. ADAM10 contributes to CD23 shedding and thus could be considered a potential therapeutic target for the treatment of allergic disease.

  14. Lrig2 Negatively Regulates Ectodomain Shedding of Axon Guidance Receptors by ADAM Proteases.

    PubMed

    van Erp, Susan; van den Heuvel, Dianne M A; Fujita, Yuki; Robinson, Ross A; Hellemons, Anita J C G M; Adolfs, Youri; Van Battum, Eljo Y; Blokhuis, Anna M; Kuijpers, Marijn; Demmers, Jeroen A A; Hedman, Håkan; Hoogenraad, Casper C; Siebold, Christian; Yamashita, Toshihide; Pasterkamp, R Jeroen

    2015-12-01

    Many guidance receptors are proteolytically cleaved by membrane-associated metalloproteases of the ADAM family, leading to the shedding of their ectodomains. Ectodomain shedding is crucial for receptor signaling and function, but how this process is controlled in neurons remains poorly understood. Here, we show that the transmembrane protein Lrig2 negatively regulates ADAM-mediated guidance receptor proteolysis in neurons. Lrig2 binds Neogenin, a receptor for repulsive guidance molecules (RGMs), and prevents premature Neogenin shedding by ADAM17 (TACE). RGMa reduces Lrig2-Neogenin interactions, providing ADAM17 access to Neogenin and allowing this protease to induce ectodomain shedding. Regulation of ADAM17-mediated Neogenin cleavage by Lrig2 is required for neurite growth inhibition by RGMa in vitro and for cortical neuron migration in vivo. Furthermore, knockdown of Lrig2 significantly improves CNS axon regeneration. Together, our data identify a unique ligand-gated mechanism to control receptor shedding by ADAMs and reveal functions for Lrigs in neuron migration and regenerative failure. PMID:26651291

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

    SciTech Connect

    Elliott, A.S.; Depauw, T.R.

    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.

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

    PubMed Central

    Takeda, Soichi

    2016-01-01

    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. PMID:27196928

  17. A-Disintegrin-And-Metalloproteinase (ADAM) 10 Activity on Resting and Activated Platelets.

    PubMed

    Facey, Adam; Pinar, Isaac; Arthur, Jane F; Qiao, Jianlin; Jing, Jing; Mado, Belden; Carberry, Josie; Andrews, Robert K; Gardiner, Elizabeth E

    2016-03-01

    The primary platelet collagen receptor, glycoprotein VI (GPVI), plays an important role in platelet activation and thrombosis. The ectodomain of human GPVI (sGPVI) is proteolytically shed from human platelets by a-disintegrin-and-metalloproteinase 10 (ADAM10). In this study, we used a novel ADAM10-sensitive fluorescence resonance energy transfer sensor to analyze ADAM10-mediated shedding of GPVI from human platelets in response to the exposure of GPVI ligands collagen-related peptide (10 μg/mL), collagen (10 μg/mL), and convulxin (0.1 μg/mL) to shear stress (1000-10000 s(-1), 5 min), or a generic activator of metalloproteinases, N-ethylmaleimide (NEM, 5 mM). Elevated shear, NEM, or ligand engagement of GPVI all induced shedding of GPVI, as detected by release of sGPVI; however, only shear or NEM significantly increased ADAM10 enzyme activity. ADAM10 activity was also detectable on the surface of thrombi formed on a collagen-coated surface under flow conditions. Our findings indicate different mechanisms regulate shear- and ligand-induced shedding and shear forces found within the vasculature can regulate ADAM10 activity. PMID:26840909

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

    PubMed

    Sanchez-Guerrero, Estella; Chen, Elya; Kockx, Maaike; An, Si-Wei; Chong, Beng H; Khachigian, Levon M

    2012-01-01

    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. PMID:22792188

  19. What Color Is Gold? Twenty-One Years of Same-Race Authors and Protagonists in the Newbery Medal.

    ERIC Educational Resources Information Center

    Miller, Bonnie J. F.

    1998-01-01

    Discusses the lack of minority representation of both authors and protagonists in the Newbery Medal books which are recognized as the most distinguished contributions to American children's literature. Topics include the subjectivity involved in deciding what book is distinguished enough for an award and older books that have racial stereotypes.…

  20. 45 CFR 2102.11 - Scope and content of submissions for proposed medals, insignia, coins, seals, and the like.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Scope and content of submissions for proposed medals, insignia, coins, seals, and the like. 2102.11 Section 2102.11 Public Welfare Regulations Relating..., insignia, coins, seals, and the like. Each submission of the design for a proposed item which is within...

  1. [Webometrics – on the occasion of the awarding of the Derek John de Solla Price Medal, 2015].

    PubMed

    Schubert, András

    2015-09-01

    The most significant recognition in scientometrics, the Derek John de Solla Price Medal was awarded in 2015 to Mike Thelwall. Thelwall is a dominant personality in webometrics studying the internet presence of scientific research with quantitative methods. In this paper the emergence, standing and directions of webometrics are briefly reviewed.

  2. Learning Strategies in Play during Basic Training for Medal of Honor and Call of Duty Video Games

    ERIC Educational Resources Information Center

    Ziaeehezarjeribi, Yadi

    2010-01-01

    This study, based on experiential play methodology was used to explore student engagement while playing "Medal of Honor (2002)" and "Call of Duty (2003)". It identifies some of the key issues related to the use of video games and simulations during the training phase of game play. Research into the effects of gaming in education has been extremely…

  3. 45 CFR 2102.11 - Scope and content of submissions for proposed medals, insignia, coins, seals, and the like.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Scope and content of submissions for proposed medals, insignia, coins, seals, and the like. 2102.11 Section 2102.11 Public Welfare Regulations Relating..., insignia, coins, seals, and the like. Each submission of the design for a proposed item which is within...

  4. 45 CFR 2102.11 - Scope and content of submissions for proposed medals, insignia, coins, seals, and the like.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Scope and content of submissions for proposed medals, insignia, coins, seals, and the like. 2102.11 Section 2102.11 Public Welfare Regulations Relating..., insignia, coins, seals, and the like. Each submission of the design for a proposed item which is within...

  5. MT5-MMP, ADAM-10, and N-Cadherin Act in Concert To Facilitate Synapse Reorganization after Traumatic Brain Injury

    PubMed Central

    Warren, Kelly M.; Reeves, Thomas M.

    2012-01-01

    Abstract Matrix metalloproteinases (MMPs) influence synaptic recovery following traumatic brain injury (TBI). Membrane type 5-matrix metalloproteinase (MT5-MMP) and a distintegrin and metalloproteinase-10 (ADAM-10) are membrane-bound MMPs that cleave N-cadherin, a protein critical to synapse stabilization. This study examined protein and mRNA expression of MT5-MMP, ADAM-10, and N-cadherin after TBI, contrasting adaptive and maladaptive synaptogenesis. The effect of MMP inhibition on MT5-MMP, ADAM-10, and N-cadherin was assessed during maladaptive plasticity and correlated with synaptic function. Rats were subjected to adaptive unilateral entorhinal cortical lesion (UEC) or maladaptive fluid percussion TBI+bilateral entorhinal cortical lesion (TBI+BEC). Hippocampal MT5-MMP and ADAM-10 protein was significantly elevated 2 and 7 days post-injury. At 15 days after UEC, each MMP returned to control level, while TBI+BEC ADAM-10 remained elevated. At 2 and 7 days, N-cadherin protein was below control. By the 15-day synapse stabilization phase, UEC N-cadherin rose above control, a shift not seen for TBI+BEC. At 7 days, increased TBI+BEC ADAM-10 transcript correlated with protein elevation. UEC ADAM-10 mRNA did not change, and no differences in MT5-MMP or N-cadherin mRNA were detected. Confocal imaging showed MT5-MMP, ADAM-10, and N-cadherin localization within reactive astrocytes. MMP inhibition attenuated ADAM-10 protein 15 days after TBI+BEC and increased N-cadherin. This inhibition partially restored long-term potentiation induction, but did not affect paired-pulse facilitation. Our results confirm time- and injury-dependent expression of MT5-MMP, ADAM-10, and N-cadherin during reactive synaptogenesis. Persistent ADAM-10 expression was correlated with attenuated N-cadherin level and reduced functional recovery. MMP inhibition shifted ADAM-10 and N-cadherin toward adaptive expression and improved synaptic function. PMID:22489706

  6. ADAM22, a Kv1 channel-interacting protein, recruits membrane-associated guanylate kinases to juxtaparanodes of myelinated axons.

    PubMed

    Ogawa, Yasuhiro; Oses-Prieto, Juan; Kim, Moon Young; Horresh, Ido; Peles, Elior; Burlingame, Alma L; Trimmer, James S; Meijer, Dies; Rasband, Matthew N

    2010-01-20

    Clustered Kv1 K(+) channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments, and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 alpha subunits, and then used mass spectrometry to identify interacting proteins. We found that a disintegrin and metalloproteinase 22 (ADAM22) is a component of the Kv1 channel complex and that ADAM22 coimmunoprecipitates Kv1.2 and the membrane-associated guanylate kinases (MAGUKs) PSD-93 and PSD-95. When coexpressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, coexpression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel-interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis of Caspr-null mice showed that, like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis of Caspr2-, PSD-93-, PSD-95-, and double PSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis of ADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal in ADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K(+) channel complex that recruits MAGUKs to juxtaparanodes. PMID:20089912

  7. Monocyte ADAM17 promotes diapedesis during transendothelial migration: Identification of steps and substrates targeted by metalloproteinases

    PubMed Central

    Tsubota, Yoshiaki; Frey, Jeremy M.; Tai, Phillip W.L.; Welikson, Robert E.; Raines, Elaine W.

    2013-01-01

    Despite expanded definition of the leukocyte adhesion cascade and mechanisms underlying individual steps, very little is known about regulatory mechanisms controlling sequential shifts between steps. We tested the hypothesis that metalloproteinases provide a mechanism to rapidly transition monocytes between different steps. Our study identifies diapedesis as a step targeted by metalloproteinase activity. Time-lapse video microscopy shows that the presence of a metalloproteinase inhibitor results in a doubling of the time required for human monocytes to complete diapedesis on unactivated or inflamed human endothelium, under both static and physiological-flow conditions. Thus, diapedesis is promoted by metalloproteinase activity. In contrast, neither adhesion of monocytes nor their locomotion over the endothelium is altered by metalloproteinase inhibition. We further demonstrate that metalloproteinase inhibition significantly elevates monocyte cell-surface levels of integrins CD11b/CD18 (Mac-1) specifically during transendothelial migration. Interestingly, such alterations are not detected for other endothelial- and monocyte-adhesion molecules that are presumed metalloproteinase substrates. Two major transmembrane metalloproteinases, ADAM17 and ADAM10, are identified as enzymes that control constitutive cleavage of Mac-1. We further establish that knockdown of monocyte ADAM17, but not endothelial ADAM10 or ADAM17, or monocyte ADAM10, reproduces the diapedesis delay observed with metalloproteinase inhibition. Therefore, we conclude that monocyte ADAM17 facilitates the completion of transendothelial migration by accelerating the rate of diapedesis. We propose that the progression of diapedesis may be regulated by spatial and temporal cleavage of Mac-1, which is triggered upon interaction with endothelium. PMID:23479224

  8. Fendiline inhibits proliferation and invasion of pancreatic cancer cells by interfering with ADAM10 activation and β-catenin signaling

    PubMed Central

    Woods, Neha; Trevino, Jose; Coppola, Domenico; Chellappan, Srikumar; Yang, Shengyu; Padmanabhan, Jaya

    2015-01-01

    ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology of various cancers, and we had shown that inhibition of ADAM10 sensitizes pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to calcium influx, and here we examined if calcium channel blockers (CCB) would impede ADAM10 activation and affect biology of pancreatic cancer cells. We find that the CCB, fendiline, significantly reduces proliferation, migration, invasion, and anchorage independent growth of pancreatic cancer cells. This was associated with ADAM10 inhibition and its localization at the actin-rich membrane protrusions. Further, fendiline-treated cells formed cadherin-catenin positive tight adherens junctions and elicited defective protein trafficking and recycling. Furthermore, the expression of β-catenin target genes, cyclinD1, c-Myc and CD44, were significantly decreased, suggesting that fendiline might prevent cell proliferation and migration by inhibiting ADAM10 function, cadherin proteolysis and stabilization of cadherin-catenin interaction at the plasma membrane. This will subsequently diminish β-catenin intracellular signaling and repress TCF/LEF target gene expression. Supporting this notion, RNAi-directed downregulation of ADAM10 in cancer cells decreased the expression of cyclinD1, c-Myc and CD44. Furthermore, analysis of human pancreatic tumor tissue microarrays and lysates showed elevated levels of ADAM10, suggesting that aberrant activation of ADAM10 plays a fundamental role in growth and metastasis of PDACs and inhibiting this pathway might be a viable strategy to combat PDACs. PMID:26440150

  9. Effect of a dominant-negative form of ADAM10 in a mouse model of Alzheimer's disease.

    PubMed

    Schroeder, Anja; Fahrenholz, Falk; Schmitt, Ulrich

    2009-01-01

    The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid-beta protein precursor (AbetaPP) within the region of the amyloid-beta peptides to prevent their formation and aggregation in the brain. Members of the ADAM family (a disintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. We recently demonstrated that overexpression of ADAM10 in mice transgenic for human AbetaPP (ADAM10 x APP[V717I]) alleviated functional deficits related to Alzheimer's disease. To further demonstrate that this is due to the specific activity of alpha-secretase, we characterized mice overexpressing an inactive form of ADAM10 (ADAM10[E384A]; ADAM10-dn). Three lines of mice (controls (C57Bl/6 x FVB), APP[V717I[ transgenics and ADAM10-dn x APP[V717I] double-transgenics) were investigated with respect to learning and memory in the Morris water maze. Double-transgenic mice overexpressing ADAM10-dn behaved similar to APP[V717I] overexpressing mice. This provides further evidence that ADAM10 in vivo by its enzymatic activity is able to counteract cognitive deficits. Stimulation of alpha-secretase activity might thus be a suitable approach to study treatment strategies of Alzheimer's disease.

  10. Analysis of mixed model in gear transmission based on ADAMS

    NASA Astrophysics Data System (ADS)

    Li, Xiufeng; Wang, Yabin

    2012-09-01

    The traditional method of mechanical gear driving simulation includes gear pair method and solid to solid contact method. The former has higher solving efficiency but lower results accuracy; the latter usually obtains higher precision of results while the calculation process is complex, also it is not easy to converge. Currently, most of the researches are focused on the description of geometric models and the definition of boundary conditions. However, none of them can solve the problems fundamentally. To improve the simulation efficiency while ensure the results with high accuracy, a mixed model method which uses gear tooth profiles to take the place of the solid gear to simulate gear movement is presented under these circumstances. In the process of modeling, build the solid models of the mechanism in the SolidWorks firstly; Then collect the point coordinates of outline curves of the gear using SolidWorks API and create fit curves in Adams based on the point coordinates; Next, adjust the position of those fitting curves according to the position of the contact area; Finally, define the loading conditions, boundary conditions and simulation parameters. The method provides gear shape information by tooth profile curves; simulates the mesh process through tooth profile curve to curve contact and offer mass as well as inertia data via solid gear models. This simulation process combines the two models to complete the gear driving analysis. In order to verify the validity of the method presented, both theoretical derivation and numerical simulation on a runaway escapement are conducted. The results show that the computational efficiency of the mixed model method is 1.4 times over the traditional method which contains solid to solid contact. Meanwhile, the simulation results are more closely to theoretical calculations. Consequently, mixed model method has a high application value regarding to the study of the dynamics of gear mechanism.

  11. Mutations in NOTCH1 cause Adams-Oliver syndrome.

    PubMed

    Stittrich, Anna-Barbara; Lehman, Anna; Bodian, Dale L; Ashworth, Justin; Zong, Zheyuan; Li, Hong; Lam, Patricia; Khromykh, Alina; Iyer, Ramaswamy K; Vockley, Joseph G; Baveja, Rajiv; Silva, Ermelinda Santos; Dixon, Joanne; Leon, Eyby L; Solomon, Benjamin D; Glusman, Gustavo; Niederhuber, John E; Roach, Jared C; Patel, Millan S

    2014-09-01

    Notch signaling determines and reinforces cell fate in bilaterally symmetric multicellular eukaryotes. Despite the involvement of Notch in many key developmental systems, human mutations in Notch signaling components have mainly been described in disorders with vascular and bone effects. Here, we report five heterozygous NOTCH1 variants in unrelated individuals with Adams-Oliver syndrome (AOS), a rare disease with major features of aplasia cutis of the scalp and terminal transverse limb defects. Using whole-genome sequencing in a cohort of 11 families lacking mutations in the four genes with known roles in AOS pathology (ARHGAP31, RBPJ, DOCK6, and EOGT), we found a heterozygous de novo 85 kb deletion spanning the NOTCH1 5' region and three coding variants (c.1285T>C [p.Cys429Arg], c.4487G>A [p.Cys1496Tyr], and c.5965G>A [p.Asp1989Asn]), two of which are de novo, in four unrelated probands. In a fifth family, we identified a heterozygous canonical splice-site variant (c.743-1 G>T) in an affected father and daughter. These variants were not present in 5,077 in-house control genomes or in public databases. In keeping with the prominent developmental role described for Notch1 in mouse vasculature, we observed cardiac and multiple vascular defects in four of the five families. We propose that the limb and scalp defects might also be due to a vasculopathy in NOTCH1-related AOS. Our results suggest that mutations in NOTCH1 are the most common cause of AOS and add to a growing list of human diseases that have a vascular and/or bony component and are caused by alterations in the Notch signaling pathway. PMID:25132448

  12. Role of integrins, tetraspanins, and ADAM proteins during the development of apoptotic bodies by spermatogenic cells.

    PubMed

    Kierszenbaum, Abraham L; Rosselot, Carolina; Rivkin, Eugene; Tres, Laura L

    2006-07-01

    We have previously reported that Sertoli cell geometric changes induced by a Fas (CD95) agonist or by restricting Sertoli cell spreading can trigger spermatogenic cell detachment from Sertoli cell surfaces and initiate a programmed cell death sequence. Here, we have focused on ADAM proteins, tetraspanins CD9 and CD81, and the integrin beta1 subunit, which is co-expressed in testis with integrin alpha3 and integrin alpha6 subunits, to understand how these molecules may stabilize spermatogenic cell attachment to Sertoli cell surfaces. Like ADAM proteins, integrin beta1, alpha3, and alpha6 subunits, and CD9 and CD81 transcripts are expressed in the fetal testis and throughout testicular maturation, as well as, in Sertoli-spermatogenic cell co-cultures. Prespermatogonia (gonocytes) display CD9 and CD81 immunoreactive sites. Integrin alpha6 subunit transcripts have unusual developmental characteristics: fetal testis expresses the integrin alpha6B isoform exclusively. In contrast, the integrin alpha6B isoform co-exists with the integrin alpha6A isoform in prepubertal testes and Sertoli-spermatogenic cell co-cultures. A blocking anti body targeting the extracellular domain (N-terminal) of the integrin beta1 subunit causes rapid contraction of Sertoli cells leading to the gradual detachment of associated spermatogenic cells. In contrast, predicted active site peptides targeting the disintegrin domain of ADAM 1, ADAM 2, ADAM 3 (cyritestin), ADAM 4, ADAM 5, ADAM 6, and ADAM 15 (metragidin) do not disturb significantly the attachment of spermatogenic cells to Sertoli cell surfaces. Spermatogenic cells dislodged from their attachment sites by the integrin beta1 subunit blocking antibody display annexin V immunoreactivity, a sign of early apoptosis. Time-lapse videomicroscopy demonstrates that the removal by apoptosis of a single member of a spermatogenic cell cohort inter-connected by cytoplasmic bridges does not affect the remaining members of the cohort. During spermatogenic

  13. Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways.

    PubMed

    Dang, Michelle; Armbruster, Nicole; Miller, Miles A; Cermeno, Efrain; Hartmann, Monika; Bell, George W; Root, David E; Lauffenburger, Douglas A; Lodish, Harvey F; Herrlich, Andreas

    2013-06-11

    Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1 inhibitor 14D that is required for ADAM17 cleavage of TGF-α, heparin-binding EGF, and amphiregulin. A second pathway involving PKC-δ is required for neuregulin (NRG) cleavage, and, indeed, PKC-δ phosphorylation of serine 286 in the NRG cytosolic domain is essential for induced NRG cleavage. Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease.

  14. ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors.

    PubMed

    Becker, Amy M; Walcheck, Bruce; Bhattacharya, Deepta

    2015-01-01

    All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through posttranscriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of CSF1R transcripts than their upstream precursors, yet show limited cell-surface protein expression of colony-stimulating factor 1 receptor (CSF1R). All-lymphoid progenitors and other hematopoietic progenitors deficient in A disintegrin and metalloproteinase domain 17 (ADAM17), display elevated cell surface CSF1R expression. ADAM17(-/-) ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, ADAM17(-/-) ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of macrophage colony stimulating factor. Mice with hematopoietic-specific deletion of ADAM17 have normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential.

  15. The ADAM17-amphiregulin-EGFR axis in mammary development and cancer.

    PubMed

    Sternlicht, Mark D; Sunnarborg, Susan W

    2008-06-01

    In order to fulfill its function of producing and delivering sufficient milk to newborn mammalian offspring, the mammary gland first has to form an extensive ductal network. As in all phases of mammary development, hormonal cues elicit local intra- and inter-cellular signaling cascades that regulate ductal growth and differentiation. Among other things, ductal development requires the epidermal growth factor receptor (EGFR), its ligand amphiregulin (AREG), and the transmembrane metalloproteinase ADAM17, which can cleave and release AREG from the cell surface so that it may interact with its receptor. Tissue recombination and transplantation studies demonstrate that EGFR phosphorylation and ductal development proceed only when ADAM17 and AREG are expressed on mammary epithelial cells and EGFR is present on stromal cells, and that local administration of soluble AREG can rescue the development of ADAM17-deficient transplants. Thus proper mammary morphogenesis requires the ADAM17-mediated release of AREG from ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and EGFR-dependent stromal responses that in return elicit a new set of epithelial responses, all culminating in the formation of a fully functional ductal tree. This, however, raises new issues concerning what may act upstream, downstream or in parallel with the ADAM17-AREG-EGFR axis, how it may become hijacked or corrupted during the onset and evolution of cancer, and how such ill effects may be confronted.

  16. ADAM10 as a biomarker for Alzheimer's disease: a study with Brazilian elderly.

    PubMed

    Manzine, Patricia Regina; de França Bram, Jessyka Maria; Barham, Elisabeth Joan; do Vale, Francisco de Assis Carvalho; Selistre-de-Araújo, Heloisa Sobreiro; Cominetti, Márcia Regina; Iost Pavarini, Sofia Cristina

    2013-01-01

    Alzheimer's disease (AD) is the most common cause of dementia in people above age 65. Platelet studies with ADAM10 have shown that its expression is reduced in AD patients. The aim of this research was to compare the platelet levels of ADAM10 protein in two Brazilian elderly groups, considering the stages of the disease. The SDS-PAGE technique followed by Western blotting was used. Data were analyzed using comparison, correlation and association statistical methods. The results showed reduced platelet ADAM10 levels in AD elderly compared to non-AD subjects. The disease progression intensified this reduction. ADAM10 was the only statistically significant variable (p = 0.01) to increase the AD occurrence probability. The cutoff value of 0.4212 in the receiver operating characteristic curve captured sensitivity and specificity of 70 and 80.77%, respectively. Together with other clinical criteria, ADAM10 seems to be a relevant biomarker tool for early and accurate AD diagnosis. PMID:23306532

  17. ADAM17 in tumor associated leukocytes regulates inflammatory mediators and promotes mammary tumor formation

    PubMed Central

    Chuntova, Pavlina; Brady, Nicholas J.; Witschen, Patrice M.; Kemp, Sarah E.; Nelson, Andrew C.; Walcheck, Bruce; Schwertfeger, Kathryn L.

    2016-01-01

    The presence of inflammatory cells within the tumor microenvironment has been tightly linked to mammary tumor formation and progression. Specifically, interactions between tumor cells and infiltrating macrophages can contribute to the generation of a pro-tumorigenic microenvironment. Understanding the complex mechanisms that drive tumor cell-macrophage cross-talk will ultimately lead to the development of approaches to prevent or treat early stage breast cancers. As described here, we demonstrate that the cell surface protease a disintegrin and metalloproteinase 17 (ADAM17) is expressed by macrophages in mammary tumors and contributes to regulating the expression of pro-inflammatory mediators, including inflammatory cytokines and the inflammatory mediator cyclooxygenase-2 (Cox-2). Furthermore, we demonstrate that ADAM17 is expressed on leukocytes, including macrophages, within polyoma middle T (PyMT)-derived mammary tumors. Genetic deletion of ADAM17 in leukocytes resulted in decreased onset of mammary tumor growth, which was associated with reduced expression of the Cox-2 within the tumor. These findings demonstrate that ADAM17 regulates key inflammatory mediators in macrophages and that leukocyte-specific ADAM17 is an important promoter of mammary tumor initiation. Understanding the mechanisms associated with early stage tumorigenesis has implications for the development of preventive and/or treatment strategies for early stage breast cancers.

  18. Pyrococcus Furiosus Genome Supplementary Data from the Adams Laboratory at the University of Georgia

    DOE Data Explorer

    Adams, Michael W.W.; Weinberg, Michael V.; Schut, Gerrit J.; Brehm, Scott; Datta, Susmitta; Zhou, J.

    The research in the Adams Laboratory focuses on the physiology of hyperthermophilic organisms with an emphasis on metal-containing enzymes in the hyperthermophilic marine archaeon Pyrococcus furiosus. Three of the many articles from this University of Georgia lab have supplementary materials that are available on the Adams Lab website. All three sets of data are Open Reading Frames (ORFs) used for DNA microarray experiments and the changes in signal intensities. The full citations for the three articles are: 1) Weinberg, M. V., Schut, G. J., Brehm, S., Datta, S. and Adams, M. W. W. (2005) Cold shock of a hyperthermophilic archaeon: Pyrococcus furiosus exhibits multiple responses to a suboptimal growth temperature with a key role for membrane-bound glycoproteins. J Bacteriol. 187, 336-348; 2) Schut, G. J., Brehm, S. D., Datta, S. and Adams, M. W. W. (2003) "Whole genome DNA microarray analysis of a hyperthermophile and an archaeon: Pyrococcus furiosus grown on carbohydrates or peptides" J. Bacteriol. 185, 3935-3947; Schut, G. J., Zhou, J. and Adams, M. W. W. (2001) "DNA microarray analysis of the hyperthermophilic archaeon Pyrococcus furiosus evidence for a new type of sulfur-reducing enzyme" J. Bacteriol. 183, 7027-7036. Note that these articles are copyrighted by the Journal of Bacteriology.

  19. ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands.

    PubMed

    Tanaka, Motonari; Nanba, Daisuke; Mori, Seiji; Shiba, Fumio; Ishiguro, Hiroshi; Yoshino, Koichiro; Matsuura, Nariaki; Higashiyama, Shigeki

    2004-10-01

    A disintegrin and metalloproteases (ADAMs) are implicated in the ectodomain shedding of epidermal growth factor receptor (EGFR) ligands in EGFR transactivation. However, the activation mechanisms of ADAMs remain elusive. To analyze the regulatory mechanisms of ADAM activation, we performed yeast two-hybrid screening using the cytoplasmic domain of ADAM12 as bait, and identified a protein that we designated Eve-1. Two cDNAs were cloned and characterized. They encode alternatively spliced isoforms of Eve-1, called Eve-1a and Eve-1b, that have four and five tandem Src homology 3 (SH3) domains in the carboxyl-terminal region, respectively, and seven proline-rich SH3 domain binding motifs in the amino-terminal region. The short forms of Eve-1, Eve-1c and Eve-1d, translated at Met-371 are human counterparts of mouse Sh3d19. Northern blot analysis demonstrated that Eve-1 is abundantly expressed in skeletal muscle and heart. Western blot analysis revealed the dominant production of Eve-1c in human cancer cell lines. Knockdown of Eve-1 by small interfering RNA in HT1080 cells reduced the shedding of proHB-EGF induced by angiotensin II and 12-O-tetradecanoylphorbol-13-acetate, as well as the shedding of pro-transforming growth factor-alpha, promphiregulin, and proepiregulin by 12-O-tetradecanoylphorbol-13-acetate, suggesting that Eve-1 plays a role in positively regulating the activity of ADAMs in the signaling of EGFR-ligand shedding.

  20. 50th anniversary of the discovery of ibuprofen: an interview with Dr Stewart Adams.

    PubMed

    Halford, Gayle M; Lordkipanidzé, Marie; Watson, Steve P

    2012-01-01

    2011 marks the 50th anniversary of the discovery of ibuprofen. This article is a focus on the personal reflections and career of Dr Stewart Adams OBE, the scientist whose research lead to the discovery of the cyclooxygenase inhibitor. When Dr Adams discovered ibuprofen, he was working as a pharmacologist in the Research Department for the Boots Pure Drug Company Ltd. Dr Adams was assigned to work on rheumatoid arthritis (RA) and chose in 1953 to search for a drug that would be effective in RA but would not be a corticosteroid. He was one of the first workers in this field that later became known as NSAIDs (Non-Steroidal Anti Inflammatory Drugs). In 1961, Dr Adams with John Nicholson, the organic chemist, filed a patent for the compound 2-(4-isobutylphenyl) propionic acid, later to become one of the most successful NSAIDs in the modern world, ibuprofen. In this article, Dr Adams gives his modest insight into the early stages and initial observations which led to this world-wide success.

  1. Inverse regulation of the ADAM-family members, decysin and MADDAM/ADAM19 during monocyte differentiation

    PubMed Central

    Fritsche, Jana; Müller, Alexandra; Hausmann, Martin; Rogler, Gerhard; Andreesen, Reinhard; Kreutz, Marina

    2003-01-01

    Two members of the ADAM (a disintegrin and metalloprotease)-family, MADDAM and decysin, were described as dendritic cell (DC) maturation markers. We are interested in monocyte differentiation and investigated in particular the expression pattern of both genes during the differentiation of human monocytes into DC and macrophages (MAC). Both genes are weakly expressed in freshly isolated monocytes. In immature DC decysin mRNA was absent, even after induction of the terminal differentiation of DC by CD40L or tumour necrosis factor-α (TNF-α). Only in DC maturated by lipopolysaccharide (LPS) strong signals of decysin mRNA were detected. However, MADDAM mRNA was expressed in immature DC and the expression was markedly increased after induction of the terminal DC differentiation by various stimuli. In contrast, MAC showed a high constitutive decysin mRNA expression, but expressed no MADDAM mRNA. On protein level similar results of MADDAM expression were obtained. Stimulation of MAC by LPS did not induce MADDAM mRNA expression, while decysin mRNA expression was strongly increased. Further investigations revealed that the well-known inducer of MAC differentiation, 1α,25-dihydroxyvitamin D3 up-regulated decysin mRNA expression during the differentiation of primary monocytes and myelomonocytic THP-1 cells into MAC. In vivo decysin mRNA expression was only detected in human colon, but not in other tissues we examined. Accordingly, isolated intestinal MAC expressed decysin mRNA. In conclusion, decysin and MADDAM mRNA expression were regulated in an opposite way during monocyte differentiation: MADDAM mRNA and protein was mainly detected in DC, whereas decysin mRNA expression was mainly found in MAC. Therefore only MADDAM, but not decysin is a suitable marker for human monocyte-derived DC. PMID:14632642

  2. Activity of ADAM17 (a Disintegrin and Metalloprotease 17) Is Regulated by Its Noncatalytic Domains and Secondary Structure of its Substrates*

    PubMed Central

    Stawikowska, Roma; Cudic, Mare; Giulianotti, Marc; Houghten, Richard A.; Fields, Gregg B.; Minond, Dmitriy

    2013-01-01

    ADAM proteases are implicated in multiple diseases, but no drugs based on ADAM inhibition exist. Most of the ADAM inhibitors developed to date feature zinc-binding moieties that target the active site zinc, which leads to a lack of selectivity and off target toxicity. Targeting secondary substrate binding sites (exosites) can potentially work as an alternative strategy for drug discovery; however, there are only a few reports of potential exosites in ADAM protease structures. In the study presented here, we utilized a series of TNFα-based substrates to probe ADAM10 and 17 interactions with its canonical substrate to identify the structural features that determine ADAM protease substrate specificity. We found that noncatalytic domains of ADAM17 did not directly bind the substrates used in the study but affected the binding nevertheless, most likely because of steric hindrance. Additionally, noncatalytic domains of ADAM17 affected the size/shape of the carbohydrate-binding pocket contained within the catalytic domain of ADAM17. This suggests that noncatalytic domains of ADAM17 play a role in substrate specificity and might help explain differences in substrate repertoires of ADAM17 and its closest homologue, ADAM10. We also addressed the question of which substrate features can affect ADAM protease specificity. We found that all ADAM proteases tested (i.e., ADAM10, 12, and 17) significantly decreased activity when the TNFα-derived sequence was induced into α-helical conformation, suggesting that conformation plays a role in determining ADAM protease substrate specificity. These findings can help in the discovery of ADAM isoform- and substrate-specific inhibitors. PMID:23779109

  3. Analysis of a two-bladed, teetering-hub turbine using the ADAMS (tm) software

    NASA Astrophysics Data System (ADS)

    Wright, A. D.; Osgood, R. O.; Malcolm, D. J.

    1994-05-01

    A major goal of the federal wind energy program is the rapid development and validation of structural models to determine loads and response for a wide variety of different wind turbine configurations operating under extreme conditions. Such codes are crucial to the successful design of future advanced wind turbines. In cooperation with R. Lynette & Associates the Wind Technology Division at NREL has developed a full system dynamics model of the AWT-26 Pl machine, using the Automatic Dynamic analysis of Mechanical Systems (ADAMS) software from Mechanical Dynamics, Inc. In this paper, we show validation of sub-models by comparisons with modal test data. We describe the most important system modes involved in this structure and demonstrate how the ADAMS model can be used to tune the structure to avoid interactions. We also identify questions that remain unanswered by ADAMS in modeling this turbine and recommend future directions that DOE code development activities should take.

  4. [An important son of Aub: the military surgeon and ophthalmologist Johann Adam Schmidt (1759-1809)].

    PubMed

    Krogmann, Frank; Vollmuth, Ralf

    2009-01-01

    The following article gives you a review to the life and work of the military surgeon and ophthalmologist Johann Adam Schmidt who was born in Aub/Lower Franconia on the 12th of October 1759. He had got his surgical education in Würzburg and had worked as an Unterchirurgus in the War of the Bavarian succession. Later on he completed his education in Vienna where he, by joining different work places, had been appointed to a professorship at the Medico-Surgical Joseph's Academy and became a leading figure of the Austrian military medical service. Also as an ophthalmologist Johann Adam Schmidt obtained high credit for his practical activity and his academic work. Johann Adam Schmidt died on the 19th of February 1809 and left a multiplicity of publications. He got not least publicity as the doctor of Beethoven, who dedicated the trio for piano, clarinet or violin and violoncello (Es-major) Opus 38 to Schmidt.

  5. Lytle S. Adams, DDS (1883-1970): Nonstop Airmail Pick-up inventor.

    PubMed

    Christen, Arden G; Christen, Joan A

    2005-11-01

    Between 1923 and 1940, a restless, optimistic, self-styled, inventor, Lytle S. Adams, DDS (1883-1970) was tirelessly working to develop a nonstop, airmail delivery and pick-up system. He believed that his invention would enable air postal services to serve those smaller, more isolated communities that would otherwise be bypassed due to economic and operational reasons. For 17 years, Adams vigorously promoted his pick-up system in both public and private arenas, and he even obtained congressional support for his ideas. However, he was unable to arrange for long-term, hardheaded financial and engineering support. Consequently, the once promising Adams Nonstop Airmail Pick-up System had only temporary and limited success. His endeavor, like others which came before and after, initially appeared to be a sound idea in search of inspired realization.

  6. PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells.

    PubMed

    Marchesi, Nicoletta; Amadio, Marialaura; Colombrita, Claudia; Govoni, Stefano; Ratti, Antonia; Pascale, Alessia

    2016-09-01

    Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade.

  7. PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells.

    PubMed

    Marchesi, Nicoletta; Amadio, Marialaura; Colombrita, Claudia; Govoni, Stefano; Ratti, Antonia; Pascale, Alessia

    2016-09-01

    Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade. PMID:27472877

  8. A Reader Response to File and Adams's "The Reality, Robustness, and Possible Superiority of Incidental Vocabulary Acquisition"

    ERIC Educational Resources Information Center

    Mason, Beniko; Krashen, Stephen

    2010-01-01

    File and Adams (2010) conclude that their data confirm the superiority of form-focused vocabulary instruction over incidental acquisition. The authors of this response argue that File and Adams's data actually confirm the reality, robustness, and possible superiority of incidental acquisition. Their subjects heard two passages read to them that…

  9. Problems with McAdams and Pals's (2006) Proposal of a Framework for an Integrative Theory of Personality

    ERIC Educational Resources Information Center

    Epstein, Seymour

    2007-01-01

    Comments on the original article "A New Big Five: Fundamental Principles for an Integrative Science of Personality," by Dan P. McAdams and Jennifer L. Pals (see record 2006-03947-002). Here, the current author begins with a critique of McAdams and Pals's (April 2006) five principles for a framework for an integrative theory of personality. The…

  10. 77 FR 25229 - Adams-Warnock Railway, Inc.-Lease and Operation Exemption-Norfolk Southern Railway Company

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION Surface Transportation Board Adams-Warnock Railway, Inc.--Lease and Operation Exemption-- Norfolk Southern Railway Company Adams--Warnock Railway, Inc. (AWRY), a noncarrier, has filed a verified notice...

  11. 78 FR 37791 - In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number #85993-279, CI Adams County...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... by successive Presidential Notices, the most recent being that of August 15, 2012 (77 FR 49699..., CI Adams County, Correctional Institution, P.O. Box 1600, Washington, MS 39190; Order Denying Export... Adams County, Correctional Institution, P.O. Box 1600, Washington, MS 39190, and when acting for or...

  12. 77 FR 5291 - The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... published in the Federal Register. Dated: January 20, 2012. Hillary Rodham Clinton, Secretary of State... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known as Abu Adam...

  13. Innovation and hard work: The 2015 George E. Palade Medal Award Lecture

    PubMed Central

    Whitcomb, David C.

    2015-01-01

    The George E Palade Medal is the highest honor awarded by the International Association of Pancreatology and is given to an individual who has made outstanding contributions to the understanding of the pancreas and pancreatic diseases. Professor David C Whitcomb, University of Pittsburgh, is the 2015 recipient. The Palade Lecture, presented in Shanghai, China on August 28, 2015, included 5 personal stories that provide perspective from a life-time of achievement: “My life in a nutshell”; “Two old ladies”; “7777”; “I helped put a man on the moon”; and “Rugby”. Together, the stories provide encouragement to a younger generation, struggling to find their way as physicians and scientists who are working on pancreatic or other diseases in a challenging world. PMID:26481054

  14. Innovation and hard work: The 2015 George E. Palade Medal Award Lecture.

    PubMed

    Whitcomb, David C

    2015-01-01

    The George E Palade Medal is the highest honor awarded by the International Association of Pancreatology and is given to an individual who has made outstanding contributions to the understanding of the pancreas and pancreatic diseases. Professor David C Whitcomb, University of Pittsburgh, is the 2015 recipient. The Palade Lecture, presented in Shanghai, China on August 28, 2015, included 5 personal stories that provide perspective from a life-time of achievement: "My life in a nutshell"; "Two old ladies"; "7777"; "I helped put a man on the moon"; and "Rugby". Together, the stories provide encouragement to a younger generation, struggling to find their way as physicians and scientists who are working on pancreatic or other diseases in a challenging world. PMID:26481054

  15. Innovation and hard work: The 2015 George E. Palade Medal Award Lecture.

    PubMed

    Whitcomb, David C

    2015-01-01

    The George E Palade Medal is the highest honor awarded by the International Association of Pancreatology and is given to an individual who has made outstanding contributions to the understanding of the pancreas and pancreatic diseases. Professor David C Whitcomb, University of Pittsburgh, is the 2015 recipient. The Palade Lecture, presented in Shanghai, China on August 28, 2015, included 5 personal stories that provide perspective from a life-time of achievement: "My life in a nutshell"; "Two old ladies"; "7777"; "I helped put a man on the moon"; and "Rugby". Together, the stories provide encouragement to a younger generation, struggling to find their way as physicians and scientists who are working on pancreatic or other diseases in a challenging world.

  16. Alvin C. Kraenzlein, DDS and Walter B. Tewksbury, DDS: Olympic medal winners.

    PubMed

    Christen, A G; Christen, J A

    2001-11-01

    As contemporaries, Alvin C. Kraenzlein, and Walter B. Tewksbury had a great deal in common. They were both outstanding athletic performers and each became an intercollegiate record holder in track and field. In 1898, the New York Times reported that the University of Pennsylvania "at present has the best college athletes in the world, its two particular stars being Kraenzlein and Tewksbury." As close friends and college roommates during their student years at the University of Pennsylvania College of Dentistry, these two young men graduated in close succession (Walter, 1899; Alvin, 1900). Between them, Alvin and Walter won nine Olympic medals in Paris in 1900. Ultimately, as dentists and athletes, they individually and corporately left indelible imprints on track and field for all time.

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

    PubMed

    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.

  18. ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

    PubMed

    Li, Qingyu; Zhang, Zhengyu; Li, Zengmin; Zhou, Mei; Liu, Bin; Pan, Le; Ma, Zhixing; Zheng, Yufang

    2013-01-01

    The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice. PMID:23755270

  19. ADAM17 is critical for multipolar exit and radial migration of neuronal intermediate progenitor cells in mice cerebral cortex.

    PubMed

    Li, Qingyu; Zhang, Zhengyu; Li, Zengmin; Zhou, Mei; Liu, Bin; Pan, Le; Ma, Zhixing; Zheng, Yufang

    2013-01-01

    The radial migration of neuronal progenitor cells is critical for the development of cerebral cortex layers. They go through a critical step transforming from multipolar to bipolar before outward migration. A Disintegrin and Metalloprotease 17 (ADAM17) is a transmembrane protease which can process many substrates involved in cell-cell interaction, including Notch, ligands of EGFR, and some cell adhesion molecules. In this study, we used in utero electroporation to knock down or overexpress ADAM17 at embryonic day 14.5 (E14.5) in neuronal progenitor cells to examine the role of ADAM17 in cortical embryonic neurogenesis. Our results showed that the radial migration of ADAM17-knocked down cells were normal till E16.5 and reached the intermediate zone (IZ). Then most transfected cells stopped migration and stayed at the IZ to inner cortical plate (CP) layer at E18.5, and there was higher percentage of multipolar cells at IZ layer in the ADAM17-knocked down group compared to the cells in control group. Marker staining revealed that those ADAM17-knocked down cells differentiated normally from neural stem cells (NSCs) to neuronal intermediate progenitor cells (nIPCs) but did not differentiate into mature neurons. The migration and multipolar exit defects caused by ADAM17 knockdown could be partially rescued by over-expressing an shRNA resistant ADAM17, while overexpressing ADAM17 alone did not affect the radial migration. Taken together, our results showed for the first time that, ADAM17 is critical in regulating the multipolar-stage exit and radial migration of the nIPCs during telencephalon cortex development in mice.

  20. Advances in allergen-microarray technology for diagnosis and monitoring of allergy: the MeDALL allergen-chip.

    PubMed

    Lupinek, Christian; Wollmann, Eva; Baar, Alexandra; Banerjee, Srinita; Breiteneder, Heimo; Broecker, Barbara M; Bublin, Merima; Curin, Mirela; Flicker, Sabine; Garmatiuk, Tetiana; Hochwallner, Heidrun; Mittermann, Irene; Pahr, Sandra; Resch, Yvonne; Roux, Kenneth H; Srinivasan, Bharani; Stentzel, Sebastian; Vrtala, Susanne; Willison, Leanna N; Wickman, Magnus; Lødrup-Carlsen, Karin C; Antó, Josep Maria; Bousquet, Jean; Bachert, Claus; Ebner, Daniel; Schlederer, Thomas; Harwanegg, Christian; Valenta, Rudolf

    2014-03-01

    Allergy diagnosis based on purified allergen molecules provides detailed information regarding the individual sensitization profile of allergic patients, allows monitoring of the development of allergic disease and of the effect of therapies on the immune response to individual allergen molecules. Allergen microarrays contain a large variety of allergen molecules and thus allow the simultaneous detection of allergic patients' antibody reactivity profiles towards each of the allergen molecules with only minute amounts of serum. In this article we summarize recent progress in the field of allergen microarray technology and introduce the MeDALL allergen-chip which has been developed for the specific and sensitive monitoring of IgE and IgG reactivity profiles towards more than 170 allergen molecules in sera collected in European birth cohorts. MeDALL is a European research program in which allergen microarray technology is used for the monitoring of the development of allergic disease in childhood, to draw a geographic map of the recognition of clinically relevant allergens in different populations and to establish reactivity profiles which are associated with and predict certain disease manifestations. We describe technical advances of the MeDALL allergen-chip regarding specificity, sensitivity and its ability to deliver test results which are close to in vivo reactivity. In addition, the usefulness and numerous advantages of allergen microarrays for allergy research, refined allergy diagnosis, monitoring of disease, of the effects of therapies, for improving the prescription of specific immunotherapy and for prevention are discussed.

  1. Rethinking Equality of Opportunity: Comment on Adam Swift's "How Not to Be a Hypocrite"

    ERIC Educational Resources Information Center

    Anderson, Elizabeth

    2004-01-01

    Adam Swift objects to private schools on the grounds of equal opportunity and efficiency, and to both private and selective public schools on the grounds of solidarity and improving the academic achievement of less advantaged students. I argue that private schools are not inefficient, and that a meritocratic ideal of equality of opportunity in…

  2. VizieR Online Data Catalog: ADAM: 3D asteroid shape reconstruction code (Viikinkoski+, 2015)

    NASA Astrophysics Data System (ADS)

    Viikinkoski, M.; Kaasalainen, M.; Durech, J.

    2015-02-01

    About the code: ADAM is a collection of routines for 3D asteroid shape reconstruction from disk-resolved observations. Any combination of lightcurves, adaptive optics images, HST/FGS data, range-Doppler radar images and disk-resolved thermal images may be used as data sources. The routines are implemented in a combination of MATLAB and C. (2 data files).

  3. Adam Smith and the Educative Critique: A Response to My Commentators

    ERIC Educational Resources Information Center

    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…

  4. THE E.O.A. BASIC EDUCATION COMMUNITY IN JOHN ADAMS ADULT SCHOOL, 1965-1966.

    ERIC Educational Resources Information Center

    EDMINSTER, HOWARD

    DATA FROM THE DEPARTMENT OF SOCIAL SERVICES AND SCHOOL FILES ARE PRESENTED ON 99 STUDENTS (90 PERCENT) REFERRED BY THE AGENCY TO THE BASIC EDUCATION PROGRAM AT THE JOHN ADAMS ADULT SCHOOL. OVER 60 PERCENT WERE NEGROES, WITH WHITES, MEXICANS, AND AMERICAN INDIANS ALSO REPRESENTED. THE MAJORITY WERE FROM SOUTHERN STATES, 37 PERCENT WERE DIVORCED OR…

  5. Music for Elementary Teachers; Self-Help Guide (MUS 370). Adams State College.

    ERIC Educational Resources Information Center

    Stokes, Cloyce

    This self-help guide for the music teacher is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The guide itself consists of 11 modules, the first five of which focus on the mathematical and scientific aspects of music--pitch, tempo, furation, time, and key. These five modules are…

  6. Keywords and Vocabulary Acquisition: Some Words of Caution about Johnson, Adams, and Bruning (1985).

    ERIC Educational Resources Information Center

    Pressley, Michael; Levin, Joel R.

    1985-01-01

    The mnemonic keyword study of Johnson, Adams, and Bruning (1985) on effectiveness of the keyword method for second-language vocabulary acquisition is critiqued. Of particular concern are literature currency vis-a-vis the authors' stated rationale for conducting the study, and methodological issues associated with the study's implementation.…

  7. Every Day Is Earth Day: A Resource List from the James P. Adams Library.

    ERIC Educational Resources Information Center

    Brennan, Patricia B. M.; And Others

    This is an extensive interdisciplinary bibliography of environmentally-related resources from the shelves of the James P. Adams Library at Rhode Island College. It is noted that the list is selective rather than comprehensive, and that the regional (United States, New England, or Rhode Island) has been emphasized when possible. The bibliography…

  8. Award for Distinguished Scientific Early Career Contributions to Psychology: Adam K. Anderson

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Adam K. Anderson, recipient of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for his outstanding contribution to understanding the representation of emotion and its influence on cognition. By combining psychological and neuroscience techniques with rigorous and creative experimental designs, Anderson has…

  9. Boundary Value Technique for Initial Value Problems Based on Adams-Type Second Derivative Methods

    ERIC Educational Resources Information Center

    Jator, S. N.; Sahi, R. K.

    2010-01-01

    In this article, we propose a family of second derivative Adams-type methods (SDAMs) of order up to 2k + 2 ("k" is the step number) for initial value problems. The methods are constructed through a continuous approximation of the SDAM which is obtained by multistep collocation. The continuous approximation is used to obtain initial value methods,…

  10. Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

    ERIC Educational Resources Information Center

    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)

  11. Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

    ERIC Educational Resources Information Center

    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)

  12. How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

    ERIC Educational Resources Information Center

    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…

  13. Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

    ERIC Educational Resources Information Center

    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)

  14. Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

    ERIC Educational Resources Information Center

    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)

  15. Implementation of Distributed ADAMS Over Legion Using a Component DBMS Design. Final Report

    SciTech Connect

    Pfaltz, John L.; Orlandic, Ratko

    2002-11-26

    There were four primary research areas reported in the final report for the original funding period They are: implementation of high dimensional data spaces; knowledge discovery in scientific databases; and mismatch between implementing components; demonstrate the utility of ADAMS in a specific domain science.

  16. The sheddase ADAM10 is a potent modulator of prion disease

    PubMed Central

    Altmeppen, Hermann C; Prox, Johannes; Krasemann, Susanne; Puig, Berta; Kruszewski, Katharina; Dohler, Frank; Bernreuther, Christian; Hoxha, Ana; Linsenmeier, Luise; Sikorska, Beata; Liberski, Pawel P; Bartsch, Udo; Saftig, Paul; Glatzel, Markus

    2015-01-01

    The prion protein (PrPC) is highly expressed in the nervous system and critically involved in prion diseases where it misfolds into pathogenic PrPSc. Moreover, it has been suggested as a receptor mediating neurotoxicity in common neurodegenerative proteinopathies such as Alzheimer's disease. PrPC is shed at the plasma membrane by the metalloprotease ADAM10, yet the impact of this on prion disease remains enigmatic. Employing conditional knockout mice, we show that depletion of ADAM10 in forebrain neurons leads to posttranslational increase of PrPC levels. Upon prion infection of these mice, clinical, biochemical, and morphological data reveal that lack of ADAM10 significantly reduces incubation times and increases PrPSc formation. In contrast, spatiotemporal analysis indicates that absence of shedding impairs spread of prion pathology. Our data support a dual role for ADAM10-mediated shedding and highlight the role of proteolytic processing in prion disease. DOI: http://dx.doi.org/10.7554/eLife.04260.001 PMID:25654651

  17. Springs, streams, and gas vent on and near Mount Adams volcano, Washington

    USGS Publications Warehouse

    Nathenson, Manuel; Mariner, Robert H.

    2013-01-01

    Springs and some streams on Mount Adams volcano have been sampled for chemistry and light stable isotopes of water. Spring temperatures are generally cooler than air temperatures from weather stations at the same elevation. Spring chemistry generally reflects weathering of volcanic rock from dissolved carbon dioxide. Water in some springs and streams has either dissolved hydrothermal minerals or has reacted with them to add sulfate to the water. Some samples appear to have obtained their sulfate from dissolution of gypsum while some probably involve reaction with sulfide minerals such as pyrite. Light stable isotope data for water from springs follow a local meteoric water line, and the variation of isotopes with elevation indicate that some springs have very local recharge and others have water from elevations a few hundred meters higher. No evidence was found for thermal or slightly thermal springs on Mount Adams. A sample from a seeping gas vent on Mount Adams was at ambient temperature, but the gas is similar to that found on other Cascade volcanoes. Helium isotopes are 4.4 times the value in air, indicating that there is a significant component of mantle helium. The lack of fumaroles on Mount Adams and the ambient temperature of the gas indicates that the gas is from a hydrothermal system that is no longer active.

  18. Highlighting High Performance Buildings: Adam Joseph Lewis Center for Environmental Studies

    SciTech Connect

    2002-11-01

    Oberlin College's Adam Joseph Lewis Center for Environmental Studies is a high-performance building featuring an expansive photovoltaic system and a closed-loop groundwater heat pump system. Designers incorporated energy-efficient components and materials that are local, non-toxic, and durable.

  19. Financial Assistance to Black Doctoral Students in Two "Adams" States: A Policy Analysis.

    ERIC Educational Resources Information Center

    Upton, James N.; Pruitt, Anne S.

    The context for financial aid policy affecting black doctoral students in Oklahoma and Florida was studied using the case study method. Attention was focused on environmental and organizational variables affecting the implementation of financial aid policy. Historical patterns surrounding race relations in both states before the 1973 "Adams"…

  20. Serendipity in the Theater: Maude Adams as James M. Barrie's American Muse.

    ERIC Educational Resources Information Center

    Diaz de Chumaceiro, Cora L.

    2003-01-01

    This essay discusses how Maude Adams influenced James M. Barrie's creative process and became his inspiration. Set change theory is underscored as a cognitive explanation for Barrie's illumination. The psychoanalytic theory of transference is proposed as an underlying mechanism for facilitating the change of mental set during the incubation stage.…

  1. Working for the People? Mrs Bridges Adams and the London School Board, 1897-1904.

    ERIC Educational Resources Information Center

    Martin, Jane

    2000-01-01

    Focuses on Mrs. Bridges Adams who was a supporter of state maintenance committed to educational opportunity for workers' children. Focuses on her political recruitment, her contribution to the work of the London School Board (England), and her role in the struggle to save the school board system. (CMK)

  2. Higher Education Financing in the Fifty States: Significance for the 'Adams' States.

    ERIC Educational Resources Information Center

    Budig, Jeanne E.; Khan, Anwar

    Findings of a study on higher education financing in the states are summarized with specific reference for the states covered by the 1977 Adams versus Richardson decision. The study, "Higher Education Financing in the Fifty States: Interstate Comparisons" (Marilyn McCoy, D. Kent Halstead), was jointly issued by the National Center for Higher…

  3. Black Faculty in Traditionally White Institutions in Selected "Adams" States: Characteristics, Experiences and Perceptions.

    ERIC Educational Resources Information Center

    Silver, John H.; And Others

    This document provides an empirical analysis of the hiring, promotion/advancement, and retention of black faculty in traditionally white public institutions of higher education in the 10 states affected by the Adams v. Richardson case. The underrepresentation of black scholars on the faculties of the nation's colleges and universities remains a…

  4. Achieving Social Justice: An Examination of Oklahoma's Response to "Adams v. Richardson."

    ERIC Educational Resources Information Center

    Olson, Carol; Hagy, Joe

    1990-01-01

    Reviews the efforts of Oklahoma to comply with the 1969 Supreme Court decision, "Adams v Richardson," which required states to desegregate traditionally White educational institutions. Concludes that Oklahoma has failed to increase the number of minority students in institutions of higher education but has institutionalized the principles of…

  5. The Quest To Define Collegiate Desegregation: Black Colleges, Title VI Compliance, and Post-Adams Litigation.

    ERIC Educational Resources Information Center

    Brown, M. Christopher, II

    This book outlines and explains the statutory and legal foundations of desegregation in higher education. It traces the historical development of college desegregation and analyzes the history of compliance and enforcement litigation in the aftermath of "Adams v. Richardson" (1972). The chapters are: (1) "Black Colleges and Desegregation"; (2)…

  6. Fractional Adams-Bashforth/Moulton methods: An application to the fractional Keller-Segel chemotaxis system

    NASA Astrophysics Data System (ADS)

    Zayernouri, Mohsen; Matzavinos, Anastasios

    2016-07-01

    We first formulate a fractional class of explicit Adams-Bashforth (A-B) and implicit Adams-Moulton (A-M) methods of first- and second-order accuracy for the time-integration of 0 CD t τ u (x , t) = g (t ; u), τ ∈ (0 , 1 ], where 0 CD t τ denotes the fractional derivative in the Caputo sense. In this fractional setting and in contrast to the standard Adams methods, an extra history load term emerges and the associated weight coefficients are τ-dependent. However when τ = 1, the developed schemes reduce to the well-known A-B and A-M methods with standard coefficients. Hence, in terms of scientific computing, our approach constitutes a minimal modification of the existing Adams libraries. Next, we develop an implicit-explicit (IMEX) splitting scheme for linear and nonlinear fractional PDEs of a general advection-reaction-diffusion type, and we apply our scheme to the time-space fractional Keller-Segel chemotaxis system. In this context, we evaluate the nonlinear advection term explicitly, employing the fractional A-B method in the prediction step, and we treat the corresponding diffusion term implicitly in the correction step using the fractional A-M scheme. Moreover, we perform the corresponding spatial discretization by employing an efficient and spectrally-accurate fractional spectral collocation method. Our numerical experiments exhibit the efficiency of the proposed IMEX scheme in solving nonlinear fractional PDEs.

  7. "Beginning To Read: Thinking and Learning about Print" by Marilyn Jager Adams. A Summary.

    ERIC Educational Resources Information Center

    Stahl, Steven A.; And Others

    Prepared for teachers, school administrators, parents, and other members of the interested public, this summary of Marilyn Jager Adams'"Beginning to Read: Thinking and Learning about Print" selects from the complex and extensive body of research in the book to present a more direct but much less detailed account of useful, research-based…

  8. The emerging role of matrix metalloproteases of the ADAM family in male germ cell apoptosis

    PubMed Central

    Urriola-Muñoz, Paulina; Lagos-Cabré, Raúl

    2011-01-01

    Constitutive germ cell apoptosis during mammalian spermatogenesis is a key process for controlling sperm output and to eliminate damaged or unwanted cells. An increase or decrease in the apoptosis rate has deleterious consequences and leads to low sperm production. Apoptosis in spermatogenesis has been widely studied, but the mechanism by which it is induced under physiological or pathological conditions has not been clarified. We have recently identified the metalloprotease ADAM17 (TACE) as a putative physiological inducer of germ cell apoptosis. The mechanisms involved in regulating the shedding of the ADAM17 extracellular domain are still far from being understood, although they are important in order to understand cell-cell communications. Here, we review the available data regarding apoptosis during mammalian spermatogenesis and the localization of ADAM proteins in the male reproductive tract. We propose an integrative working model where ADAM17, p38 MAPK, protein kinase C (PKC) and the tyrosine kinase c-Abl participate in the physiological signalling cascade inducing apoptosis in germ cells. In our model, we also propose a role for the Sertoli cell in regulating the Fas/FasL system in order to induce the extrinsic pathway of apoptosis in germ cells. This working model could be applied to further understand constitutive apoptosis in spermatogenesis and in pathological conditions (e.g., varicocele) or following environmental toxicants exposure (e.g., genotoxicity or xenoestrogens). PMID:22319668

  9. The Life and Times of John Couch Adams, from 1819 to 1847

    NASA Astrophysics Data System (ADS)

    Sheen, Brian M.

    2011-01-01

    John Couch Adams was born in 1819 in the middle of Cornwall, the most remote and isolated county in England. How he progressed from there to Cambridge University to become one of the finest mathematicians of the nineteenth century fills everyone who studies him with awe. Tragically what should have been his greatest triumph - the discovery of a new planet - was marred by mishap, controversy and unanswered questions. This presentation examines one of the first of these questions and provides new answers based on recently revealed evidence. The Astronomer Royal of the day was attempting to support Adams and as part of that support asked if his analysis took into account changes in radius vector of Uranus. Adams did not reply and the rest as they say is history. However there is far more to the question than a non-existent letter - this in itself turns out to be not exactly true. Further analysis of the orbits and a letter in French - not been translated before reveals Adams had a more profound understanding of the situation than some later authors have given him credit.

  10. Making Socialists: Mary Bridges Adams and the Fight for Knowledge and Power, 1855-1939

    ERIC Educational Resources Information Center

    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, "Women and…

  11. Comparison of different order Adams-Bashforth methods in an atmospheric general circulation model

    NASA Astrophysics Data System (ADS)

    Zhao, Bin; Zhang, Bo

    2011-12-01

    The Asselin-Robert time filter used in the leapfrog scheme does degrade the accuracy of calculations. As an attractive alternative to leapfrog time differencing, the second-order Adams-Bashforth method is not subject to time splitting instability and keeps excellent calculation accuracy. A second-order Adams-Bashforth model has been developed, which represents better stability, excellent convergence and improved simulation of prognostic variables. Based on these results, the higher-order Adams-Bashforth methods are developed on the basis of NCAR (National Center for Atmospheric Research) CAM 3.1 (Community Atmosphere Model 3.1) and the characteristics of dynamical cores are analyzed in this paper. By using Lorenz nonlinear convective equations, the filtered leapfrog scheme shows an excellent pattern for eliminating 2Δ t wave solutions after 20 steps but represents less computational solution accuracy. The fourth-order Adams-Bashforth method is closely converged to the exact solution and provides a reference against which other methods may be compared. Thus, the Adams-Bashforth methods produce more accurate and convergent solution with differencing order increasing. The Held-Suarez idealized test is carried out to demonstrate that all methods have similar climate states to the results of many other global models for long-term integration. Besides, higher-order methods perform better in mass conservation and exhibit improvement in simulating tropospheric westerly jets, which is likely equivalent to the advantages of increasing horizontal resolutions. Based on the idealized baroclinic wave test, a better capability of the higher-order method in maintaining simulation stability is convinced. Furthermore, after the baroclinic wave is triggered through overlaying the steady-state initial conditions with the zonal perturbation, the higher-order method has a better ability in the simulation of baroclinic wave perturbation.

  12. Dysfunctional ADAM22 implicated in progressive encephalopathy with cortical atrophy and epilepsy

    PubMed Central

    Muona, Mikko; Fukata, Yuko; Anttonen, Anna-Kaisa; Laari, Anni; Palotie, Aarno; Pihko, Helena; Lönnqvist, Tuula; Valanne, Leena; Somer, Mirja; Fukata, Masaki

    2016-01-01

    Objective: To identify the molecular genetic basis of a syndrome characterized by rapidly progressing cerebral atrophy, intractable seizures, and intellectual disability. Methods: We performed exome sequencing in the proband and whole-genome single nucleotide polymorphism genotyping (copy number variant analysis) in the proband-parent trio. We used heterologous expression systems to study the functional consequences of identified mutations. Results: The search for potentially deleterious recessive or de novo variants yielded compound heterozygous missense (c.1202G>A, p.Cys401Tyr) and frameshift deletion (c.2396delG, p.Ser799IlefsTer96) mutations in ADAM22, which encodes a postsynaptic receptor for LGI1. The deleterious effect of the mutations was observed in cell surface binding and immunoprecipitation assays, which revealed that both mutant proteins failed to bind to LGI1. Furthermore, immunoprecipitation assays showed that the frameshift mutant ADAM22 also did not bind to the postsynaptic scaffolding protein PSD-95. Conclusions: The mutations identified abolish the LGI1-ADAM22 ligand-receptor complex and are thus a likely primary cause of the proband's epilepsy syndrome, which is characterized by unusually rapidly progressing cortical atrophy starting at 3–4 months of age. These findings are in line with the implicated role of the LGI1-ADAM22 complex as a key player in nervous system development, specifically in functional maturation of postnatal synapses. Because the frameshift mutation affects an alternatively spliced exon with highest expression in postnatal brain, the combined effect of the mutations is likely to be hypomorphic rather than complete loss of function. This is compatible with the longer survival of the patient compared to Lgi1−/− and Adam22−/− mice, which develop lethal seizures during the first postnatal weeks. PMID:27066583

  13. Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

    NASA Technical Reports Server (NTRS)

    Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

    2012-01-01

    NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the

  14. Association of ADAM33 gene polymorphisms with COPD in a northeastern Chinese population

    PubMed Central

    2009-01-01

    Background Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China. Methods A total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study. Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results Statistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P < 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61; P < 0.001, OR = 2.60, 95% CI = 2.06-3.30; P = 0.03, OR = 1.31, 95% CI = 1.02-1.69; and P < 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively). Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P = 0.0002, 0.0001, 0.0005, and 0.0074, respectively). In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P < 0.0001). Conclusion These preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population. PMID:20003279

  15. An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.

    PubMed

    Atapattu, Lakmali; Saha, Nayanendu; Chheang, Chanly; Eissman, Moritz F; Xu, Kai; Vail, Mary E; Hii, Linda; Llerena, Carmen; Liu, Zhanqi; Horvay, Katja; Abud, Helen E; Kusebauch, Ulrike; Moritz, Robert L; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M; Nikolov, Dimitar B; Lackmann, Martin; Janes, Peter W

    2016-08-22

    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

  16. MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

    SciTech Connect

    Shan, Nianxi; Shen, Liangfang; Wang, Jun; He, Dan; Duan, Chaojun

    2015-01-02

    Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues and cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.

  17. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.

    PubMed

    Takayanagi, Takehiko; Forrester, Steven J; Kawai, Tatsuo; Obama, Takashi; Tsuji, Toshiyuki; Elliott, Katherine J; Nuti, Elisa; Rossello, Armando; Kwok, Hang Fai; Scalia, Rosario; Rizzo, Victor; Eguchi, Satoru

    2016-10-01

    Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications.

  18. Src plays a key role in ADAM28 expression in v-src-transformed epithelial cells and human carcinoma cells.

    PubMed

    Abe, Hitoshi; Mochizuki, Satsuki; Ohara, Kentaro; Ueno, Mari; Ochiai, Hiroki; Kitagawa, Yuko; Hino, Okio; Sato, Hiroshi; Okada, Yasunori

    2013-11-01

    ADAM28, a disintegrin and metalloproteinase 28, is overexpressed by carcinoma cells with direct correlations with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, the molecular mechanisms of ADAM28 gene expression in carcinoma cells remain elusive. Herein, we investigated the expression of ADAM28 in Madin-Darby canine kidney epithelial cells transformed by oncogenes, including v-src, LMP1, ErbB2, Ha-Ras, and c-Fos, and found that v-src transformants selectively induce ADAM28. Implantation of the v-src transformants showed a progressively growing tumor, which was significantly suppressed by local injections of anti-ADAM28 antibody. ADAM28 expression in v-src transformants was partially inhibited by treatment with inhibitors to Src kinase, mitogen-activated protein kinase kinase (MEK), phosphatidylinositol 3-kinase (PI3K), or mammalian target of rapamycin, and abrogated by v-Src kinase inhibitor, radicicol, or a mixture of MEK and PI3K inhibitors. Human carcinoma cell lines of the lung, breast, ovary, kidney, and colon showed ADAM28 expression, which was correlated with phosphorylation of c-Src and suppressed by the inhibitors in a similar way to v-src transformants. IHC of the human tumor tissues demonstrated co-expression of ADAM28 and phosphorylated Src in neoplastic cells of the breast, lung, and colon carcinomas and some adenomas of the colon, but not in nonneoplastic colon mucosa. Our data provide, to the best of our knowledge, the first evidence that Src is an inducer of ADAM28 gene expression through the MEK/extracellular signal-regulated kinase and PI3K/mammalian target of rapamycin pathways. PMID:24007880

  19. Vascular ADAM17 as a Novel Therapeutic Target in Mediating Cardiovascular Hypertrophy and Perivascular Fibrosis Induced by Angiotensin II.

    PubMed

    Takayanagi, Takehiko; Forrester, Steven J; Kawai, Tatsuo; Obama, Takashi; Tsuji, Toshiyuki; Elliott, Katherine J; Nuti, Elisa; Rossello, Armando; Kwok, Hang Fai; Scalia, Rosario; Rizzo, Victor; Eguchi, Satoru

    2016-10-01

    Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure and enhances cardiovascular remodeling and damage may be distinct. However, the signal transduction cascade by which AngII specifically initiates cardiovascular remodeling, such as hypertrophy and fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, which may be responsible for cardiovascular remodeling but not hypertension induced by AngII. Thus, the objective of this study was to test the hypothesis that activation of vascular ADAM17 is indispensable for vascular remodeling but not for hypertension induced by AngII. Vascular ADAM17-deficient mice and control mice were infused with AngII for 2 weeks. Control mice infused with AngII showed cardiac hypertrophy, vascular medial hypertrophy, and perivascular fibrosis. These phenotypes were prevented in vascular ADAM17-deficient mice independent of blood pressure alteration. AngII infusion enhanced ADAM17 expression, epidermal growth factor receptor activation, and endoplasmic reticulum stress in the vasculature, which were diminished in ADAM17-deficient mice. Treatment with a human cross-reactive ADAM17 inhibitory antibody also prevented cardiovascular remodeling and endoplasmic reticulum stress but not hypertension in C57Bl/6 mice infused with AngII. In vitro data further supported these findings. In conclusion, vascular ADAM17 mediates AngII-induced cardiovascular remodeling via epidermal growth factor receptor activation independent of blood pressure regulation. ADAM17 seems to be a unique therapeutic target for the prevention of hypertensive complications. PMID:27480833

  20. On the importance of debate in (geo-)scientific research (Arthur Holmes Medal Lecture)

    NASA Astrophysics Data System (ADS)

    Courtillot, V.

    2012-04-01

    It is of course a great honor to receive the Holmes medal from EGU. As past (founding) treasurer and later president of EUG, the medal carries special significance for me. It may be a good time to look back on the scientific path I have followed, pursuing research in the geosciences, with outstanding support from a number of family members (foremost my wife Michèle), mentors, colleagues and students. Chance, not planning, led me to attend a French school that trained mining engineers, then a US University that made me fall in love with geophysics and plate tectonics at a time when this scientific revolution was still going on, and finally the marvelous Institut de Physique du Globe de Paris (IPGP), where I have spent the rest of my career to this day. To pursue on this path, I selected the rather separate fields of paleomagnetism (then linked to geology) and geomagnetism (then linked to physics). I have devoted much of my time to make sure that the two specialties would closely interact, including in the structure of our groups at IPGP. Geo- and paleo-magnetism have turned out (in a way reminiscent of geochemistry) to be powerful tools to explore a broad range of exciting scientific questions. Equipped with them, I have had the pleasure and good fortune to navigate from the discovery of geomagnetic secular variation impulses (with Jean-Louis Le Mouël), now inelegantly called "geomagnetic jerks", to that of propagating rifting of continents in the Afar depression, to fascinating work on the India-Asia collision in the Tibetan plateau and the Cenozoic paleogeography of the Indian ocean bordering continents, to the reconstruction of synthetic apparent polar wander paths for major continental masses (with Jean Besse) that have been widely used, to the understanding of the significance of the volume, age and short duration of massive flood basalt volcanism in the Deccan traps of India and their potential link to the biological mass extinction at the Cretaceous