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Sample records for nuclear association david

  1. 78 FR 60273 - David E. Cereghino, Idaho County Light & Power Cooperative Association, Inc.; Notice of Transfer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... Association, Inc.; Notice of Transfer of Exemption 1. By letter filed March 25, 2011, David E. Cereghino and Idaho County Light & Power Cooperative Association, Inc. informed the Commission that the exemption from... transferred to Idaho County Light & Power Cooperative Association, Inc. The project is located on John...

  2. Interview with David Moore

    ERIC Educational Resources Information Center

    Rossman, Allan; Dietz, E. Jacquelin; Moor, David

    2013-01-01

    David Moore is Professor Emeritus of Statistics at Purdue University. He served as the first President of the International Association for Statistical Education (IASE) from 1993-1995 and as President of the American Statistical Association (ASA) in 1998. He is a Fellow of the ASA and of the IMS and was awarded the ASA's Founders Award in…

  3. David Gale: Restless Pioneer

    ERIC Educational Resources Information Center

    Meyer, Walter

    2006-01-01

    David Gale was one of the mathematicians responsible for the modern form of the theory of duality in linear programming and the associated proof of the minimax theorem in the theory of games. He is a member of the National Academy of Sciences and is Professor Emeritus of Mathematics and Operations Research at the University of California at…

  4. David Hartley's Newtonian neuropsychology.

    PubMed

    Smith, C U

    1987-04-01

    David Hartley's association psychology has been immensely influential. His vibrationist neurophysiology has, in contrast, been largely overlooked and forgotten. Hartley's vibration theory is examined. On the one hand it is shown how closely it is related to Sir Isaac Newton's mathematical physics and on the other how well it complements the association theory. The vibration theory, indeed, strongly influenced Hartley's associationist psychology and hence is of more than merely antiquarian interest. Although Hartley's understanding of the central nervous system has long been superseded, his general ideas prefigure some aspects of contemporary neurophysiology and philosophy of mind and thus provide a further reason for rescuing his vibrationism from oblivion.

  5. Remembering David N. Schramm

    NASA Astrophysics Data System (ADS)

    Turner, Michael S.

    2001-03-01

    Eight months ago David Schramm died doing one of things he loved most - flying his airplane, known as Big-bang Aviation. He was to have been at this meeting doing something that he loved even more - going to scientific meetings to talk about the latest results and to renew friendships...

  6. David Keynes Hill.

    PubMed

    Huxley, Andrew

    2003-01-01

    David Hill followed his father, A.V. Hill FRS, into the study of muscular contraction. Using a wide range of experimental techniques, he made several important advances of which the most important was the discovery of the 'short-range elastic component', a phenomenon which implied that even in the resting state there was an interaction between the thick (myosin) and thin (actin) filaments. He also studied physical changes in nerve when stimulated.

  7. David Baines: Rural Doctor, Lecturer, Dancer.

    ERIC Educational Resources Information Center

    Wisecarver, Charmaine

    1993-01-01

    Discusses the career of David Baines, an American Indian doctor who successfully integrates traditional and modern medicine. Describes problems faced by American Indian doctors, the tremendous amount of work involved in medical training, and problems associated with working in rural areas and trying to straddle two opposing cultures when…

  8. Obituary: David Stanley Evans, 1916-2004

    NASA Astrophysics Data System (ADS)

    Bash, Frank N.

    2005-12-01

    headquartered in Cape Town, South Africa. David had designed and built a Newtonian spectrograph for the 74-inch Radcliffe Telescope with which he measured the first southern galaxy redshifts. David and his family spent 1965-66 in Austin, Texas, where he was a National Science Foundation Senior Visiting Scientist at the University of Texas and McDonald Observatory. They moved permanently to Austin in 1968 and David became a Professor of Astronomy and Associate Director of McDonald Observatory at the University of Texas at Austin. At McDonald Observatory, R. E. Nather had devised a high-speed photometer capable of measuring millisecond time-scale changes in brightness and with Brian Warner, he invented "high-speed astronomy". This instrument caused Evans to revive his occultation program and, over the next twenty years, he produced the major part of the angular diameters of late-type stars with his students and collaborators. In addition, David and collaborators used the extensive collections of the University of Texas to write "Herschel at the Cape". David was also involved in observing the occultation of ? Sco by Jupiter in 1972 and in observing, during a solar eclipse in 1973, the gravitational deflections in the positions of stars whose light passes near to the Sun. The eclipse was observed from Mauritania, and the observations confirmed Einstein's prediction again. David Evans and his students studied late-type stars that have large star-spots and others that flare. In addition, they studied stars whose lunar occultation observations had revealed them to be double or even more than two stars. David Evans's major scientific contribution was an application of his stellar angular diameters to deduce the surface brightness of stars with the result that with suitable color indices one could use photometry to deduce the angular diameter of stars. This is applicable to stars which can never be occulted by the Moon, and its application to Cepheid variable stars has yielded their

  9. David Crighton 1942 2000

    NASA Astrophysics Data System (ADS)

    Ffowcs Williams, John E.

    2001-06-01

    David Crighton was struck down by cancer in his fifty-eighth year. He was then at the height of his career and was one of the most admired personalities in fluid mechanics. He had specialized in wave theory, helping to understand and solve problems of practical importance using the full power of mathematical method. Efforts to control the sound and vibration caused by unsteady flow were never far from his thinking, and Crighton's contribution to those efforts has changed significantly the way the subject is viewed. Having first attracted him into the field and never losing my interest in the way he was influencing it, it is natural that I should comment on the technical developments while looking back on Crighton's professional life. The subject has changed a great deal and there are now many more researchers involved in its study, many of whom rely on techniques that Crighton pioneered really powerful mathematical methods. But the basic problems remain: powerful flows are noisy.

  10. David Morrison on Lake Vostok

    NASA Video Gallery

    Dr. David Morrison discusses the implications of research possibilities at Lake Vostok, one of the largest subglacial lakes located over two miles beneath the ice in Antarctica. The lake has been c...

  11. Memories of David Kirzhnits

    NASA Astrophysics Data System (ADS)

    Bolotovsky, B. M.

    2013-06-01

    In the mid-1950s, a new staff member appeared at the Theory Division of the Physical Institute of the Academy of Sciences (FIAN): David Abramovich Kirzhnits. A Moscow State University alumnus, after graduation he had been assigned to a large defense plant in the city of Gorky, where he had worked for several years as an engineer. He was "liberated" from there by Igor Evgenyevich Tamm, our department head, who managed to transfer him to FIAN. Igor Evgenyevich knew D. A. Kirzhnits - they had met in Moscow before Kirzhnits finished university. At that time Kirzhnits was performing thesis work with professor A. S. Kompaneyets as academic adviser. At his adviser's suggestion, D. Kirzhnits consulted with I. E. Tamm on questions pertaining to the thesis topic. I. E. Tamm took a great liking for the diploma student, and he even wanted to recruit D. A. Kirzhnits for the Theory Division immediately after graduation. But at that time (1949) this proved impossible for several reasons. First, D. Kirzhnits was, as they say, an "invalid of the fifth group" - a Jew - which during those years of violent struggle against cosmopolitanismb often proved an obstacle in looking for work. Second, during the years of mass repressions D. Kirzhnits' father had been arrested on treason charges (according to the charges, he had wanted to sell the Far East to Japan). After intensive investigation his father was released, but he lived only a little longer. Reports of this also could have impeded his acceptance. Third, Igor Evgenyevich didn't have enough weight in officials' eyes at that time and so was unable to overcome "first" and "second."...

  12. Hydrologic issues associated with nuclear waste repositories

    NASA Astrophysics Data System (ADS)

    Tsang, Chin-Fu; Neretnieks, Ivars; Tsang, Yvonne

    2015-09-01

    Significant progress in hydrology, especially in subsurface flow and solute transport, has been made over the last 35 years because of sustained interest in underground nuclear waste repositories. The present paper provides an overview of the key hydrologic issues involved, and to highlight advances in their understanding and treatment because of these efforts. The focus is not on the development of radioactive waste repositories and their safety assessment, but instead on the advances in hydrologic science that have emerged from such studies. Work and results associated with three rock types, which are being considered to host the repositories, are reviewed, with a different emphasis for each rock type. The first rock type is fractured crystalline rock, for which the discussion will be mainly on flow and transport in saturated fractured rock. The second rock type is unsaturated tuff, for which the emphasis will be on flow from the shallow subsurface through the unsaturated zone to the repository. The third rock type is clay-rich formations, whose permeability is very low in an undisturbed state. In this case, the emphasis will be on hydrologic issues that arise from mechanical and thermal disturbances; i.e., on the relevant coupled thermo-hydro-mechanical processes. The extensive research results, especially those from multiyear large-scale underground research laboratory investigations, represent a rich body of information and data that can form the basis for further development in the related areas of hydrologic research.

  13. David Hume on Competent Judges

    ERIC Educational Resources Information Center

    Eaton, Marcia Muelder

    2004-01-01

    This essay is the eighth in an occasional series on past treatments of major issues in arts education policy from antiquity through the twentieth century. The essay on which it is based, David Hume's "Of the Standard of Taste," originally published in 1757, is too extensive to be reprinted here, but it is easily accessible in the public domain.…

  14. [Movement disorders in David Copperfield].

    PubMed

    Garćia Ruiz, P J; Gulliksen, L L

    1999-01-01

    Charles Dickens' novels are a source of vivid neurological descriptions. Besides Pickwickian syndrome, many other neurological descriptions can be found in Dickens' novels. David Copperfield contains several characters with movement disorders including generalized dystonia (Mr. Uriah Heep), restless legs syndrome (the waiter), cervical dystonia (Mr. Sharp) and spasmodic dysphonia (Mr. Creakle). These neurological descriptions an probably based on the observation of actual patients. PMID:10570623

  15. Climate changes associated with nuclear war

    NASA Technical Reports Server (NTRS)

    Toon, O. B.

    1986-01-01

    Nuclear war, featuring explosion of half the world arsenal of nuclear weapons, would cause urban and forest fires that would inject 20-650 megatons of smoke into the atmosphere. The Northern Hemisphere optical depth would increase to between 0.5-14. All models indicate an increase in optical depths, a large net radiation gain in the smoke layer, and an antigreenhouse effect at the surface. Significant global cooling would proceed, transforming the global climate to a large degree toward that of an airless world. Persisting deficiencies in the models are identified, noting research areas which would improve the accuracies of the predictions.

  16. The "O" Word: Issues in Outsourcing. Professional Associations React to the Challenge. Interviews with SLA's David Bender and AIIP's Jane Miller.

    ERIC Educational Resources Information Center

    Quint, Barbara

    1996-01-01

    The executive director of the Special Libraries Association (SLA) and the president of the Association of Independent Information Professionals (AIIP) answer questions about outsourcing information services. Relevant policy, vendor-client relationships, managerial considerations, and effects on libraries are discussed. Two sidebars offer 19…

  17. Battling Creaticide: An Interview with David C. Berliner

    ERIC Educational Resources Information Center

    Ambrose, Don

    2012-01-01

    This article presents an interview with David C. Berliner, a Regents' Professor in the College of Education at Arizona State University. His books include "Educational Psychology," "The Manufactured Crisis," and "The Handbook of Educational Psychology." He has served as president of the American Educational Research Association and of the…

  18. Distributed Access View Integrated Database (DAVID) system

    NASA Technical Reports Server (NTRS)

    Jacobs, Barry E.

    1991-01-01

    The Distributed Access View Integrated Database (DAVID) System, which was adopted by the Astrophysics Division for their Astrophysics Data System, is a solution to the system heterogeneity problem. The heterogeneous components of the Astrophysics problem is outlined. The Library and Library Consortium levels of the DAVID approach are described. The 'books' and 'kits' level is discussed. The Universal Object Typer Management System level is described. The relation of the DAVID project with the Small Business Innovative Research (SBIR) program is explained.

  19. Emergence of the nuclear industry and associated crime. Master's thesis

    SciTech Connect

    Vaught, J.W.

    1991-08-01

    Nuclear energy, in weapons production and electrical power generation, is a technology that has endured public scrutiny since the late 1940s. Societal acceptance of this industry has been affected by controversy in the following areas: health effects of exposure to radiation, possible consequences resulting from accidents, and nuclear nonproliferation. The literature review begins in Chapter 2 by examining the changing public perceptions of nuclear energy over the last forty years. Support for the ideals and practices of the industry has often wavered, due to media representation of incidents, accidents, and potential catastrophic events. The second part of the chapter highlights the crimes associated with nuclear energy in a chronological order of concern by nuclear industry security specialists. Research has found certain types of crime to be more prevalent during particular eras than others. Crimes instigated by spies, peace activists, terrorists, and the insider (employee) are reviewed, with an emphasis on insider crime.

  20. INTRODUCTION: David Sherrington as a mentor of young scientists

    NASA Astrophysics Data System (ADS)

    Goldbart, Paul M.

    2008-08-01

    the ones first developed in the setting of the Sherrington--Kirkpatrick model of spin glasses. What this small anecdote hints at is the vastness of the terrain over which research on spin glasses is having a deep and lasting impact. As scientists we are, I think it's fair to say, at least partially motivated by a desire to receive some recognition for our work, some evidence that it has been engaging and stimulating to others in the field. But David's work far transcends this model, being pivotal not only to researchers in the originally-intended domain of rather obscure magnetic alloys, but also far, far beyond: from neuroscience and biological information processing, to the social sciences, including economics, and on to probability theory, computer science, the next generation of optimization algorithms, and the entire field of complexity theory. Indeed, one can regard spin glasses in the guise of the Sherrington-Kirkpatrick model as a conceptual version of the silicon revolution: a curiosity-driven scientific endeavour that continues to catalyse utterly unanticipated progress over far-flung domains. David captured it all perfectly in the title of his 2001 Bakerian Lecture: 'Magnets, microchips, memories and markets: [the] statistical physics of complex systems.' Many of us would consider ourselves wonderfully fortunate if our work were to have just a small fraction of the impact that David's has. Moreover, the scientific panorama revealed by investigations stimulated by David's work is beautiful, shocking and inspiring, a panorama broader still than condensed matter theory or even physics itself. So, when our spirits are down and our brows furrowed by some painful integral or a bug in our computer code, let us remember to pause and revel in the astonishing confluence of scientific themes that the Sherrington-Kirkpatrick model and its associates capture. To echo a view I first heard from Giorgio Parisi: I'm not sure if there is anything more rich or surprising in

  1. A Star of David catenane

    NASA Astrophysics Data System (ADS)

    Leigh, David A.; Pritchard, Robin G.; Stephens, Alexander J.

    2014-11-01

    We describe the synthesis of a [2]catenane that consists of two triply entwined 114-membered rings, a molecular link. The woven scaffold is a hexameric circular helicate generated by the assembly of six tris(bipyridine) ligands with six iron(II) cations, with the size of the helicate promoted by the use of sulfate counterions. The structure of the ligand extension directs subsequent covalent capture of the catenane by ring-closing olefin metathesis. Confirmation of the Star of David topology (two rings, six crossings) is provided by NMR spectroscopy, mass spectrometry and X-ray crystallography. Extraction of the iron(II) ions with tetrasodium ethylenediaminetetraacetate affords the wholly organic molecular link. The self-assembly of interwoven circular frameworks of controlled size, and their subsequent closure by multiple directed covalent bond-forming reactions, provides a powerful strategy for the synthesis of molecular topologies of ever-increasing complexity.

  2. David Mechanic: Professional Zombie Hunter.

    PubMed

    Hafferty, Frederic W; Tilburt, Jon

    2016-08-01

    Within the fields of medicine and sociology, the descriptor "profession" (along with its brethren: profession, professionalization, and professionalism) has had a rich etymological history, with terms taking on different meanings at different times-sometimes trespassing into shibboleth and jargon. This etymological journey has co-evolved with the career of David Mechanic to whom this issue of the Journal of Health Politics, Policy and Law is devoted. We exploit a provocative metaphor applied to Mechanic's work on the challenges facing medicine as a profession as a playful exegesis on what we call "profession" to excavate an ensconced and encrusted domain of health jargon operating at the tensive interface of society and modern medical work.

  3. David Mechanic: Professional Zombie Hunter.

    PubMed

    Hafferty, Frederic W; Tilburt, Jon

    2016-08-01

    Within the fields of medicine and sociology, the descriptor "profession" (along with its brethren: profession, professionalization, and professionalism) has had a rich etymological history, with terms taking on different meanings at different times-sometimes trespassing into shibboleth and jargon. This etymological journey has co-evolved with the career of David Mechanic to whom this issue of the Journal of Health Politics, Policy and Law is devoted. We exploit a provocative metaphor applied to Mechanic's work on the challenges facing medicine as a profession as a playful exegesis on what we call "profession" to excavate an ensconced and encrusted domain of health jargon operating at the tensive interface of society and modern medical work. PMID:27127250

  4. David Hubel and Torsten Wiesel.

    PubMed

    Hubel, David; Wiesel, Torsten

    2012-07-26

    While attending medical school at McGill, David Hubel developed an interest in the nervous system during the summers he spent at the Montreal Neurological Institute. After heading to the United States in 1954 for a Neurology year at Johns Hopkins, he was drafted by the army and was assigned to the Neuropsychiatry Division at the Walter Reed Hospital, where he began his career in research and did his first recordings from the visual cortex of sleeping and awake cats. In 1958, he moved to the lab of Stephen Kuffler at Johns Hopkins, where he began a long and fruitful collaboration with Torsten Wiesel. Born in Sweden, Torsten Wiesel began his scientific career at the Karolinska Institute, where he received his medical degree in 1954. After spending a year in Carl Gustaf Bernhard's laboratory doing basic neurophysiological research, he moved to the United States to be a postdoctoral fellow with Stephen Kuffler. It was at Johns Hopkins where he met David Hubel in 1958, and they began working together on exploring the receptive field properties of neurons in the visual cortex. Their collaboration continued until the late seventies. Hubel and Wiesel's work provided fundamental insight into information processing in the visual system and laid the foundation for the field of visual neuroscience. They have had many achievements, including--but not limited to--the discovery of orientation selectivity in visual cortex neurons and the characterization of the columnar organization of visual cortex through their discovery of orientation columns and ocular-dominance columns. Their work earned them the Nobel Prize for Physiology or Medicine in 1981, which they shared with Roger Sperry. PMID:22841302

  5. David Hubel and Torsten Wiesel.

    PubMed

    Hubel, David; Wiesel, Torsten

    2012-07-26

    While attending medical school at McGill, David Hubel developed an interest in the nervous system during the summers he spent at the Montreal Neurological Institute. After heading to the United States in 1954 for a Neurology year at Johns Hopkins, he was drafted by the army and was assigned to the Neuropsychiatry Division at the Walter Reed Hospital, where he began his career in research and did his first recordings from the visual cortex of sleeping and awake cats. In 1958, he moved to the lab of Stephen Kuffler at Johns Hopkins, where he began a long and fruitful collaboration with Torsten Wiesel. Born in Sweden, Torsten Wiesel began his scientific career at the Karolinska Institute, where he received his medical degree in 1954. After spending a year in Carl Gustaf Bernhard's laboratory doing basic neurophysiological research, he moved to the United States to be a postdoctoral fellow with Stephen Kuffler. It was at Johns Hopkins where he met David Hubel in 1958, and they began working together on exploring the receptive field properties of neurons in the visual cortex. Their collaboration continued until the late seventies. Hubel and Wiesel's work provided fundamental insight into information processing in the visual system and laid the foundation for the field of visual neuroscience. They have had many achievements, including--but not limited to--the discovery of orientation selectivity in visual cortex neurons and the characterization of the columnar organization of visual cortex through their discovery of orientation columns and ocular-dominance columns. Their work earned them the Nobel Prize for Physiology or Medicine in 1981, which they shared with Roger Sperry.

  6. David L. Harrison: A Work Of Art

    ERIC Educational Resources Information Center

    Raymond, Allen

    2005-01-01

    This article describes poet and writer David L. Harrison. A former School Board Chairman from Springfield, MO, David was responsible for beginning an annual "Teacher Appreciation Banquet" and for launching the "Sky High for Reading" program. The "Sky High for Reading" program encourages children in Springfield to read enough books so that, if…

  7. Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions

    PubMed Central

    Wang, Jayson; Shiels, Carol; Sasieni, Peter; Wu, Pei Jun; Islam, Suhail A.; Freemont, Paul S.; Sheer, Denise

    2004-01-01

    The promyelocytic leukemia (PML) protein is aggregated into nuclear bodies that are associated with diverse nuclear processes. Here, we report that the distance between a locus and its nearest PML body correlates with the transcriptional activity and gene density around the locus. Genes on the active X chromosome are more significantly associated with PML bodies than their silenced homologues on the inactive X chromosome. We also found that a histone-encoding gene cluster, which is transcribed only in S-phase, is more strongly associated with PML bodies in S-phase than in G0/G1 phase of the cell cycle. However, visualization of specific RNA transcripts for several genes showed that PML bodies were not themselves sites of transcription for these genes. Furthermore, knock-down of PML bodies by RNA interference did not preferentially change the expression of genes closely associated with PML bodies. We propose that PML bodies form in nuclear compartments of high transcriptional activity, but they do not directly regulate transcription of genes in these compartments. PMID:14970191

  8. Detection of special nuclear materials with the associate particle technique

    SciTech Connect

    Carasco, Cedric; Deyglun, Clement; Perot, Bertrand; Eleon, Cyrille; Normand, Stephane; Sannie, Guillaume; Boudergui, Karim; Corre, Gwenole; Konzdrasovs, Vladimir; Pras, Philippe

    2013-04-19

    In the frame of the French trans-governmental R and D program against chemical, biological, radiological, nuclear and explosives (CBRN-E) threats, CEA is studying the detection of Special Nuclear Materials (SNM) by neutron interrogation with fast neutrons produced by an associated particle sealed tube neutron generator. The deuterium-tritium fusion reaction produces an alpha particle and a 14 MeV neutron almost back to back, allowing tagging neutron emission both in time and direction with an alpha particle position-sensitive sensor embedded in the generator. Fission prompt neutrons and gamma rays induced by tagged neutrons which are tagged by an alpha particle are detected in coincidence with plastic scintillators. This paper presents numerical simulations performed with the MCNP-PoliMi Monte Carlo computer code and with post processing software developed with the ROOT data analysis package. False coincidences due to neutron and photon scattering between adjacent detectors (cross talk) are filtered out to increase the selectivity between nuclear and benign materials. Accidental coincidences, which are not correlated to an alpha particle, are also taken into account in the numerical model, as well as counting statistics, and the time-energy resolution of the data acquisition system. Such realistic calculations show that relevant quantities of SNM (few kg) can be distinguished from cargo and shielding materials in 10 min acquisitions. First laboratory tests of the system under development in CEA laboratories are also presented.

  9. Exploring the Living Planet with David Attenborough.

    ERIC Educational Resources Information Center

    Burgess, Jacquelin; Unwin, David

    1984-01-01

    In this interview David Attenborough, the celebrated natural history film maker and writer, talks about his highly successful television series, "The Living Planet." Devoted to the exposition of the world's ecosystems, the film represents a significant example of popular geographic education. (RM)

  10. Reading Pictures: An Interview with David Wiesner

    ERIC Educational Resources Information Center

    Varga-Dobai, Kinga

    2008-01-01

    Two-time Caldecott Honor winner (Free Fall, Sector 7) and three-time Caldecott Medal winner (Tuesday, The Three Pigs, Flotsam), David Wiesner is regarded as one of the most remarkable creators of visual storytelling living today. Wiesner is well known for his innovative and unique subject matter and his sophisticated painting-like illustrations…

  11. Interview with Dr. David H. Kalsbeek

    ERIC Educational Resources Information Center

    Sauter, David M.

    2005-01-01

    David H. Kalsbeek currently is vice president for enrollment management at DePaul University in Chicago, Illinois. In that capacity, he leads the marketing and enrollment development strategies for the nation's largest and fastest-growing Catholic university, enrolling 23,000 students in eight colleges and six campuses throughout the greater…

  12. Another Perspective: An Interview with David Smith

    ERIC Educational Resources Information Center

    Bowman, Ruth A.; Johnson, Kelli

    2005-01-01

    To provide another perspective on evaluation within nonformal settings, "New Directions for Evaluation" recently interviewed David Smith, the coordinator of the Professional Learning to Close the Achievement Gap program for the Kansas City, Kansas, Public Schools, who has extensive background in education and educational research. He formerly held…

  13. A Conversation with...David Satcher.

    ERIC Educational Resources Information Center

    Campbell, Neil A.

    1996-01-01

    David Satcher began his career as a medical geneticist and was appointed director of the Centers for Disease Control and Prevention (CDC) in 1993. In this interview, Dr. Satcher talks about the responsibilities of the CDC and explains how a childhood experience inspired his interest in medicine and his continuing commitment to community service.…

  14. David L. Gutmann (1925-2013).

    PubMed

    Rose, Jon; Huyck, Margaret; Grunes, Jerome

    2014-01-01

    David L. Gutmann, a pioneer in geropsychology and professor emeritus at Northwestern University, died on November 3, 2013, at the age of 88. A student of Bernice Neugarten, Bruno Bettelheim, and Erik Erikson, Gutmann discovered changes in adult psychological development related to parenting styles that held across diverse cultures.

  15. David L. Gutmann (1925-2013).

    PubMed

    Rose, Jon; Huyck, Margaret; Grunes, Jerome

    2014-01-01

    David L. Gutmann, a pioneer in geropsychology and professor emeritus at Northwestern University, died on November 3, 2013, at the age of 88. A student of Bernice Neugarten, Bruno Bettelheim, and Erik Erikson, Gutmann discovered changes in adult psychological development related to parenting styles that held across diverse cultures. PMID:25046720

  16. Family Matters: A Conversation with David Popenoe

    ERIC Educational Resources Information Center

    Iannone, Carol

    2009-01-01

    This article presents an interview with Professor David Popenoe, author of the controversial book "Disturbing the Nest: Family Change and Decline in Modern Societies" (1988). Popenoe heads the National Marriage Project at Rutgers University, where he taught sociology for forty-five years until his recent retirement. Here, Popenoe discusses his…

  17. Speaking Personally--With David Foster

    ERIC Educational Resources Information Center

    American Journal of Distance Education, 2010

    2010-01-01

    David Foster is the founder of Kryterion, an Internet test administration company, and currently serves there as chief scientist and executive vice president. He is the author of numerous articles for industry trade journals and textbooks and sits on the Council for the International Test Commission. In this interview, Foster talks about his…

  18. David Ben-Gurion: A Creative Leader

    ERIC Educational Resources Information Center

    Rosemarin, Shoshana

    2014-01-01

    David Ben-Gurion (1886-1973), the first Prime Minister of Israel, is included in Pasternak's (2001) list of the nine most memorable leaders of the twentieth century. All of them are remembered for the reforms they initiated. Roosevelt (USA), Stalin (Russia), Castro (Cuba), and Thatcher (England) focused on social-economical changes, whereas…

  19. 76 FR 12971 - David E. Berman: Debarment Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-09

    ... HUMAN SERVICES Food and Drug Administration David E. Berman: Debarment Order AGENCY: Food and Drug... the Federal Food, Drug, and Cosmetic Act (the FD&C Act) debarring David E. Berman, MD, for 3 years... 1410.35), finds that David E. Berman has been convicted of a misdemeanor under Federal law for...

  20. Interface between astrophysical datasets and distributed database management systems (DAVID)

    NASA Technical Reports Server (NTRS)

    Iyengar, S. S.

    1988-01-01

    This is a status report on the progress of the DAVID (Distributed Access View Integrated Database Management System) project being carried out at Louisiana State University, Baton Rouge, Louisiana. The objective is to implement an interface between Astrophysical datasets and DAVID. Discussed are design details and implementation specifics between DAVID and astrophysical datasets.

  1. 77 FR 26765 - David H.M. Phelps: Debarment Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... HUMAN SERVICES Food and Drug Administration David H.M. Phelps: Debarment Order AGENCY: Food and Drug... under the Federal Food, Drug, and Cosmetic Act (FD&C Act) debarring David H.M. Phelps for a period of 20... Manual Guide 1410.35), finds that Mr. David H.M. Phelps has been convicted of 10 felony counts...

  2. Nuclear attitudes and reactions: associations with depression, drug use, and quality of life

    SciTech Connect

    Newcomb, M.D.

    1986-05-01

    For 40 years the world has lived with the threat of nuclear war and, recently, with the possibility of nuclear power plant accidents. Although virtually every generation must confront various national or international crises, the threat of nuclear war is unprecedented in its destructive potential. This study is an attempt to assess attitudes and amount of distress associated with the ever-present threat of nuclear war and the possibility of accidents at nuclear power plants. The Nuclear Attitudes Questionnaire (NAQ) consists of 15 items and was administered to 722 young adults who have grown up in the nuclear age. The items were found to reflect four latent factors of nuclear concern, nuclear support, fear of the future, and nuclear denial, all of which in turn represent a second-order construct of nuclear anxiety. Women reported significantly more nuclear concern, less nuclear support, more fear of the future, and less nuclear denial than did men. In latent-variable models, nuclear anxiety was found to be significantly associated with less purpose in life, less life satisfaction, more powerlessness, more depression, and more drug use. It is concluded that the threat of nuclear war and accidents is significantly related to psychological distress and may disturb normal maturational development.

  3. David Alan Walker (1928-2012).

    PubMed

    Edwards, Gerald E; Heber, Ulrich

    2012-06-01

    David Alan Walker, Emeritus Professor of Biology, University of Sheffield, UK and Fellow of the Royal Society, died on February 13, 2012. David had a marvelous 60 year career as a scientist, during which he was a researcher, mentor, valued colleague, and a prolific writer in the field of photosynthesis. His career was marked by creative breakthroughs in isolation and analysis of chloroplast metabolism in vitro and simple but valuable technical advances for measurement of photosynthesis in vivo that remain relevant on a global scale to production of crops and biofuels, as well as plant responses to climate change. We include here personal remembrances by the authors (GEE and UH), and by (in alphabetical order): Zoran Cerovic (France), Bob Furbank (Australia), Geoffrey Hind (USA), John Humby (UK), Agu Laisk (Estonia), Peter Lea (UK), Ross Lilley (Australia), Barry Osmond (Australia), Simon Robinson (Australia) and Charles Stirling (UK). PMID:22638915

  4. The conserved domain CR2 of Epstein-Barr virus nuclear antigen leader protein is responsible not only for nuclear matrix association but also for nuclear localization.

    PubMed

    Yokoyama, A; Kawaguchi, Y; Kitabayashi, I; Ohki, M; Hirai, K

    2001-01-20

    There is a growing body of evidence for the importance of the nuclear matrix in various nuclear events including gene expression and DNA replication. Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a nuclear matrix-associated protein that has been suggested to play an important role in EBV-induced transformation. To define the biological significance of the association of EBNA-LP with the nuclear matrix, we mapped the domain of EBNA-LP responsible for nuclear matrix association and investigated the functions of the EBNA-LP mutant mutagenized by substitution of alanines for the cluster of arginine residues in the mapped region. The results of the present study were as follows. (i) Transiently expressed EBNA-LP in COS-7 or BOSC23 cells was associated with the nuclear matrix, similarly to that in EBV-infected B cells. (ii) Mutational analysis of EBNA-LP revealed that a 10-amino acid segment of EBNA-LP is critical for nuclear matrix association of the protein. Interestingly, the identified region overlapped with the region CR2 of EBNA-LP conserved among a subset of primate gammaherpesviruses. The identified segment is referred to as EBNA-LP NMTS (nuclear matrix targeting signal). (iii) The EBNA-LP mutant with the arginine to alanine substitutions in NMTS was no longer localized not only to the nuclear matrix but also to the nucleus. (iv) The EBNA-LP mutant lacked its ability to coactivate EBNA-2-dependent transactivation. These results indicated that EBNA-LP needs to be localized in the nucleus and/or associated with the nuclear matrix through CR2 to elicit its function such as the coactivation of the EBNA-2-dependent transcriptional activation. PMID:11162796

  5. Nuclear cardiology core syllabus of the European Association of Cardiovascular Imaging (EACVI).

    PubMed

    Gimelli, Alessia; Neglia, Danilo; Schindler, Thomas H; Cosyns, Bernard; Lancellotti, Patrizio; Kitsiou, Anastasia

    2015-04-01

    The European Association of Cardiovascular Imaging (EACVI) Core Syllabus for Nuclear Cardiology is now available online. The syllabus lists key elements of knowledge in nuclear cardiology. It represents a framework for the development of training curricula and provides expected knowledge-based learning outcomes to the nuclear cardiology trainees.

  6. Structural Seismic Risk at David City, Panama

    NASA Astrophysics Data System (ADS)

    Camacho, E.; Battlo, J.; Novelo-Casanova, D. A.; Tapia, A.; Lindhom, C.

    2007-12-01

    At the southwest margin of the Isthmus of Panama, the Cocos, Nazca and Panama Microplate join in a triple junction. In this tectonic setting, the Panama Fracture Zone (PFZ) which bounds the Nazca and Cocos plate, subducts in an oblique and shallow manner. This zone is one of the most active seismic areas of Central America. On July 18, 1934, the largest earthquake in Panama in historical times (Ms= 7.7) occurred in its northern region. This event caused extensive damage to towns located in the border of Panama and Costa Rica and during the two subsequent days, six aftershocks with magnitude greater than 6.0 were recorded. David City, with 130,000 inhabitants is the most important urban center in southwestern Panama and lies at the northern end of the PFZ. This city was impacted by the strong destructive earthquakes (Ms>7.0) that took place in 1879 and 1934, both with epicenters located on the northern terminus of the PFZ. In this work, we collected and digitized historical seismograms to measure the centroid moment tensor (CMT) from the main 1934 earthquake. Additionally, we gathered new macroseismic information to create improved and more complete isoseismals maps of the 1879 and 1934 events. We determined the probabilistic seismic hazard for David City using records of historical and recent seismicity and the characteristics of local faults. The hazard computation results are presented as peak iso-acceleration curves for rock/hard soil for a recurrence time of 500 years. An elastic response spectrum was obtained with a uniform exceedance probability of 10% in 50 years with one degree of freedom and 5% of damping. Our results indicate maximum peak ground acceleration (PGA) in downtown David of 3.8 and 4.5 m/s2 with a probability annual exceedance of 0.002 and 0.001, respectively. Structural vulnerability was determined analyzing the quality and construction design of housing, buildings, and critical facilities as well as the type of soil where these structures

  7. Mitochondrial regulation of cancer associated nuclear DNA methylation

    SciTech Connect

    Xie Chenghui; Naito, Akihiro; Mizumachi, Takatsugu; Evans, Teresa T.; Douglas, Michael G.; Cooney, Craig A.; Fan Chunyang; Higuchi, Masahiro

    2007-12-21

    The onset and progression of cancer is associated with the methylation-dependent silencing of specific genes, however, the mechanism and its regulation have not been established. We previously demonstrated that reduction of mitochondrial DNA content induces cancer progression. Here we found that mitochondrial DNA-deficient LN{rho}0-8 activates the hypermethylation of the nuclear DNA promoters including the promoter CpG islands of the endothelin B receptor, O{sup 6}-methylguanine-DNA methyltransferase, and E-cadherin. These are unmethylated and the corresponding gene products are expressed in the parental LNCaP containing mitochondrial DNA. The absence of mitochondrial DNA induced DNA methyltransferase 1 expression which was responsible for the methylation patterns observed. Inhibition of DNA methyltransferase eliminated hypermethylation and expressed gene products in LN{rho}0-8. These studies demonstrate loss or reduction of mitochondrial DNA resulted in the induction of DNA methyltransferase 1, hypermethylation of the promoters of endothelin B receptor, O{sup 6}-methylguanine-DNA methyltransferase, and E-cadherin, and reduction of the corresponding gene products.

  8. First Scholarship at AGU Established by David E. Lumley

    NASA Astrophysics Data System (ADS)

    Tahar, Joanna G.

    2009-09-01

    Shortly after AGU launched its annual voluntary contribution campaign last year—the theme was “Building Tomorrow's Talent Today”—the Union's development office received an e-mail message from David E. Lumley about establishing a scholarship for a high-school student or undergraduate. Many scientific societies and associations have quite a few named scholarships, but for AGU this was a new concept. Lumley was sure of what he wanted to do and even more excited when he learned that his scholarship would be a first for AGU. “I want to help inspire today's young minds to work on problems of global importance in both the energy and environment sectors of industry and academia,” Lumley said. Recipients of the David E. Lumley Young Scientist Scholarship for Energy and Environmental Science will be expected to present a paper and to participate in various student activities at Fall Meeting. “Meeting some of the ‘giants’ of geoscience and getting their feedback on research is a big deal for these young students. We sometimes lose sight of this,” he said.

  9. Instrument and spacecraft faults associated with nuclear radiation in space

    NASA Technical Reports Server (NTRS)

    Trainos, J. H.

    1994-01-01

    A review is given which surveys the variety of faults and failures which have occurred in space due both to the effects of single, energetic nuclear particles, as well as effects due to the accumulated ionizing dose or the fluence of nuclear particles. The review covers a variety of problems with sensors, electronics, instruments and spacecraft from several countries.

  10. Constructibility issues associated with a nuclear waste repository in basalt

    SciTech Connect

    Turner, D.A.

    1981-12-04

    This report contains the text and slide reproductions of a speech on nuclear waste disposal in basalt. The presentation addresses the layout of repository access shafts and subsurface facilities resulting from the conceptual design of a nuclear repository in basalt. The constructibility issues that must be resolved prior to construction are described. (DMC)

  11. Discussion of David Thissen's Bad Questions: An Essay Involving Item Response Theory

    ERIC Educational Resources Information Center

    Ackerman, Terry

    2016-01-01

    In this commentary, University of North Carolina's associate dean of research and assessment at the School of Education Terry Ackerman poses questions and shares his thoughts on David Thissen's essay, "Bad Questions: An Essay Involving Item Response Theory" (this issue). Ackerman begins by considering the two purposes of Item Response…

  12. America's foremost early astronomer. [David Rittenhouse

    NASA Technical Reports Server (NTRS)

    Rubincam, David Parry; Rubincam, Milton, II

    1995-01-01

    The life of 18th century astronomer, craftsman, and partriot David Rittenhouse is detailed. As a craftsman, he distinguished himself as one of the foremost builders of clocks. He also built magnetic compasses and surveying instruments. The finest examples of his craftsmanship are considered two orreries, mechanical solar systems. In terms of astronomical observations, his best-known contribution was his observation of the transit of Venus in 1769. Rittenhouse constructed the first diffraction grating. Working as Treasurer of Pennsylvania throughout the Revolution, he became the first director of the Mint in 1792. Astronomical observations in later life included charting the position of Uranus after its discovery.

  13. Obituary: David Q. Wark, 1918-2002

    NASA Astrophysics Data System (ADS)

    McMillin, Larry Max

    2003-12-01

    the American Meteorological Society, the Lloyd V. Berkner Space Utilization Award from the American Astronautical Society, and the Robert M. Losey Award, from the American Institute of Aeronautics and Astronautics. David Quentin Wark was born on 25 March 1918, in Spokane, Washington. He was the fourth and last child of Percival Damon Wark and Clara Belle (née Mackey) Wark. In 1921 his family moved to Altadena and Pasadena, California, where he lived until 1939. He attended Altadena Elementary School, Edison Elementary School, Washington Junior High School, Pasadena High School, and Pasadena Junior College. From 1938 to 1939, and again in the summer of 1940, he worked for the Associated Press and David Lawrence to earn money to resume his education. In 1939, he entered the University of California, Berkeley, from which he graduated with a BA in Astronomy with honors in May 1941. From 1941 to 1942 he did graduate study in meteorology at the University of California, Los Angeles. He resumed graduate studies part time in 1948 at the University of California, Berkeley, while working full time at the U.S. Weather Bureau and graduated with a PhD in Astronomy in January 1959. He remembered those times as tough days driving back and forth to Berkeley and living in Half-Moon Bay. Dr. Wark's professional career began in 1942 at the U.S. Naval Observatory, where he served as a Naval Officer until 1946. He then went to work for the U.S. Weather Bureau. He spent the first three years of that period in Istres, France, Frankfurt and Munich, Germany, and Cairo Egypt. From 1949 through 1958 he served at the Aviation Weather Forecast Office in San Francisco. He then moved to the U.S. Weather Bureau Office in Suitland, Maryland, where he worked from November 1958 until 3 July 1999, when he officially retired. He actually retired from NOAA because during this time, he saw the U.S. Weather Bureau become part of ESSA which, in turn, became a part the National Oceanic and Atmospheric

  14. 3. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    3. Historic American Buildings Survey, David Aronow, Photographer circa 1924, DETAIL OF FRONT ELEVATION SHOWING PROJECTING VERANDA. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  15. 2. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    2. Historic American Buildings Survey, David Aronow, Photographer circa 1924, FRONT ELEVATION SHOWING BELLTOWER AND PROJECTING VERANDA. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  16. Several Novel Nuclear Envelope Transmembrane Proteins Identified in Skeletal Muscle Have Cytoskeletal Associations*

    PubMed Central

    Wilkie, Gavin S.; Korfali, Nadia; Swanson, Selene K.; Malik, Poonam; Srsen, Vlastimil; Batrakou, Dzmitry G.; de las Heras, Jose; Zuleger, Nikolaj; Kerr, Alastair R. W.; Florens, Laurence; Schirmer, Eric C.

    2011-01-01

    Nuclear envelopes from liver and a neuroblastoma cell line have previously been analyzed by proteomics; however, most diseases associated with the nuclear envelope affect muscle. To determine whether muscle has unique nuclear envelope proteins, rat skeletal muscle nuclear envelopes were prepared and analyzed by multidimensional protein identification technology. Many novel muscle-specific proteins were identified that did not appear in previous nuclear envelope data sets. Nuclear envelope residence was confirmed for 11 of these by expression of fusion proteins and by antibody staining of muscle tissue cryosections. Moreover, transcript levels for several of the newly identified nuclear envelope transmembrane proteins increased during muscle differentiation using mouse and human in vitro model systems. Some of these proteins tracked with microtubules at the nuclear surface in interphase cells and accumulated at the base of the microtubule spindle in mitotic cells, suggesting they may associate with complexes that connect the nucleus to the cytoskeleton. The finding of tissue-specific proteins in the skeletal muscle nuclear envelope proteome argues the importance of analyzing nuclear envelopes from all tissues linked to disease and suggests that general investigation of tissue differences in organellar proteomes might yield critical insights. PMID:20876400

  17. Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations.

    PubMed

    Wilkie, Gavin S; Korfali, Nadia; Swanson, Selene K; Malik, Poonam; Srsen, Vlastimil; Batrakou, Dzmitry G; de las Heras, Jose; Zuleger, Nikolaj; Kerr, Alastair R W; Florens, Laurence; Schirmer, Eric C

    2011-01-01

    Nuclear envelopes from liver and a neuroblastoma cell line have previously been analyzed by proteomics; however, most diseases associated with the nuclear envelope affect muscle. To determine whether muscle has unique nuclear envelope proteins, rat skeletal muscle nuclear envelopes were prepared and analyzed by multidimensional protein identification technology. Many novel muscle-specific proteins were identified that did not appear in previous nuclear envelope data sets. Nuclear envelope residence was confirmed for 11 of these by expression of fusion proteins and by antibody staining of muscle tissue cryosections. Moreover, transcript levels for several of the newly identified nuclear envelope transmembrane proteins increased during muscle differentiation using mouse and human in vitro model systems. Some of these proteins tracked with microtubules at the nuclear surface in interphase cells and accumulated at the base of the microtubule spindle in mitotic cells, suggesting they may associate with complexes that connect the nucleus to the cytoskeleton. The finding of tissue-specific proteins in the skeletal muscle nuclear envelope proteome argues the importance of analyzing nuclear envelopes from all tissues linked to disease and suggests that general investigation of tissue differences in organellar proteomes might yield critical insights. PMID:20876400

  18. David Lasser: An American Spaceflight Pioneer

    NASA Astrophysics Data System (ADS)

    Ciancone, Michael L.; Lasser, Amelia

    2002-01-01

    David Lasser was one of the founders of the American Interplanetary Society (later known as the American Rocket Society) and author of the first English-language book (in 1931) on the prospects of human spaceflight. Yet his involvement in the fledgling spaceflight movement was short-lived as he soon moved on to pursue a distinguished career in the cause of workers rights. In lieu of an oral history, the author corresponded with Mr. Lasser on a regular basis in the years before his death in 1996 to gather Mr. Lasser's views on human spaceflight activities as viewed from his unique perspective. This paper will document that correspondence with one of America's original spaceflight pioneers.

  19. David D. Derse, 1949-2009

    PubMed Central

    2009-01-01

    David D. Derse, Ph.D., Head of the Retrovirus Gene Expression Section in the HIV Drug Resistance Program at the National Cancer Institute-Frederick (NCI-Frederick), passed away on October 9, 2009, a scant six weeks after being diagnosed with liver cancer. It was with great sadness that family, friends, and colleagues gathered together for his memorial service on Saturday, October 17, 2009, at the Middletown United Methodist Church in Maryland. As a NCI scientist since 1986, Dave studied the molecular mechanisms of infection and replication of a number of different types of retroviruses. Dave became an internationally known expert on human T cell lymphotrophic viruses type 1 and 2 (HTLV-1 and HTLV-2) and served on the editorial boards of Virology and Retrovirology. His most recent studies focused on the mechanisms of HTLV-1 virion morphogenesis, transmission, and replication. PMID:19951436

  20. David Lasser - An American Spaceflight Pioneer

    NASA Technical Reports Server (NTRS)

    Ciancone, Michael L.; Lasser, Amelia

    2002-01-01

    David Lasser was one of the founders of the American Interplanetary Society (later known as the American Rocket Society) and author of the first English-language book (in 1931) on the use of rockets for human spaceflight. His involvement in the fledgling spaceflight movement was short-lived as he moved on to pursue a distinguished, if turbulent, career in the labor movement. In lieu of an oral history, Mr. Lasser provided his recollections on the pioneering days of rocketry and his thoughts on mankind's destiny in space. This paper provides an overview of Mr. Lasser's life and accomplishments as an American spaceflight visionary, along with a compilation of the information that he graciously provided.

  1. Rainforest pioneer. Millennium trailblazers 3: David Cassell.

    PubMed

    Gilmour, D

    1999-01-01

    The Iwokrama International Centre for Rain Forest Conservation in Guyana is headed by Australian forester David Cassells who is also chairman of the Advisory Group for the World Conservation Union Forest Conservation Program. He states that this program is different from other projects to conserve tropical forests since it focuses on financial sustainability and self-sufficiency. He also plans that the revenue for the center will come from a mixture of eco-forestry with certified logging, ecotourism, sustainable production of non-timber products such as vines and latexes, bioprospecting, and the sale of forest management expertise. He further added that the program's success could change the way people value and use tropical forests.

  2. David Lukens Reasoner (1941-1992)

    NASA Astrophysics Data System (ADS)

    Chappell, Rick

    David Lukens Reasoner, former head of NASA's Ionospheric Physics branch, died on April 21, 1992. Reasoner was born July 1, 1941. He worked tirelessly to expand NASA's Space Physics Division, bringing his deep experience and personal expertise to bear on the challenges of growth.During the magical period of the late 1950s and early 1960s when America turned its eyes toward space and the Moon, David Lukens Reasoner journeyed north from the nearby Texas town of Dickinson to Rice University with an idea of getting involved in exploring the frontiers of space. He pursued a course of study in electrical engineering and received a bachelor's degree in 1963 and a master's degree in 1964. In the early 1960s, the Space Science Department at Rice was formed, and President John Kennedy visited to say that America chose to go to space not because it is easy but because it is hard and because it would require the very best talents of our nation to succeed. Dave Reasoner was one of those talented people. His excellence in electrical engineering and physics, combined with his natural abilities in the laboratory, suited him ideally for building the machines of space. As a student, he built sounding rocket payloads and multiple instruments for satellites and experiment packages that were placed on the Moon by the Apollo astronauts. He completed his doctoral degree in space science in 1968. It was in these early thrilling days of space exploration that I first met Dave, beginning a friendship and collegial relationship that was to last 27 years.

  3. Silencing by nuclear matrix attachment distinguishes cell-type specificity: association with increased proliferation capacity

    PubMed Central

    Linnemann, Amelia K.; Krawetz, Stephen A.

    2009-01-01

    DNA loop organization by nuclear scaffold/matrix attachment is a key regulator of gene expression that may provide a means to modulate phenotype. We have previously shown that attachment of genes to the NaCl-isolated nuclear matrix correlates with their silencing in HeLa cells. In contrast, expressed genes were associated with the lithium 3,5-diiodosalicylate (LIS)-isolated nuclear scaffold. To define their role in determining phenotype matrix attached regions (MARs) on human chromosomes 14–18 were identified as a function of expression in a primary cell line. The locations of MARs in aortic adventitial fibroblast (AoAF) cells were very stable (r = 0.909) and 96% of genes attached at MARs are silent (P < 0.001). Approximately one-third of the genes uniquely expressed in AoAF cells were associated with the HeLa cell nuclear matrix and silenced. Comparatively, 81% were associated with the AoAF cell nuclear scaffold (P < 0.001) and expressed. This suggests that nuclear scaffold/matrix association mediates a portion of cell type-specific gene expression thereby modulating phenotype. Interestingly, nuclear matrix attachment and thus silencing of specific genes that regulate proliferation and maintain the integrity of the HeLa cell genome suggests that transformation may at least in part be achieved through aberrant nuclear matrix attachment. PMID:19276204

  4. 76 FR 7837 - Magill, David W.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Magill, David W.; Notice of Filing Take notice that on February 4, 2011, David W. Magill submitted for filing, an application for authority to hold interlocking...

  5. Music: Part of the Basics at David Douglas and Salem.

    ERIC Educational Resources Information Center

    Pheasant, Marilyn

    1985-01-01

    This bulletin highlights elements of the music programs in two Oregon school districts--David Douglas School District 40 and Salem School District 24J--that have kept these programs viable in spite of financial constraints. Ingredients for success of the overall music program at David Douglas are first described. Important elements include hiring…

  6. 77 FR 71189 - Falck, David P.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... Energy Regulatory Commission Falck, David P.; Notice of Filing Take notice that on November 23, 2012, David P. Falck submitted for filing, an application for authority to hold interlocking positions...-8659. Comment Date: 5:00 p.m. Eastern Time on December 14, 2012. Dated: November 23, 2012. Kimberly...

  7. Third Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Third Annual David Derse Memorial Lecture and Award presentation was held on Nov. 18 at NCI at Frederick to honor the outstanding research accomplishments of David Derse, Ph.D., and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career.

  8. Teaching Students about the Environment with Henry David Thoreau

    ERIC Educational Resources Information Center

    Curriculum Review, 2008

    2008-01-01

    "Walden: The Ballad of Thoreau" is a two-act four-character play about the final two days writer Henry David Thoreau spent in his cabin before leaving Walden Pond. Teachers can use this play to teach about preserving the earth to students. This article presents a brief synopsis of the play and a brief biography of Henry David Thoreau.

  9. 75 FR 10244 - Ellsworth, David C.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Ellsworth, David C.; Notice of Filing February 25, 2010. Take notice that on February 12, 2010, David C. Ellsworth filed an informational report for authority to hold...

  10. The David and Goliath principle: cultural, ideological, and attitudinal underpinnings of the normative protection of low-status groups from criticism.

    PubMed

    Jeffries, Carla H; Hornsey, Matthew J; Sutton, Robbie M; Douglas, Karen M; Bain, Paul G

    2012-08-01

    Two studies documented the "David and Goliath" rule--the tendency for people to perceive criticism of "David" groups (groups with low power and status) as less normatively permissible than criticism of "Goliath" groups (groups with high power and status). The authors confirmed the existence of the David and Goliath rule across Western and Chinese cultures (Study 1). However, the rule was endorsed more strongly in Western than in Chinese cultures, an effect mediated by cultural differences in power distance. Study 2 identified the psychological underpinnings of this rule in an Australian sample. Lower social dominance orientation (SDO) was associated with greater endorsement of the rule, an effect mediated through the differential attribution of stereotypes. Specifically, those low in SDO were more likely to attribute traits of warmth and incompetence to David versus Goliath groups, a pattern of stereotypes that was related to the protection of David groups from criticism.

  11. PIASy, a nuclear matrix–associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies

    PubMed Central

    Sachdev, Shrikesh; Bruhn, Laurakay; Sieber, Heidemarie; Pichler, Andrea; Melchior, Frauke; Grosschedl, Rudolf

    2001-01-01

    The Wnt-responsive transcription factor LEF1 can activate transcription in association with β-catenin and repress transcription in association with Groucho. In search of additional regulatory mechanisms of LEF1 function, we identified the protein inhibitor of activated STAT, PIASy, as a novel interaction partner of LEF1. Coexpression of PIASy with LEF1 results in potent repression of LEF1 activity and in covalent modification of LEF1 with SUMO. PIASy markedly stimulates the sumoylation of LEF1 and multiple other proteins in vivo and functions as a SUMO E3 ligase for LEF1 in a reconstituted system in vitro. Moreover, PIASy binds to nuclear matrix–associated DNA sequences and targets LEF1 to nuclear bodies, suggesting that PIASy-mediated subnuclear sequestration accounts for the repression of LEF1 activity. PMID:11731474

  12. Obituary: David L. Band (1957-2009)

    NASA Astrophysics Data System (ADS)

    Cominsky, Lynn

    2011-12-01

    David L. Band, of Potomac Maryland, died on March 16, 2009 succumbing to a long battle with spinal cord cancer. His death at the age of 52 came as a shock to his many friends and colleagues in the physics and astronomy community. Band showed an early interest and exceptional aptitude for physics, leading to his acceptance at the Massachusetts Institute of Technology as an undergraduate student in 1975. After graduating from MIT with an undergraduate degree in Physics, Band continued as a graduate student in Physics at Harvard University. His emerging interest in Astrophysics led him to the Astronomy Department at the Harvard Smithsonian Center for Astrophysics (CfA), where he did his dissertation work with Jonathan Grindlay. His dissertation (1985) entitled "Non-thermal Radiation Mechanisms and Processes in SS433 and Active Galactic Nuclei" was "pioneering work on the physics of jets arising from black holes and models for their emission, including self-absorption, which previewed much to come, and even David's own later work on Gamma-ray Bursts," according to Grindlay who remained a personal friend and colleague of Band's. Following graduate school, Band held postdoctoral positions at the Lawrence Livermore Laboratory, the University of California at Berkeley and the Center for Astronomy and Space Sciences at the University of California San Diego where he worked on the BATSE experiment that was part of the Compton Gamma Ray Observatory (CGRO), launched in 1991. BATSE had as its main objective the study of cosmic gamma-ray bursts (GRBs) and made significant advances in this area of research. Band became a world-renowned figure in the emerging field of GRB studies. He is best known for his widely-used analytic form of gamma-ray burst spectra known as the "Band Function." After the CGRO mission ended, Band moved to the Los Alamos National Laboratory where he worked mainly on classified research but continued to work on GRB energetics and spectra. When NASA planned

  13. Second Annual David Derse Memorial Lecture and Award | Poster

    Cancer.gov

    By Anne Arthur, Guest Writer The Second Annual David Derse Memorial Lecture and Award presentation was held on November 12, 2013, at the NCI at Frederick Conference Center to honor David Derse’s outstanding research accomplishments and to stimulate the exchange of innovative ideas that Derse was well known for promoting throughout his scientific career. The Annual David Derse Memorial Lecture and Award is sponsored by the HIV Drug Resistance Program, with support from Hye Kyung Chung-Derse, Ph.D., the National Cancer Institute (NCI), the Foundation for the National Institutes of Health (NIH), and colleagues and friends of Derse who contributed to the memorial fund in his honor.

  14. Triptolide Induced Transcriptional Arrest is Associated with Changes in Nuclear Sub-Structure

    PubMed Central

    Leuenroth, Stephanie J.; Crews, Craig M.

    2008-01-01

    Triptolide, an active component of the medicinal herb, lei gong teng, is a potent anti-cancer and anti-inflammatory therapeutic. It potently inhibits NFκB transcriptional activation subsequent to DNA binding, although a precise mechanism is as yet unknown. Here, we report that triptolide also induces distinct nuclear sub-structural changes in HeLa cells. These changes in the nucleolus and nuclear speckles are reversible and dependent on both time and concentration. Furthermore, nuclear changes occurred within hours of triptolide treatment and were calcium and caspase independent. Rounding of nuclear speckles, an indication of transcriptional arrest was evident and was associated with a decrease in RNA Polymerase II CTD Ser2 phosphorylation. Additionally, the nucleolus disassembled and RNA Pol I activity declined subsequent to RNA Pol II inhibition. We therefore conclude that triptolide causes global transcriptional arrest as evidenced by inactivity of RNA polymerases I and II and the subsequent alteration in nuclear sub-structure. PMID:18593926

  15. Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion.

    PubMed

    Krull, Sandra; Dörries, Julia; Boysen, Björn; Reidenbach, Sonja; Magnius, Lars; Norder, Helene; Thyberg, Johan; Cordes, Volker C

    2010-05-19

    Amassments of heterochromatin in somatic cells occur in close contact with the nuclear envelope (NE) but are gapped by channel- and cone-like zones that appear largely free of heterochromatin and associated with the nuclear pore complexes (NPCs). To identify proteins involved in forming such heterochromatin exclusion zones (HEZs), we used a cell culture model in which chromatin condensation induced by poliovirus (PV) infection revealed HEZs resembling those in normal tissue cells. HEZ occurrence depended on the NPC-associated protein Tpr and its large coiled coil-forming domain. RNAi-mediated loss of Tpr allowed condensing chromatin to occur all along the NE's nuclear surface, resulting in HEZs no longer being established and NPCs covered by heterochromatin. These results assign a central function to Tpr as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution.

  16. Characterization Report for the David Witherspoon Screen Art Site

    SciTech Connect

    Phyllis C. Weaver

    2011-01-31

    The U.S. Department of Energy (DOE) Oak Ridge Office (ORO) of Environmental Management (EM) requested the technical assistance of Oak Ridge Institute for Science and Education (ORISE) to characterize a tract of land associated with the David Witherspoon, Incorporated (DWI) Volunteer Equipment and Supply Company (VESC). This tract of land (hereinafter referred to as Screen Arts) is located in the Vestal Community in the 2000-block of Maryville Pike in south Knoxville, Tennessee, as shown in Figure A-1. This tract of land has been used primarily to store salvaged equipment and materials for resale, recycle, or for disposal in the former landfill once operated by DWI. The DWI Site industrial landfill and metal recycling business had been permitted by the Tennessee Division of Radiological Health to accept low-level radiologically contaminated metals. DWI received materials and equipment associated with operations from DOE sites, including those in Oak Ridge, Tennessee; Paducah, Kentucky; and Portsmouth, Ohio. It is likely that items stored at Screen Arts may have contained some residual radiological materials.

  17. SUMOylation regulates the nuclear mobility of CREB binding protein and its association with nuclear bodies in live cells

    SciTech Connect

    Ryan, Colm M.; Kindle, Karin B.; Collins, Hilary M.; Heery, David M.

    2010-01-01

    The lysine acetyltransferase CREB binding protein (CBP) is required for chromatin modification and transcription at many gene promoters. In fixed cells, a large proportion of CBP colocalises to PML or nuclear bodies. Using live cell imaging, we show here that YFP-tagged CBP expressed in HEK293 cells undergoes gradual accumulation in nuclear bodies, some of which are mobile and migrate towards the nuclear envelope. Deletion of a short lysine-rich domain that contains the major SUMO acceptor sites of CBP abrogated its ability to be SUMO modified, and prevented its association with endogenous SUMO-1/PML speckles in vivo. This SUMO-defective CBP showed enhanced ability to co-activate AML1-mediated transcription. Deletion mapping revealed that the SUMO-modified region was not sufficient for targeting CBP to PML bodies, as C-terminally truncated mutants containing this domain showed a strong reduction in accumulation at PML bodies. Fluorescence recovery after photo-bleaching (FRAP) experiments revealed that YFP-CBP{Delta}998-1087 had a retarded recovery time in the nucleus, as compared to YFP-CBP. These results indicate that SUMOylation regulates CBP function by influencing its shuttling between nuclear bodies and chromatin microenvironments.

  18. Transient association of Ku with nuclear substrates characterized using fluorescence photobleaching.

    PubMed

    Rodgers, William; Jordan, Stephen J; Capra, J Donald

    2002-03-01

    The autoantigen Ku, composed of subunits Ku70 and Ku86, is necessary for repair of DNA double-strand breaks by nonhomologous end joining. Similarly, Ku participates in repair of DNA double-strand breaks that occur during V(D)J recombination, and it is therefore required for the development of B and T lymphocytes. Although previous studies have identified the DNA-binding activities of Ku, little is known concerning its dynamics, such as the mobility of Ku in the nucleus and its rate of association with substrates. To address this question, fluorescence photobleaching experiments were performed using HeLa cells and B cells expressing a green fluorescent protein (GFP) fusion construct of either Ku70 or Ku86. The results show that Ku moves rapidly throughout the nucleus even following irradiation of the cells. However, the rate of diffusion of Ku was approximately 100-fold slower than that predicted from its size. Association of Ku-GFP with a filamentous nuclear structure was also evident, and nuclear extraction experiments suggest that this represents nuclear matrix. A central domain of Ku70 containing its DNA-binding and heterodimerization regions and its nuclear localization signal shows that this alone is sufficient for the observed mobility of Ku70-GFP and its association with nuclear matrix. These data suggest the mobility of Ku is characterized by a transient, high flux association with nuclear substrates that includes both DNA and the nuclear matrix and may represent a mechanism for repair of double-strand breaks using the nuclear matrix as a scaffold.

  19. 8. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    8. Historic American Buildings Survey, David Aronow, Photographer circa 1924, LIVING ROOM WITH TIFFANY STAINED GLASS WINDOWS INCLUDING 'FEEDING THE FLAMINGOES,' 'THE FOUR SEASONS,' AND 'THE BATHERS'. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  20. 11. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    11. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 EAST FACADE, PART OF NORTH FACADE, SOUTH DAIRY BARN IN BACKGROUND, WITH FIELD IN FOREGROUND - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  1. 12. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    12. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 EAST FACADE, PART OF NORTH FACADE, SOUTH DAIRY BARN IN BACKGROUND - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  2. 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)

  3. 5. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    5. Historic American Buildings Survey, David Aronow, Photographer circa 1924, DETAIL OF ENTRANCE AND BELLTOWER ON FRONT ELEVATION. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  4. 19. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    19. Historic American Buildings Survey, David Aronow, Photographer circa 1924, INTERIOR OF TIFFANY CHAPEL SHOWING STAINED GLASS WINDOW. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  5. 12. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    12. Historic American Buildings Survey, David Aronow, Photographer circa 1924, VIEW OF THE CENTRAL COURT WITH THE FOUNTAIN AND TIFFANY VASES IN NICHES. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  6. 16. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    16. Historic American Buildings Survey, David Aronow, Photographer circa 1924, TERRACE OVERLOOKING COLD SPRING HARBOR WITH VIEW OF 'TIFFANY TOWER'. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  7. 7. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    7. Historic American Buildings Survey, David Aronow, Photographer circa 1924, DETAIL OF MAIN ENTRANCE WITH COLD SPRING HARBOR IN BACKGROUND. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  8. 11. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    11. Historic American Buildings Survey, David Aronow, Photographer circa 1924, CENTRAL COURT WITH PORTRAIT OF TIFFANY BY SOROLLA. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  9. 20. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    20. Historic American Buildings Survey, David Aronow, Photographer circa 1924, 'THE SPRING' ONE OF SEVEN FOUNTAINS ON TIFFANY ESTATE. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  10. 9. Historic American Buildings Survey, David Aronow, Photographer circa 1924, ...

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

    9. Historic American Buildings Survey, David Aronow, Photographer circa 1924, LIVING ROOM SHOWING LIGHTING FIXTURES OF TIFFANY'S DESIGN. - Laurelton Hall, Laurel Hollow & Ridge Roads, Oyster Bay, Nassau County, NY

  11. 8. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    8. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR LOOKING SOUTH AT HEARTH - Longview Farm, Paint-Carpentry-Blacksmith Shop, Longview Road, Lees Summit, Jackson County, MO

  12. 1. Historic American Buildings Survey David von Riesen, Photographer July ...

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

    1. Historic American Buildings Survey David von Riesen, Photographer July 1965 BARRACKS (West), Left - BARRACKS (East), Right (Combined into New Barn) - Fort Larned, Barracks (West), Larned, Pawnee County, KS

  13. 1. Historic American Buildings Survey David von Riesen, Photographer July ...

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

    1. Historic American Buildings Survey David von Riesen, Photographer July 1965 BARRACKS (West), Left - BARRACKS (East), Right (Combined into New Barn) - Fort Larned, Barracks (East), Larned, Pawnee County, KS

  14. PSL, an S phase-related p55 nuclear antigen, associates transiently with chromatin.

    PubMed

    Barque, J P; Lagaye, S; Bendayan, M; Puvion-Dutilleul, F; Danon, F; Larsen, C J

    1985-03-01

    An S phase-related nuclear 55K antigen, also designated PSL, has been characterized in various mammalian cells, using a human serum from a patient with autoimmune disorders (Barque et al., EMBO j 2 (1983) 743). In this report, we show by immunoelectron microscopy that the p55 protein associates in situ with the chromatin of rat hepatocytes. This association is a transient one, as indirect immunofluorescence studies show that PSL does not bind to individualized metaphase chromosomes. Furthermore, immunoprecipitation tests indicate that the majority of PSL is in the non-chromosomal cell fraction. These results suggest that this nuclear antigen is directly involved in the DNA replication process. PMID:3882438

  15. 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

  16. 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

  17. David Florida Laboratory: Support for mobile satellite communications

    NASA Technical Reports Server (NTRS)

    Dumoulin, Jean-Guy; Mamen, Rolf

    1995-01-01

    The comprehensive integration and environmental (including RF) test facilities of the Canadian Space Agency's David Florida Laboratory (CSA)(DFL) were used extensively for the MSAT Program. Following a description of the facilities, the paper outlines their application to the qualification of the two MSAT satellites following an overview of the test plan. Particular emphasis is given to passive intermodulation measurement (PIM) demands, which for the MSAT satellites, contributed to the need to extend the anechoic chamber. The extended chamber was also used for an EMC test and SAR signature test of the RADARSAT satellite. The DFL's facilities are being used for additional aspects of mobile satellite communications. One shielded anechoic Extra High Frequency (EHF) chamber and associated test equipment are employed predominantly for measuring the performance of the IRIDIUM satellites' Engineering Model Gateway Moveable Antennas (EM)(GMA). Other chambers are used for testing aeronautical antennas on behalf of Inmarsat. Still others combine thermal and PIM testing. The paper concludes with a review of the test requirements of evolving satcom missions such as Inmarsat Aero-1.

  18. Computational image analysis of nuclear morphology associated with various nuclear-specific aging disorders.

    PubMed

    Choi, Siwon; Wang, Wei; Ribeiro, Alexandrew J S; Kalinowski, Agnieszka; Gregg, Siobhan Q; Opresko, Patricia L; Niedernhofer, Laura J; Rohde, Gustavo K; Dahl, Kris Noel

    2011-01-01

    Computational image analysis is used in many areas of biological and medical research, but advanced techniques including machine learning remain underutilized. Here, we used automated segmentation and shape analyses, with pre-defined features and with computer generated components, to compare nuclei from various premature aging disorders caused by alterations in nuclear proteins. We considered cells from patients with Hutchinson-Gilford progeria syndrome (HGPS) with an altered nucleoskeletal protein; a mouse model of XFE progeroid syndrome caused by a deficiency of ERCC1-XPF DNA repair nuclease; and patients with Werner syndrome (WS) lacking a functional WRN exonuclease and helicase protein. Using feature space analysis, including circularity, eccentricity, and solidity, we found that XFE nuclei were larger and significantly more elongated than control nuclei. HGPS nuclei were smaller and rounder than the control nuclei with features suggesting small bumps. WS nuclei did not show any significant shape changes from control. We also performed principle component analysis (PCA) and a geometric, contour based metric. PCA allowed direct visualization of morphological changes in diseased nuclei, whereas standard, feature-based approaches required pre-defined parameters and indirect interpretation of multiple parameters. Both methods yielded similar results, but PCA proves to be a powerful pre-analysis methodology for unknown systems.

  19. Panel session on international perspectives on the future of nuclear power.

    PubMed

    Perkowski, Joseph C

    2011-01-01

    The 2009 National Council on Radiation Protection (NCRP) Annual Meeting provided an opportunity to exchange viewpoints and consider current information regarding the evolution of selected commercial nuclear power trends worldwide. Within the overall topical context of radiation-related regulation, focus was placed on activities in the United Kingdom, Japan, and the United States, although general global developments were reviewed to some extent. This paper provides the reader with a sense of these activities as described by the authors and presenters: David Bennett (Environmental Agency, United Kingdom), Alan Hanson (AREVA), Shojiro Matsuura (Japan Nuclear Safety Research Association), and Alexander Marion (Nuclear Energy Institute).

  20. Obituary: David Q. Wark, 1918-2002

    NASA Astrophysics Data System (ADS)

    McMillin, Larry Max

    2003-12-01

    David Q. Wark, a research meteorologist at the National Environmental Satellite, Data, and Information Service of the National Oceanic and Atmospheric Administration (NOAA/NESDIS) and its predecessor organizations for 55 years, died of cancer 30 July 2002. He will be long remembered for his seminal contributions to the weather satellite program. A pioneer in the use of satellite sensors to provide observations of the Earth's environment for application to weather forecasting and atmospheric science, Dr. Wark was noted for his brilliant insights, dedication, and exceptional scientific achievements. He developed many of the theoretical and experimental techniques on which NOAA's current multi- billion-dollar meteorological satellite program is based. In the 1960's and early 1970's, he and his NOAA colleague Donald Hilleary were the motivating force and principal investigators for the first satellite instruments dedicated to sounding the atmosphere for temperature and water-vapor. These instruments included the Satellite Infra-Red Spectrometer (SIRS)-A and -B and the Vertical Temperature Profile Radiometer (VTPR), which were flown on NASA's Nimbus satellites and NOAA's ITOS-D satellites, respectively. With colleague Henry Fleming, he formulated the radiative transfer equation that quantifies the spectral radiances of the Earth and its atmosphere (measured at satellite altitude) and inverted that equation mathematically to infer the atmospheric temperature profile from satellite-based measurements of those radiances. A difficulty they had to overcome was that the mathematical problem is ill-posed, i.e., it admits of an infinite number of solutions. They arrived at a unique solution via an innovative application of a-priori information on the atmospheric state. This work was described in the landmark 1965 Wark and Fleming paper in the American Meteorological Society's Monthly Weather Review. From that early period until just weeks before his death, Dr. Wark continued

  1. Obituary: David Fulmer Bender, 1913-2004

    NASA Astrophysics Data System (ADS)

    Miller, Sylvia L.

    2004-12-01

    David Fulmer Bender died in San Diego, California, on 13 September 2004, at the age of 91. His heart stopped suddenly while he was dancing. His pioneering work in establishing comprehensive, computer-accessible ephemerides of asteroids and comets found many applications, including the first-ever visit to an asteroid, Gaspra, by an interplanetary spacecraft. Dave was born in Reno, Nevada, on 10 February 1913, to Homer Charles Bender and Susan Bowers Bender. The family moved to Spokane, Washington, while Dave was very young. His father was a civil engineer and a graduate of MIT, who helped design bridges and dams throughout the Northwest, including the Grand Coolie Dam. Dave had a brother, Phillip (now deceased), who was one year younger. Advancing rapidly in the Spokane school system, Dave finished high school when he was 15 years old. At 16 he moved to Pasadena, California, and began his studies at the California Institute of Technology (Caltech). In addition to pursuing his course work, he was active in track and football, a tendency toward physical exercise that stayed with him for the rest of his life. It was probably during these years that Dave heard a lecture by Albert Einstein, as mentioned to colleagues many years later. Dave received a BS degree in physics in 1933, an MS in 1934, and a PhD in 1937, all from Caltech. His dissertation was entitled, "The Index of Refraction of Air in the Photographic Infrared." During his sophomore year he found his way to Pomona College in Claremont, California, where he met his future wife, Elizabeth Boyden at a social gathering. They were married in 1935. Dave's academic career spanned the years from 1937 to 1970, initially at Louisiana State University, Vanderbilt University, and then Fisk. As a life-long pacifist and conscientious objector, Dave served alternate duty during World War II. In 1946 he joined the faculty of the physics department at Whittier College in California, where he became the department chair and

  2. Comparative study and prediction of DNA fragments associated with various elements of the nuclear matrix.

    PubMed

    Glazko, G V; Rogozin, I B; Glazkov, M V

    2001-02-16

    Scaffold/matrix-associated region (S/MAR) sequences are DNA regions that are attached to the nuclear matrix, and participate in many cellular processes. The nuclear matrix is a complex structure consisting of various elements. In this paper we compared frequencies of simple nucleotide motifs in S/MAR sequences and in sequences extracted directly from various nuclear matrix elements, such as nuclear lamina, cores of rosette-like structures, synaptonemal complex. Multivariate linear discriminant analysis revealed significant differences between these sequences. Based on this result we have developed a program, ChrClass (Win/NT version, ftp.bionet.nsc.ru/pub/biology/chrclass/chrclass.zip), for the prediction of the regions associated with various elements of the nuclear matrix in a query sequence. Subsequently, several test samples were analyzed by using two S/MAR prediction programs (a ChrClass and MAR-Finder) and a simple MRS criterion (S/MAR recognition signature) indicating the presence of S/MARs. Some overlap between the predictions of all MAR prediction tools has been found. Simultaneous use of the ChrClass, MRS criterion and MAR-Finder programs may help to obtain a more clearcut picture of S/MAR distribution in a query sequence. In general, our results suggest that the proportion of missed S/MARs is lower for ChrClass, whereas the proportion of wrong S/MARs is lower for MAR-Finder and MRS.

  3. Obituary: David Fulmer Bender, 1913-2004

    NASA Astrophysics Data System (ADS)

    Miller, Sylvia L.

    2004-12-01

    David Fulmer Bender died in San Diego, California, on 13 September 2004, at the age of 91. His heart stopped suddenly while he was dancing. His pioneering work in establishing comprehensive, computer-accessible ephemerides of asteroids and comets found many applications, including the first-ever visit to an asteroid, Gaspra, by an interplanetary spacecraft. Dave was born in Reno, Nevada, on 10 February 1913, to Homer Charles Bender and Susan Bowers Bender. The family moved to Spokane, Washington, while Dave was very young. His father was a civil engineer and a graduate of MIT, who helped design bridges and dams throughout the Northwest, including the Grand Coolie Dam. Dave had a brother, Phillip (now deceased), who was one year younger. Advancing rapidly in the Spokane school system, Dave finished high school when he was 15 years old. At 16 he moved to Pasadena, California, and began his studies at the California Institute of Technology (Caltech). In addition to pursuing his course work, he was active in track and football, a tendency toward physical exercise that stayed with him for the rest of his life. It was probably during these years that Dave heard a lecture by Albert Einstein, as mentioned to colleagues many years later. Dave received a BS degree in physics in 1933, an MS in 1934, and a PhD in 1937, all from Caltech. His dissertation was entitled, "The Index of Refraction of Air in the Photographic Infrared." During his sophomore year he found his way to Pomona College in Claremont, California, where he met his future wife, Elizabeth Boyden at a social gathering. They were married in 1935. Dave's academic career spanned the years from 1937 to 1970, initially at Louisiana State University, Vanderbilt University, and then Fisk. As a life-long pacifist and conscientious objector, Dave served alternate duty during World War II. In 1946 he joined the faculty of the physics department at Whittier College in California, where he became the department chair and

  4. Nuclear envelope-associated endosomes deliver surface proteins to the nucleus.

    PubMed

    Chaumet, Alexandre; Wright, Graham D; Seet, Sze Hwee; Tham, Keit Min; Gounko, Natalia V; Bard, Frederic

    2015-01-01

    Endocytosis directs molecular cargo along three main routes: recycling to the cell surface, transport to the Golgi apparatus or degradation in endolysosomes. Pseudomonas exotoxin A (PE) is a bacterial protein that typically traffics to the Golgi and then the endoplasmic reticulum before translocating to the cytosol. Here we show that a substantial fraction of internalized PE is also located in nuclear envelope-associated endosomes (NAE), which display limited mobility, exhibit a propensity to undergo fusion and readily discharge their contents into the nuclear envelope. Electron microscopy and protein trapping in the nucleus indicate that NAE mediate PE transfer into the nucleoplasm. RNAi screening further revealed that NAE-mediated transfer depends on the nuclear envelope proteins SUN1 and SUN2, as well as the Sec61 translocon complex. These data reveal a novel endosomal route from the cell surface to the nucleoplasm that facilitates the accumulation of extracellular and cell surface proteins in the nucleus. PMID:26356418

  5. An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

    PubMed Central

    Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

    2014-01-01

    Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic

  6. Environmental Problems Associated With Decommissioning The Chernobyl Nuclear Power Plant Cooling Pond

    SciTech Connect

    Farfan, E. B.; Jannik, G. T.; Marra, J. C.; Oskolkov, B. Ya.; Bondarkov, M. D.; Gaschak, S. P.; Maksymenko, A. M.; Maksymenko, V. M.; Martynenko, V. I.

    2009-11-09

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities has been an imperative issue lately. There exist significant experience and generally accepted recommendations on remediation of lands with residual radioactive contamination; however, there are hardly any such recommendations on remediation of cooling ponds that, in most cases, are fairly large water reservoirs. The literature only describes remediation of minor reservoirs containing radioactive silt (a complete closure followed by preservation) or small water reservoirs resulting in reestablishing natural water flows. Problems associated with remediation of river reservoirs resulting in flooding of vast agricultural areas also have been described. In addition, the severity of environmental and economic problems related to the remedial activities is shown to exceed any potential benefits of these activities. One of the large, highly contaminated water reservoirs that require either remediation or closure is Karachay Lake near the MAYAK Production Association in the Chelyabinsk Region of Russia where liquid radioactive waste had been deep well injected for a long period of time. Backfilling of Karachay Lake is currently in progress. It should be noted that secondary environmental problems associated with its closure are considered to be of less importance since sustaining Karachay Lake would have presented a much higher radiological risk. Another well-known highly contaminated water reservoir is the Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond, decommissioning of which is planned for the near future. This study summarizes the environmental problems associated with the ChNPP Cooling Pond decommissioning.

  7. ENVIRONMENTAL PROBLEMS ASSOCIATED WITH DECOMMISSIONING THE CHERNOBYL NUCLEAR POWER PLANT COOLING POND

    SciTech Connect

    Farfan, E.

    2009-09-30

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities has been an imperative issue lately. There exist significant experience and generally accepted recommendations on remediation of lands with residual radioactive contamination; however, there are hardly any such recommendations on remediation of cooling ponds that, in most cases, are fairly large water reservoirs. The literature only describes remediation of minor reservoirs containing radioactive silt (a complete closure followed by preservation) or small water reservoirs resulting in reestablishing natural water flows. Problems associated with remediation of river reservoirs resulting in flooding of vast agricultural areas also have been described. In addition, the severity of environmental and economic problems related to the remedial activities is shown to exceed any potential benefits of these activities. One of the large, highly contaminated water reservoirs that require either remediation or closure is Karachay Lake near the MAYAK Production Association in the Chelyabinsk Region of Russia where liquid radioactive waste had been deep well injected for a long period of time. Backfilling of Karachay Lake is currently in progress. It should be noted that secondary environmental problems associated with its closure are considered to be of less importance since sustaining Karachay Lake would have presented a much higher radiological risk. Another well-known highly contaminated water reservoir is the Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond, decommissioning of which is planned for the near future. This study summarizes the environmental problems associated with the ChNPP Cooling Pond decommissioning.

  8. INTRODUCTION: David Sherrington as a mentor of young scientists

    NASA Astrophysics Data System (ADS)

    Goldbart, Paul M.

    2008-08-01

    How deeply honoured I am to have the opportunity to express my thoughts at this delightful celebration of David's achievements, so far, in his remarkable career. I have been asked to center my remarks on David's contributions to the mentoring and professional development of scientists early in their careers. This is a topic that I am more than happy to reflect on, because it gives me the opportunity to recall the exciting period I spent as one of David's postgraduate students at Imperial College in the early 1980s. It also gives me the chance to publicly express my gratitude to David for the opportunities he created for me at that time, as well as for the interest and care he has shown in my career and well-being ever since, as we have met up and exchanged news and ideas around the world: in New Mexico and Colorado, in Cancun, Paris and Trieste, at numerous March Meetings of the American Physical Society and, of course in London, Oxford, and my home town, Champaign-Urbana, location of the University of Illinois. I have been a member of David's circle for 25 years now, and I would like to tell you a little about how this came to be. Not because of what this says about me, but, rather, because of what it tells you about David and the rich generosity of his spirit and effort when it comes to supporting the underdog. I was indeed one such underdog—and that's putting it charitably—when I first met David in September of 1982, not long before the academic year was to begin. I had heard about the exciting circle of physical and mathematical ideas swirling around the spin glass question during the previous year, which I had spent at the University of California's Los Angeles campus, through an opportunity kindly arranged, as it happens, by Sam Edwards. But I was eager to return to the UK for postgraduate studies and to work on spin glasses, so I simply showed up at David's Imperial College office, unannounced (if I remember correctly). And with his characteristic

  9. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype

    PubMed Central

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis. PMID:27031510

  10. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype.

    PubMed

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis.

  11. Dr. David Sawyer, Mickey Mouse and Dr. David Brown attend a ceremony at Ronald McNair Middle School

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. David Sawyer (left), Superintendent of the Brevard County School District, Mickey Mouse, and Dr. David Brown, a NASA astronaut, attend a tribute to NASA astronaut Ronald McNair held in the gymnasium of Ronald McNair Magnet School in Cocoa, Fla. During the tribute, Walt Disney World presented a portrait of McNair to the school, which had previously been renamed for the fallen astronaut. McNair was one of a crew of seven who lost their lives during an accident following launch of the Space Shuttle Challenger in January 1986.

  12. Instructional Implications of David C. Geary's Evolutionary Educational Psychology

    ERIC Educational Resources Information Center

    Sweller, John

    2008-01-01

    David C. Geary's thesis has the potential to alter our understanding of those aspects of human cognition relevant to instruction. His distinction between biologically primary knowledge that we have evolved to acquire and biologically secondary knowledge that is culturally important, taught in educational institutions and which we have not evolved…

  13. Astronaut David Wolf in medical experiment in SLS-2

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Astronaut David A. Wolf, mission specialist, participates in an experiment that investigates in-space distribution and movement of blood and gas in the pulmonary system. The data gathered during the two-week flight will be compared with results of tests performed on Earth to determine the changes that occur in pulmonary functions.

  14. Q & A with Ed Tech Leaders: Interview with David Dockterman

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.

    2014-01-01

    In this article, Michael F. Shaughnessy, Contributing Editor of this journal, interviews David Dockterman, Chief Architect, Learning Sciences, at Scholastic Education, where he provides guidance on turning research into practical programs. Dockterman was one of the founders of Tom Snyder Productions, a leading educational software developer and…

  15. Can Education Save the World? A Response to David Gruenewald

    ERIC Educational Resources Information Center

    Stables, Andrew

    2004-01-01

    Any commitment to education for sustainability assumes that teaching and learning can reduce or prevent damage to the biosphere. However, such an assumption remains deeply problematic. David Gruenewald's is only one of several possible epistemological positions. This article discusses the variety of such positions, arguing for that which might…

  16. Challenging Texts: Teaching Deliberately--Reading Henry David Thoreau's "Walden"

    ERIC Educational Resources Information Center

    Davis, Andrea

    2011-01-01

    One of the more difficult 19th-century American texts for high school students to read is undoubtedly Henry David Thoreau's "Walden." His erudite allusions, often page-long sentences, and sophisticated sense of the ironic initially leave many students cold. Still, the author encourages them to read amid the din of a cultural cacophony that shouts…

  17. Inside the Classroom of Harvard Law School Professor David Wilkins.

    ERIC Educational Resources Information Center

    Lawrence-Lightfoot, Sara

    1999-01-01

    Examines the teaching methods of David Wilkins, an African American Harvard Law School professor considered an exciting teacher by his students and colleagues. Describes his skill in getting students to attend class, engage in legal thinking, feel comfortable in the classroom, and learn the formal rituals and procedures for the court. (SM)

  18. Empowering Adolescent Readers: Intertextuality in Three Novels by David Almond

    ERIC Educational Resources Information Center

    Latham, Don

    2008-01-01

    In "Skellig," "Kit's Wilderness," and "Clay", David Almond employs various types of intertextuality to enrich his narratives. Through the use of allusion, adaptation, collage, and mise-en-abyme, he encourages his adolescent readers to seek out precursor texts and to consider the interrelationships between these texts and his own. By so doing, he…

  19. From the Ocean's Flotsam, David Wiesner Imagines a Journey

    ERIC Educational Resources Information Center

    Ward, Barbara A.

    2008-01-01

    David Wiesner's 2007 Caldecott Medal-winning "Flotsam" blends the events of everyday life with the surreal. As he often does in his picture books, Wiesner plays with size and scale, opening "Flotsam" with a full-page illustration of a sand crab and the enormous eye behind it before pulling back on the second page to reveal the creature's actual…

  20. David Almond's "Skellig": "A New Vista of Contemplation"?

    ERIC Educational Resources Information Center

    Stewart, Susan Louise

    2009-01-01

    The debates that have arisen regarding Darwin's theories of evolution and Christian views of creation and their place in education in the United States have frequently been extremely heated, resulting in trials, hearings, and laws. This article provides an overview of some of the disagreements and illustrates how David Almond's British novel,…

  1. David Haynes: Chronicler of the African American Middle Class.

    ERIC Educational Resources Information Center

    Barron, Ronald

    1997-01-01

    Profiles writer David Haynes, and discusses his four novels (an award-winning young adult book and three novels for the adult market). Concludes that Haynes' success as a novelist is due to his characters, a healthy dose of humor, and his realistic depiction of a wide range of African American characters without resorting to sensationalism or…

  2. Grade 1 Students Meet David Wiesner's "Three Pigs."

    ERIC Educational Resources Information Center

    Pantaleo, Sylvia

    2002-01-01

    Describes the oral, written, and visual arts responses of a group of Grade 1 children. Discusses first grade children's understandings of and responses to several Radical Change characteristics and metafictive techniques found in David Wiesner's "The Three Pigs" (2001), the 2002 Randolph Caldecott Medal winner. Explores the nature of the literary…

  3. Video from Panel Discussion with Joseph Fraumeni and David Schottenfeld

    Cancer.gov

    Video footage from Panel Discussion with Joseph Fraumeni and David Schottenfeld on Cancer Epidemiology over the Last Half-Century and Thoughts on the Future. The discussion took place on May 11, 2012, when DCEG hosted Dr. Schottenfeld as a Visiting Scholar.

  4. Moral philosophers are moral experts! A reply to David Archard.

    PubMed

    Gordon, John-Stewart

    2014-05-01

    In his article 'Why Moral Philosophers Are Not and Should Not Be Moral Experts' David Archard attempts to show that his argument from common-sense morality is more convincing than other competing arguments in the debate. I examine his main line of argumentation and eventually refute his main argument in my reply.

  5. Life after Death in Poverty: David Treuer's "Little"

    ERIC Educational Resources Information Center

    Stirrup, David

    2005-01-01

    David Treuer's debut novel, "Little" (1995), is set on a Minnesota reservation, centering around a dilapidated housing tract that its small community of residents call "Poverty." Aptly named both for the condition and background of the housing, this name is the first pointer to the type of multifaceted reading that the novel merits. This essay…

  6. David Hoffman's Law School Lectures, 1822-1833.

    ERIC Educational Resources Information Center

    Shaffer, Thomas L.

    1982-01-01

    The Baltimore lawyer David Hoffman (1784-1854), the father of American legal ethics, was also the first of the systematic American legal educators. The history and operation of his law school, the curriculum, and his effective use of the lecture method are described and discussed. (MSE)

  7. Reflections on the Scholarly Contributions of Professor David H. Jonassen

    ERIC Educational Resources Information Center

    Reeves, Thomas C.; Lee, Chwee Beng; Hung, Woei

    2013-01-01

    The six papers in this special issue of "Computers and Education" honoring Professor David H. Jonassen are diverse in nature. They also reflect differing interpretations of the implications of Jonassen's work for research and development focused on instructional models and the factors influencing instruction as well as the directions for future…

  8. STS-69 Mission Commander David M. Walker in white room

    NASA Technical Reports Server (NTRS)

    1995-01-01

    STS-69 Mission Commander David M. Walker chats with white room closeout crew members Bob Saulnier (left), Regulo Villalobos and closeout crew leader Travis Thompson prior to entering the flight deck of the Space Shuttle Endeavour at Launch Pad 39A.

  9. David Samwell (1751-98): surgeon on the Discovery.

    PubMed

    Morris, J S

    2002-07-01

    David Samwell, born in North Wales, was surgeon on the Discovery during the third and last voyage of Captain James Cook. Samwell wrote a biography of Cook and was a distinguished poet. He also served on several more voyages, retiring from the sea aged 45. PMID:12151677

  10. Henry David Thoreau and Martin Luther King, Jr. Lesson Plan.

    ERIC Educational Resources Information Center

    Powell, Brent

    1995-01-01

    Presents a five-lesson, high school instructional unit on the ideas and activities of Henry David Thoreau and Martin Luther King, Jr. Includes student objectives, step-by-step instructional procedures, and discussion questions. Provides quotations by Thoreau and King. (CFR)

  11. Child Welfare Research and Training: A Response to David Stoesz

    ERIC Educational Resources Information Center

    Smith, Brenda D.; Vandiver, Vikki L.

    2016-01-01

    In this response to David Stoesz' critique, "The Child Welfare Cartel," the authors agree that child welfare research and training must be improved. The authors disagree, however, with Stoesz' critique of social work education, his assessment of the most-needed forms of child welfare research, and his depiction of the goals and…

  12. Nucleus accumbens associated 1 is recruited within the promyelocytic leukemia nuclear body through SUMO modification

    PubMed Central

    Tatemichi, Yoshinori; Shibazaki, Masahiko; Yasuhira, Shinji; Kasai, Shuya; Tada, Hiroshi; Oikawa, Hiroki; Suzuki, Yuji; Takikawa, Yasuhiro; Masuda, Tomoyuki; Maesawa, Chihaya

    2015-01-01

    Nucleus accumbens associated 1 (NACC1) is a cancer-associated BTB/POZ (pox virus and zinc finger/bric-a-brac tramtrack broad complex) gene, and is involved in several cellular functions in neurons, cancer and stem cells. Some of the BTB/POZ proteins associated with cancer biology are SUMOylated, which appears to play an important role in transcription regulation. We show that NACC1 is SUMOylated on a phylogenetically conserved lysine (K167) out of three consensus SUMOylation motif sites. Amino acid substitution in the SIM sequence (SIM/M) within the BTB/POZ domain partially reduced K167 SUMOylation activity of NACC1. Overexpression of GFP-NACC1 fusion protein leads to formation of discrete nuclear foci similar to promyelocytic leukemia nuclear bodies (PML-NB), which colocalized with SUMO paralogues (SUMO1/2/3). Both NACC1 nuclear body formation and colocalization with SUMO paralogues were completely suppressed in the GFP-NACC1-SIM/M mutant, whereas they were partially maintained in the NACC1 K167R mutant. Confocal immunofluorescence analysis showed that endogenous and exogenous NACC1 proteins colocalized with endogenous PML protein. A pull-down assay revealed that the consensus motifs of the SUMO acceptor site at K167 and the SIM within the BTB/POZ domain were both necessary for efficient binding to PML protein. Our study demonstrates that NACC1 can be modified by SUMO paralogues, and cooperates with PML protein. PMID:25891951

  13. Nuclear localization of the dystrophin-associated protein α-dystrobrevin through importin α2/β1 is critical for interaction with the nuclear lamina/maintenance of nuclear integrity.

    PubMed

    Aguilar, Areli; Wagstaff, Kylie M; Suárez-Sánchez, Rocío; Zinker, Samuel; Jans, David A; Cisneros, Bulmaro

    2015-05-01

    Although α-dystrobrevin (DB) is assembled into the dystrophin-associated protein complex, which is central to cytoskeletal organization, it has also been found in the nucleus. Here we delineate the nuclear import pathway responsible for nuclear targeting of α-DB for the first time, together with the importance of nuclear α-DB in determining nuclear morphology. We map key residues of the nuclear localization signal of α-DB within the zinc finger domain (ZZ) using various truncated versions of the protein, and site-directed mutagenesis. Pulldown, immunoprecipitation, and AlphaScreen assays showed that the importin (IMP) α2/β1 heterodimer interacts with high affinity with the ZZ domain of α-DB. In vitro nuclear import assays using antibodies to specific importins, as well as in vivo studies using siRNA or a dominant negative importin construct, confirmed the key role of IMPα2/β1 in α-DB nuclear translocation. Knockdown of α-DB expression perturbed cell cycle progression in C2C12 myoblasts, with decreased accumulation of cells in S phase and, significantly, altered localization of lamins A/C, B1, and B2 with accompanying gross nuclear morphology defects. Because α-DB interacts specifically with lamin B1 in vivo and in vitro, nuclear α-DB would appear to play a key role in nuclear shape maintenance through association with the nuclear lamina.

  14. Identification of the gene encoding the major latency-associated nuclear antigen of the Kaposi's sarcoma-associated herpesvirus.

    PubMed Central

    Kedes, D H; Lagunoff, M; Renne, R; Ganem, D

    1997-01-01

    Over 85% of patients with Kaposi's sarcoma (KS) are seropositive for antibodies to the latency-associated nuclear antigen (LANA) expressed in B cell lines infected with Kaposi's sarcoma-associated herpesvirus (KSHV). The presence of antibodies to LANA strongly correlates with the risk of developing the disease. However, the identity of the protein(s) comprising LANA and the corresponding gene(s) has remained unclear. To identify potential latent gene candidates for LANA, we probed total RNA extracted from BCBL-1 cells (a B cell line latently infected with KSHV) using lambda clones that span the KSHV genome. One region encoding latent transcripts spanned KSHV open reading frames (orfs) 71 (K13), 72 (v-cyclin), and 73. Among these, however, only orf 73, when expressed in heterologous mammalian cell systems, reacted with KSHV antibody-positive human sera, resulting in a punctate nuclear staining pattern reminiscent of LANA in BCBL-1 cells. Furthermore, extracts from cells expressing the orf 73 protein product specifically blocked the binding of KS patient antibodies to LANA. Finally, seroreactivity with recombinant orf 73 protein exactly paralleled reactivity with classical LANA as expressed in BCBL-1 cells, both in KS patients and in other groups. Together, these data support the identification of KSHV orf 73 as the gene encoding the dominant immunogenic component of LANA. PMID:9366576

  15. Characterization of a novel Dp71 dystrophin-associated protein complex (DAPC) present in the nucleus of HeLa cells: Members of the nuclear DAPC associate with the nuclear matrix

    SciTech Connect

    Fuentes-Mera, Lizeth; Rodriguez-Munoz, Rafael; Gonzalez-Ramirez, Ricardo; Garcia-Sierra, Francisco; Gonzalez, Everardo; Mornet, Dominique; Cisneros, Bulmaro . E-mail: bcisnero@cinvestav.mx

    2006-10-01

    Dystrophin is an essential component in the assembly and maintenance of the dystrophin-associated protein complex (DAPC), which includes members of the dystroglycan, syntrophin, sarcoglycan and dystrobrevin protein families. Distinctive complexes have been described in the cell membrane of different tissues and cultured cells. In this work, we report the identification and characterization of a novel DAPC present in the nuclei of HeLa cells, which contains dystrophin Dp71 as a key component. Using confocal microscopy and cell fractionation analyses, we found the presence of Dp71, {beta}-sarcoglycan, {beta}-dystroglycan, {alpha}- and {beta}-syntrophin, {alpha}1- and {beta}-dystrobrevin and nNOS in the nuclei of HeLa cells. Furthermore, we demonstrated by co-immunoprecipitation experiments that most of these proteins form a complex in the nuclear compartment. Next, we analyze the possible association of the nuclear DAPC with the nuclear matrix. We found the presence of Dp71, {beta}-dystroglycan, nNOS, {beta}-sarcoglycan, {alpha}/{beta} syntrophin, {alpha}1-dystrobrevin and {beta}-dystrobrevin in the nuclear matrix protein fractions and in situ nuclear matrix preparations from HeLa cells. Moreover, we found that Dp71, {beta}-dystroglycan and {beta}-dystrobrevin co-immunoprecipitated with the nuclear matrix proteins lamin B1 and actin. The association of members of the nuclear DAPC with the nuclear matrix indicates that they may work as scaffolding proteins involved in nuclear architecture.

  16. A new gene mapping resource: Interspecies hybrids between Pere David`s deer (Elaphurus davidianus) and red deer (Cervus elaphus)

    SciTech Connect

    Tate, M.L.; Mathias, H.C.; Penty, J.M.; Hill, D.F.; Fennessy, P.F.; Dodds, K.G.

    1995-03-01

    Three male F{sub 1} hybrids between Pere David`s deer and red deer were mated to red deer to produce 143 backcross calves. The pedigrees are a rare example of a fertile hybrid between evolutionarily divergent species. We examined the use of these families for genetic mapping of evolutionarily conserved (Type I) loci by testing for genetic linkage between five species-specific protein variants and 12 conserved DNA probes. Two probes were homologous, and the remainder syntenic, to the protein coding loci in cattle or humans. Using six restriction enzymes, each DNA probe detected one or more restriction fragments specific to Pere David`s deer. Linkage analyses among the species-specific variants placed the loci into four linkage groups within which linkage between adjacent loci and gene order was supported by a LOD > 3. Southern and protein analysis of LDHA and ALB provided identical segregation data. These linkage groups were consistent with the cattle gene map and provide new information for comparing the gene maps of ruminants, humans and mice. The deer hybrids are an important new resource that can contribute to the comparative analysis of the mammalian genome. 68 refs., 2 figs., 2 tabs.

  17. Human Homolog of Drosophila Ariadne (HHARI) is a marker of cellular proliferation associated with nuclear bodies

    SciTech Connect

    Elmehdawi, Fatima; Wheway, Gabrielle; Szymanska, Katarzyna; Adams, Matthew; High, Alec S.; Johnson, Colin A.; Robinson, Philip A.

    2013-02-01

    HHARI (also known as ARIH1) is an ubiquitin-protein ligase and is the cognate of the E2, UbcH7 (UBE2L3). To establish a functional role for HHARI in cellular proliferation processes, we performed a reverse genetics screen that identified n=86/522 (16.5%) ubiquitin conjugation components that have a statistically significant effect on cell proliferation, which included HHARI as a strong hit. We then produced and validated a panel of specific antibodies that establish HHARI as both a nuclear and cytoplasmic protein that is expressed in all cell types studied. HHARI was expressed at higher levels in nuclei, and co-localized with nuclear bodies including Cajal bodies (p80 coilin, NOPP140), PML and SC35 bodies. We confirmed reduced cellular proliferation after ARIH1 knockdown with individual siRNA duplexes, in addition to significantly increased levels of apoptosis, an increased proportion of cells in G2 phase of the cell cycle, and significant reductions in total cellular RNA levels. In head and neck squamous cell carcinoma biopsies, there are higher levels of HHARI expression associated with increased levels of proliferation, compared to healthy control tissues. We demonstrate that HHARI is associated with cellular proliferation, which may be mediated through its interaction with UbcH7 and modification of proteins in nuclear bodies. -- Highlights: ► We produce and validate new antibody reagents for the ubiquitin-protein ligase HHARI. ► HHARI colocalizes with nuclear bodies including Cajal, PML and SC35 bodies. ► We establish new functions in cell proliferation regulation for HHARI. ► Increased HHARI expression associates with squamous cell carcinoma and proliferation.

  18. Intraspecific host selection of Père David's deer by cattle egrets in Dafeng, China.

    PubMed

    Fernandez, Eve V; Li, Zhongqiu; Zheng, Wei; Ding, Yuhua; Sun, Daming; Che, Ye

    2014-06-01

    Studies have focused on foraging ecology of cattle egrets (Bubulcus ibis) and their selection of ungulate host species. However, few studies have been conducted at intraspecific levels, such as the sex/age class of a specific ungulate. In this study, the foraging behavior and intraspecific host selection of cattle egrets associated with Père David's deer (Elaphurus davidianus) were investigated at the Dafeng National Nature Reserve, China in summer 2011 and 2012. Egret-deer pairing status was analyzed and intraspecific host selection index was calculated. Cattle egrets preferred to feed with female deer compared with male deer and fawns. In contrast to solitary birds, cattle egrets following a deer benefited from a relatively low vigilance output, high foraging success, low energy expenditure, and high total foraging yields. These egrets also maximized benefits when they followed female deer compared with male deer and fawns. Our results further indicated that egrets likely preferred females because of the appropriate moving speed that allowed these egrets to follow and forage sufficiently and effectively. The males of Père David's deer were possibly more aggressive than the females during the rutting season, causing egrets to experience difficulty in accompaniment and feeding. Fawns were not preferred because they were usually motionless and insufficiently large to stir more insects. We did not find any behavioral differences in vigilance and feeding between juveniles and adults. Our results suggested that cattle egrets could obtain significant benefits from their association with Père David's deer, and these benefits were maximized when they followed female deer. This article is part of a Special Issue entitled: insert SI title.

  19. Potential Signatures of Semi-volatile Compounds Associated With Nuclear Processing

    SciTech Connect

    Probasco, Kathleen M.; Birnbaum, Jerome C.; Maughan, A. D.

    2002-06-01

    Semi-volatile chemicals associated with nuclear processes (e.g., the reprocessing of uranium to produce plutonium for nuclear weapons, or the separation of actinides from processing waste streams), can provide sticky residues or signatures that will attach to piping, ducting, soil, water, or other surface media. Volatile compounds, that are more suitable for electro-optical sensing, have been well studied. However, the semi-volatile compounds have not been well documented or studied. A majority of these semi-volatile chemicals are more robust than typical gaseous or liquid chemicals and can have lifetimes of several weeks, months, or years in the environment. However, large data gaps exist concerning these potential signature compounds and more research is needed to fill these data gaps so that important signature information is not overlooked or discarded. This report investigates key semi-volatile compounds associated with nuclear separations, identifies available chemical and physical properties, and discusses the degradation products that would result from hydrolysis, radiolysis and oxidation reactions on these compounds.

  20. Proneural proteins Achaete and Scute associate with nuclear actin to promote formation of external sensory organs.

    PubMed

    Hsiao, Yun-Ling; Chen, Yu-Ju; Chang, Yi-Jie; Yeh, Hsiao-Fong; Huang, Yi-Chun; Pi, Haiwei

    2014-01-01

    Basic helix-loop-helix (bHLH) proneural proteins promote neurogenesis through transcriptional regulation. Although much is known about the tissue-specific regulation of proneural gene expression, how proneural proteins interact with transcriptional machinery to activate downstream target genes is less clear. Drosophila proneural proteins Achaete (Ac) and Scute (Sc) induce external sensory organ formation by activating neural precursor gene expression. Through co-immunoprecipitation and mass spectrometric analyses, we found that nuclear but not cytoplasmic actin associated with the Ac and Sc proteins in Drosophila S2 cells. Daughterless (Da), the common heterodimeric partner of Drosophila bHLH proteins, was observed to associate with nuclear actin through proneural proteins. A yeast two-hybrid assay revealed that the binding specificity between actin and Ac or Sc was conserved in yeast nuclei without the presence of additional Drosophila factors. We further show that actin is required in external sensory organ formation. Reduction in actin gene activity impaired proneural-protein-dependent expression of the neural precursor genes, as well as formation of neural precursors. Furthermore, increased nuclear actin levels, obtained by expression of nucleus-localized actin, elevated Ac-Da-dependent gene transcription as well as Ac-mediated external sensory organ formation. Taken together, our in vivo and in vitro observations suggest a novel link for actin in proneural-protein-mediated transcriptional activation and neural precursor differentiation.

  1. Gene associations: true romance or chance meeting in a nuclear neighborhood?

    PubMed

    Lawrence, Jeanne B; Clemson, Christine M

    2008-09-22

    Many recent studies have raised interest in the nuclear associations of coregulated genes from different chromosomes, often evoking interpretations of gene-gene interactions, communication, and even "romance." However, in some cases, the associations may be indirect and infrequent and may reflect the segregation of active and inactive genes into different nuclear compartments. The study by Brown et al. (see p. 1083 of this issue) reports that the apparent association of erythroid genes is not a direct interaction nor colocalization to one tiny transcription factory but arises as a result of the known clustering of many active genes with larger splicing factor-rich speckles (a.k.a., SC35-defined domains). This clustering appears largely stochastic but is impacted by the chromosomal neighborhood of the gene as well as its transcriptional status. The study adds a new twist by examining the same gene in a foreign chromosomal context, providing evidence that this impacts a gene's propensity to form gene-domain (or apparent gene-gene) associations within nuclei.

  2. The nuclear membrane-associated honeycomb structure of the unicellular organism Amoeba proteus: on the search for homologies with the nuclear lamina of metazoa.

    PubMed

    Schmidt, M; Grossmann, U; Krohne, G

    1995-07-01

    In the protozoon Amoeba proteus, a complex and highly organized structure with the morphology of a honeycomb is associated with the nucleoplasmic surface of the nuclear membrane. We have tested whether this structure exhibits similarity to the nuclear lamina of metazoic organisms. First, we have shown that the honeycomb layer is composed of 3 to 5 nm thick protein fibrils resistant to treatment with detergent, high salt, and digestion with nucleases, thus possessing properties typical for karyoskeletal elements. However, in contrast to the meshwork of lamin filaments in somatic cells of metazoic organisms, the honeycomb layer is not tightly anchored to the nucleoplasmic side of pore complexes, or to the inner nuclear membrane. Second, in microinjection experiments we investigated whether fluorescently labeled lamins of Xenopus laevis (lamins A and LI) and Drosophila melanogaster (lamin Dmo) were able to associate in vivo with the Amoeba proteus honeycomb structure. In microinjected amoeba these three lamins were efficiently transported into the nucleus, but did not associate with the nuclear envelope. Our results suggest that the Amoeba proteus nuclear envelope, including the honeycomb layer, does not contain proteins exhibiting high homologies to lamins of metazoan species thus preventing the localized assembly of microinjected lamins along the nuclear periphery.

  3. THE ATTRACTIVENESS OF MATERIAS ASSOCIATED WITH THORIUM-BASED NUCLEAR FUEL CYCLES FOR PHWRS

    SciTech Connect

    Prichard, Andrew W.; Niehus, Mark T.; Collins, Brian A.; Bathke, Charles G.; Ebbinghaus, Bartley B.; Hase, Kevin R.; Sleaford, Brad W.; Robel, Martin; Smith, Brian W.

    2011-07-17

    This paper reports the continued evaluation of the attractiveness of materials mixtures containing special nuclear materials (SNM) associated with thorium based nuclear fuel cycles. Specifically, this paper examines a thorium fuel cycle in which a pressurized heavy water reactor (PHWR) is fueled with mixtures of natural uranium/233U/thorium. This paper uses a PHWR fueled with natural uranium as a base fuel cycle, and then compares material attractiveness of fuel cycles that use 233U/thorium salted with natural uranium. The results include the material attractiveness of fuel at beginning of life (BoL), end of life (EoL), and the number of fuel assemblies required to collect a bare critical mass of plutonium or uranium. This study indicates what is required to render the uranium as having low utility for use in nuclear weapons; in addition, this study estimates the increased number of assemblies required to accumulate a bare critical mass of plutonium that has a higher utility for use in nuclear weapons. This approach identifies that some fuel cycles may be easier to implement the International Atomic Energy Agency (IAEA) safeguards approach and have a more effective safeguards by design outcome. For this study, approximately one year of fuel is required to be reprocessed to obtain one bare critical mass of plutonium. Nevertheless, the result of this paper suggests that all spent fuel needs to be rigorously safeguarded and provided with high levels of physical protection. This study was performed at the request of the United States Department of Energy /National Nuclear Security Administration (DOE/NNSA). The methodology and key findings will be presented.

  4. Invariant Delineation of Nuclear Architecture in Glioblastoma Multiforme for Clinical and Molecular Association

    PubMed Central

    Han, Ju; Borowsky, Alexander; Loss, Leandro; Gray, Joe W.; Spellman, Paul T.

    2013-01-01

    Automated analysis of whole mount tissue sections can provide insights into tumor subtypes and the underlying molecular basis of neoplasm. However, since tumor sections are collected from different laboratories, inherent technical and biological variations impede analysis for very large datasets such as The Cancer Genome Atlas (TCGA). Our objective is to characterize tumor histopathology, through the delineation of the nuclear regions, from hematoxylin and eosin (H&E) stained tissue sections. Such a representation can then be mined for intrinsic subtypes across a large dataset for prediction and molecular association. Furthermore, nuclear segmentation is formulated within a multi-reference graph framework with geodesic constraints, which enables computation of multidimensional representations, on a cell-by-cell basis, for functional enrichment and bioinformatics analysis. Here, we present a novel method, Multi-Reference Graph Cut (MRGC), for nuclear segmentation that overcomes technical variations associated with sample preparation by incorporating prior knowledge from manually annotated reference images and local image features. The proposed approach has been validated on manually annotated samples and then applied to a dataset of 377 Glioblastoma Multiforme (GBM) whole slide images from 146 patients. For the GBM cohort, multidimensional representation of the nuclear features and their organization have identified (i) statistically significant subtypes based on several morphometric indices, (ii) whether each subtype can be predictive or not, and (iii) that the molecular correlates of predictive subtypes are consistent with the literature. Data and intermediaries for a number of tumor types (GBM, low grade glial, and kidney renal clear carcinoma) are available at: http://tcga.lbl.gov for correlation with TCGA molecular data. The website also provides an interface for panning and zooming of whole mount tissue sections with/without overlaid segmentation results for

  5. Invariant delineation of nuclear architecture in glioblastoma multiforme for clinical and molecular association.

    PubMed

    Chang, Hang; Han, Ju; Borowsky, Alexander; Loss, Leandro; Gray, Joe W; Spellman, Paul T; Parvin, Bahram

    2013-04-01

    Automated analysis of whole mount tissue sections can provide insights into tumor subtypes and the underlying molecular basis of neoplasm. However, since tumor sections are collected from different laboratories, inherent technical and biological variations impede analysis for very large datasets such as The Cancer Genome Atlas (TCGA). Our objective is to characterize tumor histopathology, through the delineation of the nuclear regions, from hematoxylin and eosin (H&E) stained tissue sections. Such a representation can then be mined for intrinsic subtypes across a large dataset for prediction and molecular association. Furthermore, nuclear segmentation is formulated within a multi-reference graph framework with geodesic constraints, which enables computation of multidimensional representations, on a cell-by-cell basis, for functional enrichment and bioinformatics analysis. Here, we present a novel method, multi-reference graph cut (MRGC), for nuclear segmentation that overcomes technical variations associated with sample preparation by incorporating prior knowledge from manually annotated reference images and local image features. The proposed approach has been validated on manually annotated samples and then applied to a dataset of 377 Glioblastoma Multiforme (GBM) whole slide images from 146 patients. For the GBM cohort, multidimensional representation of the nuclear features and their organization have identified 1) statistically significant subtypes based on several morphometric indexes, 2) whether each subtype can be predictive or not, and 3) that the molecular correlates of predictive subtypes are consistent with the literature. Data and intermediaries for a number of tumor types (GBM, low grade glial, and kidney renal clear carcinoma) are available at: http://tcga.lbl.gov for correlation with TCGA molecular data. The website also provides an interface for panning and zooming of whole mount tissue sections with/without overlaid segmentation results for quality

  6. Nuclear COMMD1 Is Associated with Cisplatin Sensitivity in Ovarian Cancer

    PubMed Central

    Wisman, G. Bea A.; Duiker, Evelien; Reyners, Anna K. L.; van der Zee, Ate G. J.; van de Sluis, Bart; van Vugt, Marcel A. T. M.

    2016-01-01

    Copper metabolism MURR1 domain 1 (COMMD1) protein is a multifunctional protein, and its expression has been correlated with patients’ survival in different types of cancer. In vitro studies revealed that COMMD1 plays a role in sensitizing cancer cell lines to cisplatin, however, the mechanism and its role in platinum sensitivity in cancer has yet to be established. We evaluated the role of COMMD1 in cisplatin sensitivity in A2780 ovarian cancer cells and the relation between COMMD1 expression and response to platinum-based therapy in advanced stage high-grade serous ovarian cancer (HGSOC) patients. We found that elevation of nuclear COMMD1 expression sensitized A2780 ovarian cancer cells to cisplatin-mediated cytotoxicity. This was accompanied by a more effective G2/M checkpoint, and decreased protein expression of the DNA repair gene BRCA1, and the apoptosis inhibitor BCL2. Furthermore, COMMD1 expression was immunohistochemically analyzed in two tissue micro-arrays (TMAs), representing a historical cohort and a randomized clinical trial-based cohort of advanced stage HGSOC tumor specimens. Expression of COMMD1 was observed in all ovarian cancer samples, however, specifically nuclear expression of COMMD1 was only observed in a subset of ovarian cancers. In our historical cohort, nuclear COMMD1 expression was associated with an improved response to chemotherapy (OR = 0.167; P = 0.038), although this association could not be confirmed in the second cohort, likely due to sample size. Taken together, these results suggest that nuclear expression of COMMD1 sensitize ovarian cancer to cisplatin, possibly by modulating the G2/M checkpoint and through controlling expression of genes involved in DNA repair and apoptosis. PMID:27788210

  7. Expansion and apparent fluidity decrease of nuclear membranes induced by low Ca/Mg. Modulation of nuclear membrane lipid fluidity by the membrane-associated nuclear matrix proteins?

    PubMed Central

    1978-01-01

    Macronuclei isolated from Tetrahymena are contracted in form (average diameter: 10.2 micron) at a final Ca/Mg (3:2)concentration of 5 mM. Lowering the ion concentration to 1 mM induces an expansion of the average nuclear diameter to 12.2 micron. Both contracted and expanded nuclei are surrounded by a largely intact nuclear envelope as revealed by thin-sectioning electron microscopy. Nuclear swelling is accompanied by an expansion of the nuclear envelope as indicated by the decrease in the frequency of nuclear pore complexes from 52.6 to 42.1 pores/micron2 determined by freeze-etch electron microscopy. Contracted nuclear membranes reveal particle-devoid areas (average size: 0.21 micron2) on 59% of their fracture faces at the optimal growth temperature of 28 degrees C. About three-fifths of the number of these smooth areas disappear upon nuclear membrane expansion. Electron spin resonance using 5-doxylstearic acid as a spin label indicates a higher lipid fluidity in contracted than in expa,ded nuclear membranes. Moreover, a thermotropic lipid clustering occurs at approximately 17 degrees C only in expanded nuclear membranes. In contrast to the nuclear membrane- bound lipids, free lipids extracted from the nuclei rigidify with increasing Ca/Mg concentrations. Our findings are compatible with the view that the peripheral layer of the fundamental nuclear protein- framework, the so-called nuclear matrix, can modulate, inter alia, the lipid distribution and fluidity, respectively, in nuclear membranes. We suggest that a contraction of the nuclear matrix's peripheral layer induces a contraction of the nuclear membranes which, in turn, leads to an isothermic lateral lipid segregation within nuclear membranes. PMID:102650

  8. Magen David Adom--the EMS in Israel.

    PubMed

    Ellis, Daniel Y; Sorene, Eliot

    2008-01-01

    Israel is a small country with a population of around 7 million. The sole EMS provider for Israel is Magen David Adom (MDA) (translated as 'Red Shield of David'). MDA also carries out the functions of a National Society (similar to the Red Cross) and provides all the blood and blood product services for the country. Nationwide, the organisation responds to over 1000 emergency calls a day and uses doctors, paramedics, emergency medical technicians and volunteers. Local geopolitics has meant that MDA has to be prepared for anything from everyday emergency calls to suicide bombings and regional wars. MDA also prides itself in being able to rapidly assemble and dispatch mobile aid teams to scenes of international disasters. Such a broad range of activities is unusual for a single EMS organisation. PMID:17767990

  9. Magen David Adom--the EMS in Israel.

    PubMed

    Ellis, Daniel Y; Sorene, Eliot

    2008-01-01

    Israel is a small country with a population of around 7 million. The sole EMS provider for Israel is Magen David Adom (MDA) (translated as 'Red Shield of David'). MDA also carries out the functions of a National Society (similar to the Red Cross) and provides all the blood and blood product services for the country. Nationwide, the organisation responds to over 1000 emergency calls a day and uses doctors, paramedics, emergency medical technicians and volunteers. Local geopolitics has meant that MDA has to be prepared for anything from everyday emergency calls to suicide bombings and regional wars. MDA also prides itself in being able to rapidly assemble and dispatch mobile aid teams to scenes of international disasters. Such a broad range of activities is unusual for a single EMS organisation.

  10. The human TREX-2 complex is stably associated with the nuclear pore basket.

    PubMed

    Umlauf, David; Bonnet, Jacques; Waharte, François; Fournier, Marjorie; Stierle, Matthieu; Fischer, Benoit; Brino, Laurent; Devys, Didier; Tora, László

    2013-06-15

    In eukaryotes, mRNA export involves many evolutionarily conserved factors that carry the nascent transcript to the nuclear pore complex (NPC). The THO/TREX complex couples transcription to mRNA export and recruits the mRNA export receptor NXF1 for the transport of messenger ribonucleoprotein particles (mRNP) to the NPC. The transcription and export complex 2 (TREX-2) was suggested to interact with NXF1 and to shuttle between transcription sites and the NPC. Here, we characterize the dynamics of human TREX-2 and show that it stably associates with the NPC basket. Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription. Differential profiles of mRNA nuclear accumulation reveal that TREX-2 functions similarly to basket nucleoporins, but differently from NXF1. Thus, our results show that TREX-2 is an NPC-associated complex in mammalian cells and suggest that it is involved in putative NPC basket-related functions.

  11. STS-86 Mission Specialist David Wolf in white room

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-86 Mission Specialist David A. Wolf, at center facing camera, prepares to enter the Space Shuttle Atlantis at Launch Pad 39A, with the assistance of Rick Welty, in foreground at center, United Space Alliance (USA) orbiter vehicle closeout chief; and closeout team members, in background from left, Jim Davis, NASA quality assurance specialist; and George Schramm, USA mechanical technician. STS-86 Mission Specialist Vladimir Georgievich Titov, in foreground at far left, is awaiting his turn.

  12. About David Ruelle, After His 80th Birthday

    NASA Astrophysics Data System (ADS)

    Gallavotti, Giovanni

    2016-05-01

    This is, with minor modifications, a text read at the 114th Statistical Mechanics meeting, in honor of D. Ruelle and Y. Sinai, at Rutgers, Dec. 13-15, 2015. It does not attempt to analyze, or not even just quote, all works of David Ruelle; I discuss, as usual in such occasions, a few among his works with which I have most familiarity and which were a source of inspiration for me.

  13. David Nelson, MD, MPH | Division of Cancer Prevention

    Cancer.gov

    Dr. David E Nelson is the Director of the Cancer Prevention Fellowship Program (CPFP) Branch in the National Cancer Institute's Division of Cancer Prevention. The CPFP is an internationally renowned postdoctoral program designed to train early career scientific researchers and leaders in the field of cancer prevention. Dr. Nelson came to the CPFP in 2008 after working at the Centers for Disease Control and Prevention in Atlanta for many years. |

  14. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists

    PubMed Central

    Huang, Da Wei; Sherman, Brad T; Tan, Qina; Collins, Jack R; Alvord, W Gregory; Roayaei, Jean; Stephens, Robert; Baseler, Michael W; Lane, H Clifford; Lempicki, Richard A

    2007-01-01

    The DAVID Gene Functional Classification Tool uses a novel agglomeration algorithm to condense a list of genes or associated biological terms into organized classes of related genes or biology, called biological modules. This organization is accomplished by mining the complex biological co-occurrences found in multiple sources of functional annotation. It is a powerful method to group functionally related genes and terms into a manageable number of biological modules for efficient interpretation of gene lists in a network context. PMID:17784955

  15. Super-resolution imaging of nuclear import of adeno-associated virus in live cells

    PubMed Central

    Kelich, Joseph M; Ma, Jiong; Dong, Biao; Wang, Qizhao; Chin, Mario; Magura, Connor M; Xiao, Weidong; Yang, Weidong

    2015-01-01

    Adeno-associated virus (AAV) has been developed as a promising human gene therapy vector. Particularly, recombinant AAV vector (rAAV) achieves its transduction of host cells by crossing at least three physiological barriers including plasma membrane, endosomal membrane, and nuclear envelope (NE). So far, the AAV transduction mechanism has not been explored thoroughly at the single viral particle level. In this study, we employed high-speed super-resolution single-point edge-excitation sub-diffraction (SPEED) microscopy to map the events of single rAAV2 particles infecting live human cells with an unprecedented spatiotemporal resolution of 9–12 nm and 2–20 ms. Data reveal that rAAV2 particles are imported through nuclear pore complexes (NPCs) rather than nuclear membrane budding into the nucleus. Moreover, approximately 17% of the rAAV2 molecules starting from the cytoplasm successfully transverse the NPCs to reach the nucleoplasm, revealing that the NPCs act as a strict selective step for AAV delivery. This study lastly suggests a new pathway to improve AAV vectors for human gene therapy. PMID:26665132

  16. AIRE-induced apoptosis is associated with nuclear translocation of stress sensor protein GAPDH

    SciTech Connect

    Liiv, Ingrid; Haljasorg, Uku; Kisand, Kai; Maslovskaja, Julia; Laan, Martti; Peterson, Paert

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer AIRE induces apoptosis in epithelial cells. Black-Right-Pointing-Pointer CARD domain of AIRE is sufficient for apoptosis induction. Black-Right-Pointing-Pointer AIRE induced apoptosis involves GAPDH translocation to the nuclei. Black-Right-Pointing-Pointer Deprenyl inhibits AIRE induced apoptosis. -- Abstract: AIRE (Autoimmune Regulator) has a central role in the transcriptional regulation of self-antigens in medullary thymic epithelial cells, which is necessary for negative selection of autoreactive T cells. Recent data have shown that AIRE can also induce apoptosis, which may be linked to cross-presentation of these self-antigens. Here we studied AIRE-induced apoptosis using AIRE over-expression in a thymic epithelial cell line as well as doxycycline-inducible HEK293 cells. We show that the HSR/CARD domain in AIRE together with a nuclear localization signal is sufficient to induce apoptosis. In the nuclei of AIRE-positive cells, we also found an increased accumulation of a glycolytic enzyme, glyceraldehyde-3-phosphate (GAPDH) reflecting cellular stress and apoptosis. Additionally, AIRE-induced apoptosis was inhibited with an anti-apoptotic agent deprenyl that blocks GAPDH nitrosylation and nuclear translocation. We propose that the AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells.

  17. Super-resolution imaging of nuclear import of adeno-associated virus in live cells.

    PubMed

    Kelich, Joseph M; Ma, Jiong; Dong, Biao; Wang, Qizhao; Chin, Mario; Magura, Connor M; Xiao, Weidong; Yang, Weidong

    2015-01-01

    Adeno-associated virus (AAV) has been developed as a promising human gene therapy vector. Particularly, recombinant AAV vector (rAAV) achieves its transduction of host cells by crossing at least three physiological barriers including plasma membrane, endosomal membrane, and nuclear envelope (NE). So far, the AAV transduction mechanism has not been explored thoroughly at the single viral particle level. In this study, we employed high-speed super-resolution single-point edge-excitation sub-diffraction (SPEED) microscopy to map the events of single rAAV2 particles infecting live human cells with an unprecedented spatiotemporal resolution of 9-12 nm and 2-20 ms. Data reveal that rAAV2 particles are imported through nuclear pore complexes (NPCs) rather than nuclear membrane budding into the nucleus. Moreover, approximately 17% of the rAAV2 molecules starting from the cytoplasm successfully transverse the NPCs to reach the nucleoplasm, revealing that the NPCs act as a strict selective step for AAV delivery. This study lastly suggests a new pathway to improve AAV vectors for human gene therapy. PMID:26665132

  18. AIRE-induced apoptosis is associated with nuclear translocation of stress sensor protein GAPDH.

    PubMed

    Liiv, Ingrid; Haljasorg, Uku; Kisand, Kai; Maslovskaja, Julia; Laan, Martti; Peterson, Pärt

    2012-06-22

    AIRE (Autoimmune Regulator) has a central role in the transcriptional regulation of self-antigens in medullary thymic epithelial cells, which is necessary for negative selection of autoreactive T cells. Recent data have shown that AIRE can also induce apoptosis, which may be linked to cross-presentation of these self-antigens. Here we studied AIRE-induced apoptosis using AIRE over-expression in a thymic epithelial cell line as well as doxycycline-inducible HEK293 cells. We show that the HSR/CARD domain in AIRE together with a nuclear localization signal is sufficient to induce apoptosis. In the nuclei of AIRE-positive cells, we also found an increased accumulation of a glycolytic enzyme, glyceraldehyde-3-phosphate (GAPDH) reflecting cellular stress and apoptosis. Additionally, AIRE-induced apoptosis was inhibited with an anti-apoptotic agent deprenyl that blocks GAPDH nitrosylation and nuclear translocation. We propose that the AIRE-induced apoptosis pathway is associated with GAPDH nuclear translocation and induction of NO-induced cellular stress in AIRE-expressing cells.

  19. The Human Polycomb Group Complex Associates with Pericentromeric Heterochromatin to Form a Novel Nuclear Domain

    PubMed Central

    Saurin, Andrew J.; Shiels, Carol; Williamson, Jill; Satijn, David P.E.; Otte, Arie P.; Sheer, Denise; Freemont, Paul S.

    1998-01-01

    The Polycomb group (PcG) complex is a chromatin-associated multiprotein complex, involved in the stable repression of homeotic gene activity in Drosophila. Recently, a mammalian PcG complex has been identified with several PcG proteins implicated in the regulation of Hox gene expression. Although the mammalian PcG complex appears analogous to the complex in Drosophila, the molecular mechanisms and functions for the mammalian PcG complex remain unknown. Here we describe a detailed characterization of the human PcG complex in terms of cellular localization and chromosomal association. By using antibodies that specifically recognize three human PcG proteins— RING1, BMI1, and hPc2—we demonstrate in a number of human cell lines that the PcG complex forms a unique discrete nuclear structure that we term PcG bodies. PcG bodies are prominent novel nuclear structures with the larger PcG foci generally localized near the centromeres, as visualized with a kinetochore antibody marker. In both normal fetal and adult fibroblasts, PcG bodies are not randomly dispersed, but appear clustered into defined areas within the nucleus. We show in three different human cell lines that the PcG complex can tightly associate with large pericentromeric heterochromatin regions (1q12) on chromosome 1, and with related pericentromeric sequences on different chromosomes, providing evidence for a mammalian PcG–heterochromatin association. Furthermore, these heterochromatin-bound PcG complexes remain stably associated throughout mitosis, thereby allowing the potential inheritance of the PcG complex through successive cell divisions. We discuss these results in terms of the known function of the PcG complex as a transcriptional repression complex. PMID:9722603

  20. Anhydrobiosis-Associated Nuclear DNA Damage and Repair in the Sleeping Chironomid: Linkage with Radioresistance

    PubMed Central

    Vanyagina, Veronica; Malutina, Ludmila; Cornette, Richard; Sakashita, Tetsuya; Hamada, Nobuyuki; Kikawada, Takahiro; Kobayashi, Yasuhiko; Okuda, Takashi

    2010-01-01

    Anhydrobiotic chironomid larvae can withstand prolonged complete desiccation as well as other external stresses including ionizing radiation. To understand the cross-tolerance mechanism, we have analyzed the structural changes in the nuclear DNA using transmission electron microscopy and DNA comet assays in relation to anhydrobiosis and radiation. We found that dehydration causes alterations in chromatin structure and a severe fragmentation of nuclear DNA in the cells of the larvae despite successful anhydrobiosis. Furthermore, while the larvae had restored physiological activity within an hour following rehydration, nuclear DNA restoration typically took 72 to 96 h. The DNA fragmentation level and the recovery of DNA integrity in the rehydrated larvae after anhydrobiosis were similar to those of hydrated larvae irradiated with 70 Gy of high-linear energy transfer (LET) ions (4He). In contrast, low-LET radiation (gamma-rays) of the same dose caused less initial damage to the larvae, and DNA was completely repaired within within 24 h. The expression of genes encoding the DNA repair enzymes occurred upon entering anhydrobiosis and exposure to high- and low-LET radiations, indicative of DNA damage that includes double-strand breaks and their subsequent repair. The expression of antioxidant enzymes-coding genes was also elevated in the anhydrobiotic and the gamma-ray-irradiated larvae that probably functions to reduce the negative effect of reactive oxygen species upon exposure to these stresses. Indeed the mature antioxidant proteins accumulated in the dry larvae and the total activity of antioxidants increased by a 3–4 fold in association with anhydrobiosis. We conclude that one of the factors explaining the relationship between radioresistance and the ability to undergo anhydrobiosis in the sleeping chironomid could be an adaptation to desiccation-inflicted nuclear DNA damage. There were also similarities in the molecular response of the larvae to damage caused by

  1. A novel role for the nuclear membrane protein emerin in association of the centrosome to the outer nuclear membrane

    PubMed Central

    Salpingidou, Georgia; Smertenko, Andrei; Hausmanowa-Petrucewicz, Irena; Hussey, Patrick J.; Hutchison, Chris J.

    2007-01-01

    The type II inner nuclear membrane protein emerin is a component of the LINC complex that connects the nuclear lamina to the actin cytoskeleton. In emerin-null or -deficient human dermal fibroblasts we find that the centrosome is detached from the nucleus. Moreover, following siRNA knockdown of emerin in wild-type fibroblasts, the centrosome also becomes detached from the nucleus. We show that emerin interacts with tubulin, and that nocadozole-treated wild-type cells phenocopy the detached centrosome characteristic of emerin-null/deficient cells. We also find that a significant fraction of emerin is located at the outer nuclear membrane and peripheral ER, where it interacts directly with the centrosome. Our data provide the first evidence in mammalian cells as to the nature of the linkage of the centrosome, and therefore the tubulin cytoskeleton, with the outer nuclear membrane. PMID:17785515

  2. Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen induction by hypoxia and hypoxia-inducible factors.

    PubMed

    Veeranna, Ravindra P; Haque, Muzammel; Davis, David A; Yang, Min; Yarchoan, Robert

    2012-01-01

    Hypoxia and hypoxia-inducible factors (HIFs) play an important role in the Kaposi's sarcoma-associated herpesvirus (KSHV) life cycle. In particular, hypoxia can activate lytic replication of KSHV and specific lytic genes, including the replication and transcription activator (RTA), while KSHV infection in turn can increase the levels and activity of HIFs. In the present study, we show that hypoxia increases the levels of mRNAs encoding KSHV latency-associated nuclear antigen (LANA) in primary effusion lymphoma (PEL) cell lines and also increases the levels of LANA protein. Luciferase reporter assays in Hep3B cells revealed a moderate activation of the LANA promoter region by hypoxia as well as by cotransfection with degradation-resistant HIF-1α or HIF-2α expression plasmids. Computer analysis of a 1.2-kb sequence upstream of the LANA translational start site identified six potential hypoxia-responsive elements (HRE). Sequential deletion studies revealed that much of this activity was mediated by one of these HREs (HRE 4R) oriented in the 3' to 5' direction and located between the constitutive (LTc) and RTA-inducible (LTi) mRNA start sites. Site-directed mutation of this HRE substantially reduced the response to both HIF-1α and HIF-2α in a luciferase reporter assay. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrated binding of both HIF-1α and HIF-2α to this region. Also, HIF-1α was found to associate with RTA, and HIFs enhanced the activation of LTi by RTA. These results provide evidence that hypoxia and HIFs upregulate both latent and lytic KSHV replication and play a central role in the life cycle of this virus. PMID:22090111

  3. Nuclear entrapment and extracellular depletion of PCOLCE is associated with muscle degeneration in oculopharyngeal muscular dystrophy

    PubMed Central

    2013-01-01

    Background Muscle fibrosis characterizes degenerated muscles in muscular dystrophies and in late onset myopathies. Fibrotic muscles often exhibit thickening of the extracellular matrix (ECM). The molecular regulation of this process is not fully understood. In oculopharyngeal muscular dystrophy (OPMD), an expansion of an alanine tract at the N-terminus of poly(A)-binding protein nuclear 1 (PABPN1) causes muscle symptoms. OPMD patient muscle degeneration initiates after midlife, while at an earlier age carriers of alanine expansion mutant PABPN1 (expPABPN1) are clinically pre-symptomatic. OPMD is characterized by fibrosis in skeletal muscles but the causative molecular mechanisms are not fully understood. Methods We studied the molecular processes that are involved in OPMD pathology using cross-species mRNA expression profiles in muscles from patients and model systems. We identified significant dysregulation of the ECM functional group, among which the procollagen C-endopeptidase enhancer 1 gene (PCOLCE) was consistently down-regulated across species. We investigated PCOLCE subcellular localization in OPMD muscle samples and OPMD model systems to investigate any functional relevance of PCOLCE down-regulation in this disease. Results We found that muscle degeneration in OPMD is associated with PCOLCE down-regulation. In addition to its known presence at the ECM, we also found PCOLCE within the nucleus of muscle cells. PCOLCE sub-cellular localization changes during myoblast cell fusion and is disrupted in cells expressing mutant expPABPN1. Our results show that PCOLCE binds to soluble PABPN1 and co-localizes with aggregated PABPN1 with a preference for the mutant protein. In muscle biopsies from OPMD patients we find that extracellular PCOLCE is depleted with its concomitant enrichment within the nuclear compartment. Conclusions PCOLCE regulates collagen processing at the ECM. Depletion of extracellular PCOLCE is associated with the expression of expPABPN1 in OPMD

  4. Americium and plutonium association with magnesium hydroxide colloids in alkaline nuclear industry process environments

    NASA Astrophysics Data System (ADS)

    Maher, Zoe; Ivanov, Peter; O'Brien, Luke; Sims, Howard; Taylor, Robin J.; Heath, Sarah L.; Livens, Francis R.; Goddard, David; Kellet, Simon; Rand, Peter; Bryan, Nick D.

    2016-01-01

    The behaviours of Pu, Am and colloids in feed solutions to the Site Ion-exchange Effluent Plant (SIXEP) at the Sellafield nuclear reprocessing site in the U.K. have been studied. For both Pu and Am, fractions were found to be associated with material in the colloidal size range, with ˜50% of the Pu in the range 1-200 nm. The concentration of soluble Pu (<1 nm) was ˜1 nM, which is very similar to the solubility limit for Pu(V). The soluble Am concentration was of the order of 10-11 M, which was below the solubility limit of americium hydroxide. The size, morphology and elemental composition of the particulates and colloids in the feed solutions were investigated. Magnesium is homogeneously distributed throughout the particles, whereas U, Si, Fe, and Ca were present in localised areas only. Amongst some heterogeneous material, particles were identified that were consistent with hydrotalcite. The distribution of 241Am(III) on brucite (magnesium hydroxide) colloids of different sizes was studied under alkaline conditions representative of nuclear fuel storage pond and effluent feed solution conditions. The morphology of the brucite particles in the bulk material observed by ESEM was predominantly hexagonal, while that of the carbonated brucite consisted of hexagonal species mixed with platelets. The association of 241Am(III) with the brucite colloids was studied by ultrafiltration coupled with gamma ray-spectrometry. For carbonate concentrations up to 10-3 M, the 241Am(III) was mainly associated with larger colloids (>300 kDa), and there was a shift from the smaller size fractions to the larger over a period of 6 months. At higher carbonate concentrations (10-2 M), the Am was predominantly detected in the true solution fraction (<3 kDa) and in smaller size colloidal fractions, in the range 3-100 kDa.

  5. Changes in mitochondrial DNA alter expression of nuclear encoded genes associated with tumorigenesis

    SciTech Connect

    Jandova, Jana; Janda, Jaroslav; Sligh, James E

    2012-10-15

    We previously reported the presence of a mtDNA mutation hotspot in UV-induced premalignant and malignant skin tumors in hairless mice. We have modeled this change (9821insA) in murine cybrid cells and demonstrated that this alteration in mtDNA associated with mtBALB haplotype can alter the biochemical characteristics of cybrids and subsequently can contribute to significant changes in their behavioral capabilities. This study shows that changes in mtDNA can produce differences in expression levels of specific nuclear-encoded genes, which are capable of triggering the phenotypes such as seen in malignant cells. From a potential list of differentially expressed genes discovered by microarray analysis, we selected MMP-9 and Col1a1 for further studies. Real-time PCR confirmed up-regulation of MMP-9 and down-regulation of Col1a1 in cybrids harboring the mtDNA associated with the skin tumors. These cybrids also showed significantly increased migration and invasion abilities compared to wild type. The non-specific MMP inhibitor, GM6001, was able to inhibit migratory and invasive abilities of the 9821insA cybrids confirming a critical role of MMPs in cellular motility. Nuclear factor-{kappa}B (NF-{kappa}B) is a key transcription factor for production of MMPs. An inhibitor of NF-{kappa}B activation, Bay 11-7082, was able to inhibit the expression of MMP-9 and ultimately decrease migration and invasion of mutant cybrids containing 9821insA. These studies confirm a role of NF-{kappa}B in the regulation of MMP-9 expression and through this regulation modulates the migratory and invasive capabilities of cybrids with mutant mtDNA. Enhanced migration and invasion abilities caused by up-regulated MMP-9 may contribute to the tumorigenic phenotypic characteristics of mutant cybrids. -- Highlights: Black-Right-Pointing-Pointer Cybrids are useful models to study the role of mtDNA changes in cancer development. Black-Right-Pointing-Pointer mtDNA changes affect the expression of nuclear

  6. Yes-Associated Protein (YAP) Promotes the Nuclear Import of p73

    NASA Astrophysics Data System (ADS)

    Zhang, Heng; Wu, Shengnan

    2011-01-01

    p73 has been identified as a structural and functional homolog of the tumor suppressor p53. However, mechanisms that regulate the localization of p73 have not been fully clarified. The Yes-associated protein (YAP) is a transcriptional coactivator. As a transcriptional coactivator, YAP needs to bind transcription factors to stimulate gene expression. p73 is a reported YAP target transcription factors and YAP has been shown to positively regulate p73 in promoting apoptosis. Previous studies show that p73 interacts with YAP through its PPPY motif, and increases p73 transactivation of apoptotic genes. In this study, we focused on YAP's regulation of the localization of p73. After transient transfection into Rat pheochromocytoma (PC12) cells and Human embryonic kidney 293T cells with GFP-YAP and/or YFP-p73, and incubated for 24 hours expression. p73 was fused to YFP to allow the examination of its subcellular localization. When expressed alone, YFP-p73 was distributed throughout the cell. When coexpressed with YAP, nuclear accumulation of YFP-p73 became evident. We quantitated the effect of YAP on the redistribution of YFP-p73 by counting cells with nuclear-only YFP signal. We found that YAP can influence the subcellular distribution of p73. Altogether, coexpression with YAP affected the subcellular distribution of the p73 protein. Our studies attribute a central role to YAP in regulating p73 accumulation and YAP, at least in part, might promote the nuclear import of p73.

  7. David Kasner, MD, and the Road to Pars Plana Vitrectomy.

    PubMed

    Blodi, Christopher F

    2016-01-01

    David Kasner, MD (1927-2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966-1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner's work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

  8. David Kasner, MD, and the Road to Pars Plana Vitrectomy

    PubMed Central

    Blodi, Christopher F.

    2016-01-01

    David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

  9. David Kasner, MD, and the Road to Pars Plana Vitrectomy

    PubMed Central

    Blodi, Christopher F.

    2016-01-01

    David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy.

  10. Identifying Protein-Protein Associations at the Nuclear Envelope with BioID.

    PubMed

    Kim, Dae In; Jensen, Samuel C; Roux, Kyle J

    2016-01-01

    The nuclear envelope (NE) is a critical cellular structure whose constituents and roles in a myriad of cellular processes seem ever expanding. To determine the underlying mechanisms by which the NE constituents participate in various cellular events, it is necessary to understand the nature of their protein-protein associations. BioID (proximity-dependent biotin identification) is a recently established method to generate a history of protein-protein associations as they occur over time in living cells. BioID is based on fusion of a bait protein to a promiscuous biotin ligase. Expression of the BioID fusion protein in a relevant cellular environment enables biotinylation of vicinal and interacting proteins of the bait protein, permitting isolation and identification by conventional biotin-affinity capture and mass-spec analysis. In this way, BioID provides unique capabilities to identify protein-protein associations at the NE. In this chapter we provide a detailed protocol for the application of BioID to the study of NE proteins.

  11. Changes in mitochondrial DNA alter expression of nuclear encoded genes associated with tumorigenesis.

    PubMed

    Jandova, Jana; Janda, Jaroslav; Sligh, James E

    2012-10-15

    We previously reported the presence of a mtDNA mutation hotspot in UV-induced premalignant and malignant skin tumors in hairless mice. We have modeled this change (9821insA) in murine cybrid cells and demonstrated that this alteration in mtDNA associated with mtBALB haplotype can alter the biochemical characteristics of cybrids and subsequently can contribute to significant changes in their behavioral capabilities. This study shows that changes in mtDNA can produce differences in expression levels of specific nuclear-encoded genes, which are capable of triggering the phenotypes such as seen in malignant cells. From a potential list of differentially expressed genes discovered by microarray analysis, we selected MMP-9 and Col1a1 for further studies. Real-time PCR confirmed up-regulation of MMP-9 and down-regulation of Col1a1 in cybrids harboring the mtDNA associated with the skin tumors. These cybrids also showed significantly increased migration and invasion abilities compared to wild type. The non-specific MMP inhibitor, GM6001, was able to inhibit migratory and invasive abilities of the 9821insA cybrids confirming a critical role of MMPs in cellular motility. Nuclear factor-κB (NF-κB) is a key transcription factor for production of MMPs. An inhibitor of NF-κB activation, Bay 11-7082, was able to inhibit the expression of MMP-9 and ultimately decrease migration and invasion of mutant cybrids containing 9821insA. These studies confirm a role of NF-κB in the regulation of MMP-9 expression and through this regulation modulates the migratory and invasive capabilities of cybrids with mutant mtDNA. Enhanced migration and invasion abilities caused by up-regulated MMP-9 may contribute to the tumorigenic phenotypic characteristics of mutant cybrids.

  12. Changes in mitochondrial DNA alter expression of nuclear encoded genes associated with tumorigenesis

    PubMed Central

    Jandova, Jana; Janda, Jaroslav; Sligh, James E

    2012-01-01

    We previously reported the presence of a mtDNA mutation hotspot in UV-induced premalignant and malignant skin tumors in hairless mice. We have modeled this change (9821insA) in murine cybrid cells and demonstrated that this alteration in mtDNA associated with mtBALB haplotype can alter the biochemical characteristics of cybrids and subsequently can contribute to significant changes in their behavioral capabilities. This study shows that changes in mtDNA can produce differences in expression levels of specific nuclear-encoded genes, which are capable of triggering the phenotypes such as seen in malignant cells. From a potential list of differentially expressed genes discovered by microarray analysis, we selected MMP-9 and Col1a1 for further studies. Real-time PCR confirmed up-regulation of MMP-9 and down-regulation of Col1a1 in cybrids harboring the mtDNA associated with the skin tumors. These cybrids also showed significantly increased migration and invasion abilities compared to wild type. The non-specific MMP inhibitor, GM6001, was able to inhibit migratory and invasive abilities of the 9821insA cybrids confirming a critical role of MMPs in cellular motility. Nuclear factor-κB (NF-κB) is a key transcription factor for production of MMPs. An inhibitor of NF-κB activation, Bay11-7082, was able to inhibit the expression of MMP-9 and ultimately decrease migration and invasion of mutant cybrids containing 9821insA. These studies confirm a role of NF-κB in the regulation of MMP-9 expression and through this regulation modulates the migratory and invasive capabilities of cybrids with mutant mtDNA. Enhanced migration and invasion abilities caused by up-regulated MMP-9 may contribute to the tumorigenic phenotypic characteristics of mutant cybrids. PMID:22705584

  13. Hepatitis C-associated liver carcinogenesis: Role of PML nuclear bodies

    PubMed Central

    Herzer, Kerstin; Gerken, Guido; Hofmann, Thomas G

    2014-01-01

    Successful escape from immune response characterises chronic hepatitis C virus (HCV) infection, which results in persistence of infection in about 80% of the patients. The deleterious consequences are cirrhosis and hepatocellular carcinoma. HCV accounts the most frequent cause for hepatocellular carcinoma (HCC) and liver transplantation (LT) in the western world. The underlying molecular mechanisms how HCV promotes tumor development are largely unknown. There is some in vitro and in vivo evidence that HCV interferes with the tumor suppressor PML and may thereby importantly contribute to the HCV-associated pathogenesis with respect to the development of HCC. The tumor suppressor protein “promyelocytic leukemia” (PML) has been implicated in the regulation of important cellular processes like differentiation and apoptosis. In cancer biology, PML and its associated nuclear bodies (NBs) have initially attracted intense interest due to its role in the pathogenesis of acute promyelocytic leukemia (APL). More recently, loss of PML has been implicated in human cancers of various histologic origins. Moreover, number and intensity of PML-NBs increase in response to interferons (IFNs) and there is evidence that PML-NBs may represent preferential targets in viral infections. Thus, PML could not only play a role in the mechanisms of the antiviral action of IFNs but may also be involved in a direct oncogenic effect of the HCV on hepatocytes. This review aims to summarise current knowledge about HCV-related liver carcinogenesis and to discuss a potential role of the nuclear body protein PML for this this hard-to-treat cancer. PMID:25253937

  14. Midwest Nuclear Training Association Annual Nuclear Instructors' Workshop (4th, Columbus, Ohio, October 16-18, 1989).

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Center on Education and Training for Employment.

    This document reports the proceedings of a national workshop designed to provide nuclear trainers from the electric power industry with an opportunity to expand and improve their knowledge and skills in the development and implementation of effective training programs. The following papers are included: "Developing Positive Worker Behaviors:…

  15. Environmental problems associated with decommissioning the Chernobyl Nuclear Power Plant Cooling Pond.

    PubMed

    Oskolkov, B Ya; Bondarkov, M D; Gaschak, S P; Maksymenko, A M; Maksymenko, V M; Martynenko, V I; Farfán, E B; Jannik, G T; Marra, J C

    2010-11-01

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities associated with residual radioactive contamination of their territories is an imperative issue. Significant problems may result from decommissioning of cooling ponds with residual radioactive contamination. The Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond is one of the largest self-contained water reservoirs in the Chernobyl region and Ukrainian and Belorussian Polesye region. The 1986 ChNPP Reactor Unit Number Four significantly contaminated the ChNPP Cooling Pond. The total radionuclide inventory in the ChNPP Cooling Pond bottom deposits are as follows: ¹³⁷Cs: 16.28 ± 2.59 TBq; ⁹⁰Sr: 2.4 ± 0.48 TBq; and ²³⁹+²⁴⁰Pu: 0.00518 ± 0.00148 TBq. The ChNPP Cooling Pond is inhabited by over 500 algae species and subspecies, over 200 invertebrate species, and 36 fish species. The total mass of the living organisms in the ChNPP Cooling Pond is estimated to range from about 60,000 to 100,000 tons. The territory adjacent to the ChNPP Cooling Pond attracts many birds and mammals (178 bird species and 47 mammal species were recorded in the Chernobyl Exclusion Zone). This article describes several options for the ChNPP Cooling Pond decommissioning and environmental problems associated with its decommissioning. The article also provides assessments of the existing and potential exposure doses for the shoreline biota. For the 2008 conditions, the estimated total dose rate values were 11.4 40 μGy h⁻¹ for amphibians, 6.3 μGy h⁻¹ for birds, 15.1 μGy h⁻¹ for mammals, and 10.3 μGy h⁻¹ for reptiles, with the recommended maximum dose rate being equal to 40 μGy h⁻¹. However, drying the ChNPP Cooling Pond may increase the exposure doses to 94.5 μGy h⁻¹ for amphibians, 95.2 μGy h⁻¹ for birds, 284.0 μGy h⁻¹ for mammals, and 847.0 μGy h⁻¹ for reptiles. All of these anticipated dose rates exceed the recommended values.

  16. Environmental problems associated with decommissioning the Chernobyl Nuclear Power Plant Cooling Pond.

    PubMed

    Oskolkov, B Ya; Bondarkov, M D; Gaschak, S P; Maksymenko, A M; Maksymenko, V M; Martynenko, V I; Farfán, E B; Jannik, G T; Marra, J C

    2010-11-01

    Decommissioning of nuclear power plants and other nuclear fuel cycle facilities associated with residual radioactive contamination of their territories is an imperative issue. Significant problems may result from decommissioning of cooling ponds with residual radioactive contamination. The Chernobyl Nuclear Power Plant (ChNPP) Cooling Pond is one of the largest self-contained water reservoirs in the Chernobyl region and Ukrainian and Belorussian Polesye region. The 1986 ChNPP Reactor Unit Number Four significantly contaminated the ChNPP Cooling Pond. The total radionuclide inventory in the ChNPP Cooling Pond bottom deposits are as follows: ¹³⁷Cs: 16.28 ± 2.59 TBq; ⁹⁰Sr: 2.4 ± 0.48 TBq; and ²³⁹+²⁴⁰Pu: 0.00518 ± 0.00148 TBq. The ChNPP Cooling Pond is inhabited by over 500 algae species and subspecies, over 200 invertebrate species, and 36 fish species. The total mass of the living organisms in the ChNPP Cooling Pond is estimated to range from about 60,000 to 100,000 tons. The territory adjacent to the ChNPP Cooling Pond attracts many birds and mammals (178 bird species and 47 mammal species were recorded in the Chernobyl Exclusion Zone). This article describes several options for the ChNPP Cooling Pond decommissioning and environmental problems associated with its decommissioning. The article also provides assessments of the existing and potential exposure doses for the shoreline biota. For the 2008 conditions, the estimated total dose rate values were 11.4 40 μGy h⁻¹ for amphibians, 6.3 μGy h⁻¹ for birds, 15.1 μGy h⁻¹ for mammals, and 10.3 μGy h⁻¹ for reptiles, with the recommended maximum dose rate being equal to 40 μGy h⁻¹. However, drying the ChNPP Cooling Pond may increase the exposure doses to 94.5 μGy h⁻¹ for amphibians, 95.2 μGy h⁻¹ for birds, 284.0 μGy h⁻¹ for mammals, and 847.0 μGy h⁻¹ for reptiles. All of these anticipated dose rates exceed the recommended values. PMID:20938234

  17. Idealism and romantic patriotism for science - an interview with José Francisco David-Ferreira.

    PubMed

    David-Ferreira, José Francisco

    2009-01-01

    Jose Francisco David-Ferreira is one of the most influential Professors of Cell and Developmental Biology in Portugal. David-Ferreira pioneered the use of electron microscopy in cell biology and experimental embryology. He also paved the way for successive generations of biologists who cross-fertilized the national scientific community. As we discuss briefly below, David-Ferreira is above all a Pedagogue and an Institution builder. PMID:19247950

  18. Attitudes of Mississippi college students toward David Duke before and after seeing the film Who is David Duke?

    PubMed

    Eisenman, R; Girdner, E J; Burroughs, R G; Routman, M

    1993-01-01

    The attitudes of 211 students at a university in Mississippi were investigated both before and after seeing the Public Broadcasting Film Who Is David Duke? The film provided evidence of Duke's current racism, anti-Semitism, and pro-Nazi leanings. In a previous study with university students in Louisiana, the majority did not change their attitudes after watching the film (Eisenman, 1993). However, in the present study, students' attitudes showed change in an anti-Duke direction. The findings are discussed and reasons given for the differences between the two samples, and for the popularity of Duke, a former leader of the Ku Klux Klan.

  19. Attitudes of Mississippi college students toward David Duke before and after seeing the film Who is David Duke?

    PubMed

    Eisenman, R; Girdner, E J; Burroughs, R G; Routman, M

    1993-01-01

    The attitudes of 211 students at a university in Mississippi were investigated both before and after seeing the Public Broadcasting Film Who Is David Duke? The film provided evidence of Duke's current racism, anti-Semitism, and pro-Nazi leanings. In a previous study with university students in Louisiana, the majority did not change their attitudes after watching the film (Eisenman, 1993). However, in the present study, students' attitudes showed change in an anti-Duke direction. The findings are discussed and reasons given for the differences between the two samples, and for the popularity of Duke, a former leader of the Ku Klux Klan. PMID:8237541

  20. The development of next-generation sequencing assays for the mitochondrial genome and 108 nuclear genes associated with mitochondrial disorders.

    PubMed

    Dames, Shale; Chou, Lan-Szu; Xiao, Ye; Wayman, Tyler; Stocks, Jennifer; Singleton, Marc; Eilbeck, Karen; Mao, Rong

    2013-07-01

    Sanger sequencing of multigenic disorders can be technically challenging, time consuming, and prohibitively expensive. High-throughput next-generation sequencing (NGS) can provide a cost-effective method for sequencing targeted genes associated with multigenic disorders. We have developed a NGS clinical targeted gene assay for the mitochondrial genome and for 108 selected nuclear genes associated with mitochondrial disorders. Mitochondrial disorders have a reported incidence of 1 in 5000 live births, encompass a broad range of phenotypes, and are attributed to mutations in the mitochondrial and nuclear genomes. Approximately 20% of mitochondrial disorders result from mutations in mtDNA, with the remaining 80% found in nuclear genes that affect mtDNA levels or mitochondrion protein assembly. In our NGS approach, the 16,569-bp mtDNA is enriched by long-range PCR and the 108 nuclear genes (which represent 1301 amplicons and 680 kb) are enriched by RainDance emulsion PCR. Sequencing is performed on Illumina HiSeq 2000 or MiSeq platforms, and bioinformatics analysis is performed using commercial and in-house developed bioinformatics pipelines. A total of 16 validation and 13 clinical samples were examined. All previously reported variants associated with mitochondrial disorders were found in validation samples, and 5 of the 13 clinical samples were found to have mutations associated with mitochondrial disorders in either the mitochondrial genome or the 108 nuclear genes. All variants were confirmed by Sanger sequencing.

  1. Associations between Disaster Exposures, Peritraumatic Distress, and Posttraumatic Stress Responses in Fukushima Nuclear Plant Workers following the 2011 Nuclear Accident: The Fukushima NEWS Project Study

    PubMed Central

    Shigemura, Jun; Tanigawa, Takeshi; Nishi, Daisuke; Matsuoka, Yutaka; Nomura, Soichiro; Yoshino, Aihide

    2014-01-01

    Background The 2011 Fukushima Daiichi Nuclear Power Plant accident was the worst nuclear disaster since Chernobyl. The nearby Daini plant also experienced substantial damage but remained intact. Workers for the both plants experienced multiple stressors as disaster victims and workers, as well as the criticism from the public due to their company's post-disaster management. Little is known about the psychological pathway mechanism from nuclear disaster exposures, distress during and immediately after the event (peritraumatic distress; PD), to posttraumatic stress responses (PTSR). Methods A self-report questionnaire was administered to 1,411 plant employees (Daiichi, n = 831; Daini, n = 580) 2–3 months post-disaster (total response rate: 80.2%). The socio-demographic characteristics and disaster-related experiences were assessed as independent variables. PD and PTSR were measured by the Japanese versions of Peritraumatic Distress Inventory and the Impact of Event Scale-Revised, respectively. The analysis was conducted separately for the two groups. Bivariate regression analyses were performed to assess the relationships between independent variables, PD, and PTSR. Significant variables were subsequently entered in the multiple regression analyses to explore the pathway mechanism for development of PTSR. Results For both groups, PTSR highly associated with PD (Daiichi: adjusted β, 0.66; p<0.001; vs. Daini: adjusted β, 0.67; p<0.001). PTSR also associated with discrimination/slurs experience (Daiichi: 0.11; p<0.001; vs. Daini, 0.09; p = 0.005) and presence of preexisting illness(es) (Daiichi: 0.07; p = 0.005; vs. Daini: 0.15; p<.0001). Other disaster-related variables were likely to be associated with PD than PTSR. Conclusion Among the Fukushima nuclear plant workers, disaster exposures associated with PD. PTSR was highly affected by PD along with discrimination/slurs experience. PMID:24586278

  2. Nuclear factor, erythroid 2-like 2-associated molecular signature predicts lung cancer survival

    PubMed Central

    Qian, Zhongqing; Zhou, Tong; Gurguis, Christopher I.; Xu, Xiaoyan; Wen, Qing; Lv, Jingzhu; Fang, Fang; Hecker, Louise; Cress, Anne E.; Natarajan, Viswanathan; Jacobson, Jeffrey R.; Zhang, Donna D.; Garcia, Joe G. N.; Wang, Ting

    2015-01-01

    Nuclear factor, erythroid 2-like 2 (NFE2L2), a transcription factor also known as NF-E2-related factor 2 (Nrf2), is a key cytoprotective gene that regulates critical antioxidant and stress-responsive genes. Nrf2 has been demonstrated to be a promising therapeutic target and useful biomarker in malignant disease. We hypothesized that NFE2L2-mediated gene expression would reflect cancer severity and progression. We conducted a meta-analysis of microarray data for 240 NFE2L2-mediated genes that were enriched in tumor tissues. We then developed a risk scoring system based on NFE2L2 gene expression profiling and designated 50 tumor-associated genes as the NFE2L2-associated molecular signature (NAMS). We tested the relationship between this gene expression signature and both recurrence-free survival and overall survival in lung cancer patients. We find that NAMS predicts clinical outcome in the training cohort and in 12 out of 20 validation cohorts. Cox proportional hazard regressions indicate that NAMS is a robust prognostic gene signature, independent of other clinical and pathological factors including patient age, gender, smoking, gene alteration, MYC level, and cancer stage. NAMS is an excellent predictor of recurrence-free survival and overall survival in human lung cancer. This gene signature represents a promising prognostic biomarker in human lung cancer. PMID:26596768

  3. An association between RBMX, a heterogeneous nuclear ribonucleoprotein, and ARTS-1 regulates extracellular TNFR1 release

    SciTech Connect

    Adamik, Barbara; Islam, Aminul; Rouhani, Farshid N.; Hawari, Feras I.; Zhang Jing; Levine, Stewart J.

    2008-07-04

    The type I, 55-kDa tumor necrosis factor receptor (TNFR1) is released to the extracellular space by two mechanisms, the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains. Both pathways appear to be regulated by an interaction between TNFR1 and ARTS-1 (aminopeptidase regulator of TNFR1 shedding). Here, we sought to identify ARTS-1-interacting proteins that modulate TNFR1 release. Co-immunoprecipitation identified an association between ARTS-1 and RBMX (RNA-binding motif gene, X chromosome), a 43-kDa heterogeneous nuclear ribonucleoprotein. RNA interference attenuated RBMX expression, which reduced both the constitutive release of TNFR1 exosome-like vesicles and the IL-1{beta}-mediated inducible proteolytic cleavage of soluble TNFR1 ectodomains. Reciprocally, over-expression of RBMX increased TNFR1 exosome-like vesicle release and the IL-1{beta}-mediated inducible shedding of TNFR1 ectodomains. This identifies RBMX as an ARTS-1-associated protein that regulates both the constitutive release of TNFR1 exosome-like vesicles and the inducible proteolytic cleavage of TNFR1 ectodomains.

  4. A case of anti-nuclear matrix protein 2 antibody positive myopathy associated with lung cancer.

    PubMed

    Ohta, Shin; Unoda, Ki-Ichi; Nakajima, Hideto; Ikeda, Soichiro; Hamaguchi, Yasuhito; Kimura, Fumiharu

    2016-08-31

    Myositis-specific autoantibodies (MSAs) are associated with myositis. Anti-nuclear matrix protein 2 (NXP-2) antibody was recently identified as a major MSA and was observed mostly in juvenile dermatomyositis. We report the case of a 44-year-old man who presented with myopathy with anti-NXP-2 antibody and large cell carcinoma of the lung. He was hospitalized because of myalgia and edema of limbs. Neurological examination revealed mild proximal-dominant weakness in all four extremities, and laboratory studies showed elevated creatine kinase level (6,432 IU/l). Needle electromyography showed myogenic patterns. MRI of the lower limbs demonstrated inflammatory lesions in the thighs. Biopsied specimen from the left quadriceps femoris muscle showed mild mononuclear inflammatory infiltrate surrounding muscle fibres but no fiber necrosis. He was diagnosed with myopathy based on neurological examinations and clinical symptoms. His chest X-ray and CT showed tumor shadow on the right upper lung field, but CT didn't indicate the findings of interstitial lung disease. This was surgically removed, and a histological diagnosis of non-small cell lung cancer was suspected. He was also treated with definitive chemoradiotherapy before and after operation. His symptoms of myopathy promptly remitted with the preoperative chemotherapy. His serum analysis was positive for the anti-NXP-2. Further investigation and experience of MSAs are necessary to evaluate the therapeutic strategy against cancer-associated myopathy/myositis. PMID:27477574

  5. Considerations Associated with Reactor Technology Selection for the Next Generation Nuclear Plant Project

    SciTech Connect

    L.E. Demick

    2010-09-01

    At the inception of the Next Generation Nuclear Plant Project and during predecessor activities, alternative reactor technologies have been evaluated to determine the technology that best fulfills the functional and performance requirements of the targeted energy applications and market. Unlike the case of electric power generation where the reactor performance is primarily expressed in terms of economics, the targeted energy applications involve industrial applications that have specific needs in terms of acceptable heat transport fluids and the associated thermodynamic conditions. Hence, to be of interest to these industrial energy applications, the alternative reactor technologies are weighed in terms of the reactor coolant/heat transport fluid, achievable reactor outlet temperature, and practicality of operations to achieve the very high reliability demands associated with the petrochemical, petroleum, metals and related industries. These evaluations have concluded that the high temperature gas-cooled reactor (HTGR) can uniquely provide the required ranges of energy needs for these target applications, do so with promising economics, and can be commercialized with reasonable development risk in the time frames of current industry interest – i.e., within the next 10-15 years.

  6. David Hartley's views on Madness: With an introduction by GE Berrios.

    PubMed

    Berrios, G E

    2015-03-01

    The psychiatric aspects of David Hartley's writings have received less attention than the rest of his work. This Classic Text deals with Section VI of his Observations on Man …, namely, the 'Imperfections of the rational Faculty'. Hartley defines madness as an imperfection of reason that can be temporary or enduring. He makes use of his model of mental functioning to differentiate between eight clinical categories of madness, each representing a different pattern of vibrations of the nerves. Hartley developed this model based on Newton's theory of vibrations and, to explain the complexity of mental acts and entities, he combined it with his own version of the mechanism of Association of Ideas borrowed from John Locke. Much work needs to be done to identify the provenance of Hartley's nosology and nosography.

  7. Fuel-Cycle and Nuclear Material Disposition Issues Associated with High-Temperature Gas Reactors

    SciTech Connect

    Shropshire, D.E.; Herring, J.S.

    2004-10-03

    The objective of this paper is to facilitate a better understanding of the fuel-cycle and nuclear material disposition issues associated with high-temperature gas reactors (HTGRs). This paper reviews the nuclear fuel cycles supporting early and present day gas reactors, and identifies challenges for the advanced fuel cycles and waste management systems supporting the next generation of HTGRs, including the Very High Temperature Reactor, which is under development in the Generation IV Program. The earliest gas-cooled reactors were the carbon dioxide (CO2)-cooled reactors. Historical experience is available from over 1,000 reactor-years of operation from 52 electricity-generating, CO2-cooled reactor plants that were placed in operation worldwide. Following the CO2 reactor development, seven HTGR plants were built and operated. The HTGR came about from the combination of helium coolant and graphite moderator. Helium was used instead of air or CO2 as the coolant. The helium gas has a significant technical base due to the experience gained in the United States from the 40-MWe Peach Bottom and 330-MWe Fort St. Vrain reactors designed by General Atomics. Germany also built and operated the 15-MWe Arbeitsgemeinschaft Versuchsreaktor (AVR) and the 300-MWe Thorium High-Temperature Reactor (THTR) power plants. The AVR, THTR, Peach Bottom and Fort St. Vrain all used fuel containing thorium in various forms (i.e., carbides, oxides, thorium particles) and mixtures with highly enriched uranium. The operational experience gained from these early gas reactors can be applied to the next generation of nuclear power systems. HTGR systems are being developed in South Africa, China, Japan, the United States, and Russia. Elements of the HTGR system evaluated included fuel demands on uranium ore mining and milling, conversion, enrichment services, and fuel fabrication; fuel management in-core; spent fuel characteristics affecting fuel recycling and refabrication, fuel handling, interim

  8. Nuclear localization of Toll-like receptor 5 in Barrett's esophagus and esophageal adenocarcinoma is associated with metastatic behavior.

    PubMed

    Helminen, Olli; Huhta, Heikki; Leppänen, Joni; Kauppila, Joonas H; Takala, Heikki; Lehenkari, Petri P; Saarnio, Juha; Karttunen, Tuomo J

    2016-10-01

    Toll-like receptor 5 (TLR5) recognizes bacterial flagellin. Increased cytoplasmic and nuclear expression of some TLRs has been previously reported in dysplasia in Barrett's esophagus and various malignant lesions in association with survival and metastasis. We assessed nuclear expression of TLR5 in Barrett's esophagus and esophageal adenocarcinoma (n = 94) by immunohistochemistry and immunofluorescent staining. Nuclear expression was observed in the majority of studied lesions with high variation in the proportion of positive nuclei. Expression in lymph node metastases was significantly higher than in esophageal lesions (p < 0.05), except for intestinal metaplasia and low-grade dysplasia. Furthermore, nuclear expression of TLR5 was associated with the presence of lymph node metastases (p = 0.033). In conclusion, we report nuclear TLR5 expression in Barrett's esophagus and adenocarcinoma. Abundance of positive nuclei in association with lymph node metastases suggests that TLR5 is involved in the pathogenesis and dissemination of esophageal adenocarcinoma through as-yet-uncharacterized mechanisms.

  9. The Nuclear Receptor, Nor-1, Induces the Physiological Responses Associated With Exercise.

    PubMed

    Goode, Joel M; Pearen, Michael A; Tuong, Zewen K; Wang, Shu-Ching M; Oh, Tae Gyu; Shao, Emily X; Muscat, George E O

    2016-06-01

    Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling response to physical activity can ameliorate/prevent diseases associated with poor diet and lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives muscle reprogramming, improves exercise endurance, and oxidative metabolism. The current manuscript investigates the association between exercise, Nor-1 expression and the role of Nor-1 in adaptive remodeling. We demonstrate that Nor-1 expression is induced by exercise and is dependent on calcium/calcineurin signaling (in vitro and in vivo). Analysis of fatigue-resistant transgenic mice that express Nor-1 in skeletal muscle revealed increased hypertrophy and vascularization of muscle tissue. Moreover, we demonstrate that transgenic Nor-1 expression is associated with increased intracellular recycling, ie, autophagy, involving 1) increased expression of light chain 3A or LC3A-II, autophagy protein 5, and autophagy protein 12 in quadriceps femoris muscle extracts from Tg-Nor-1 (relative to Wild-type (WT) littermates); 2) decreased p62 expression indicative of increased autophagolysosome assembly; and 3) decreased mammalian target of rapamycin complex 1 activity. Transfection of LC3A-GFP-RFP chimeric plasmid demonstrated that autophagolysosome formation was significantly increased by Nor-1 expression. Furthermore, we demonstrated a single bout of exercise induced LC3A-II expression in skeletal muscle from C57BL/6 WT mice. This study, when combined with our previous studies, demonstrates that Nor-1 expression drives multiple physiological changes/pathways that are critical to the beneficial responses of muscle to exercise and provides insights into potential pharmacological manipulation of muscle reprogramming for the treatment of lifestyle induced chronic diseases. PMID:27144290

  10. STS-86 Mission Specialist David Wolf suits up

    NASA Technical Reports Server (NTRS)

    1997-01-01

    STS-86 Mission Specialist David A. Wolf gets assistance from a suit technician while donning his orange launch and entry suit in the Operations and Checkout Building. This will be Wolfs second flight. He and the six other crew members will depart shortly for Launch Pad 39A, where the Space Shuttle Atlantis awaits liftoff on a 10-day mission slated to be the seventh docking of the Space Shuttle with the Russian Space Station Mir. Wolf will transfer to the Mir 24 crew, replacing U.S. astronaut C. Michael Foale, who will return to Earth aboard Atlantis with the rest of the STS-86 crew. Wolf is expected to live and work aboard the Russian space station for about four months.

  11. David Ayman, MD: an early investigator of clinical hypertension.

    PubMed

    Materson, Barry J; Leclercq, Baudouin

    2005-04-01

    Dr. David Ayman (1901-1986) was an astute clinician and observer who challenged medical dogma by performing placebo-controlled studies and by meticulous measurement of blood pressure under standardized conditions. He demonstrated that almost all drugs reported to have an antihypertensive effect in the early 20th century had achieved nothing more than placebo response. He noted the marked variability of blood pressure and devised methods to reduce that variability. These observations led to his publications concerning what is now known as "white coat" or office hypertension. He determined blood pressure personally in 1524 members of 277 families over three generations and made observations on the hereditary nature of hypertension that countered the single-gene thinking of the day. His work is proof that clinical inquisitiveness, hard work, and the courage to challenge conventional wisdom can result in significant contributions to medicine and science. PMID:15860961

  12. Astronaut David Brown talks with team members from South Carolina

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown looks over the robot named 'L'il Max' with members of the team The Bot Kickers! from Northwestern High School, Rock Hill, S.C. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition being held March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co- sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  13. Astronaut David Brown talks to FIRST team members

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown talks with FIRST team members, Baxter Bomb Squad, from Mountain Home High School, Mountain Home, Ariz., during the FIRST competition. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  14. Astronaut David Brown poses with ComBBat team

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown poses with members of the team known as ComBBat, representing Central Florida's Astronaut and Titusville high schools. ComBBat was teamed with Boeing at KSC and Brevard Community College. Students from all over the country are at the KSC Visitor Complex for the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition being held March 9-11 in the Rocket Garden. Teams of high school students are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  15. The Greening of the David L. Lawrence Pittsburgh Convention Center

    NASA Astrophysics Data System (ADS)

    Leahy, Mark

    2009-03-01

    The David L. Lawrence Convention Center is the largest Gold LEED NC (new construction) certified convention center in the USA and the first of its kind in the world. The designation has been awarded by the United States Green Building Council through its Leadership in Energy and Environmental Design (LEED) Green Building Rating System. In this talk we discuss the unique green properties of this 1.5 million square foot Convention Center including the design and use of daylight, natural ventilation and other sustainable design and practices. No other building the size of the Convention Center (1.5 million square feet), uses natural ventilation or can illuminate an exhibition hall entirely through its windows and skylights. Approximately 75% of the convention center's exhibition space is lit by natural daylight. The use of natural ventilation and extensive day lighting is designed to reduce energy consumption by nearly 35% compared to traditional ventilated and lit buildings of a similar size.

  16. David Duke, running for governor, proposes tattooing people with HIV.

    PubMed

    1995-05-19

    Former Ku Klux Klan leader, David Duke, planning a second run for governor of Louisiana, said he would curb the AIDS epidemic by tattooing people who are infected with HIV. His suggestion is to put indelible, glow-in-the-dark tattoos on the genitals of people infected with HIV. According to Duke, it may sound very draconian but it would not demean people. He also believes that tattooing would be legal because courts have a history of supporting the quarantining and institutionalizing of people with infectious diseases, such as tuberculosis. Duke said Cuba has had some success in using quarantines to reduce HIV infection, but he does not think it would work in the United States because it would cost too much. According to Duke, many people who get HIV from irresponsible behavior do not tell their partners that they have AIDS--these people are mad at the world and engage in dangerous behaviors even more. PMID:11362503

  17. Nuclear matrix association of the human beta-globin locus utilizing a novel approach to quantitative real-time PCR.

    PubMed

    Ostermeier, G Charles; Liu, Zhandong; Martins, Rui Pires; Bharadwaj, Rikki R; Ellis, James; Draghici, Sorin; Krawetz, Stephen A

    2003-06-15

    The human beta-globin locus is home to five genes that are regulated in a tissue-specific and developmental stage-specific manner. While the exact mode of expression remains somewhat enigmatic, a significant effort has been focused at the locus control region (LCR). The LCR is marked by five DNase I-hypersensitive sites (HS) approximately 15 kb upstream of the epsilon-globin gene. Nuclear matrix-associated regions (MARs) organize chromatin into functional domains and at least one of the HS appears bound to the nuclear matrix. We have employed an in vivo based PCR MAR assay to investigate the role of MAR-mediated regulation of the beta-globin locus. This was facilitated with a novel reaction efficiency based quantitative real-time PCR analysis software tool, Target Analysis Quantification. Using a log-linear regression strategy, discordances were eliminated. This allowed us to reliably estimate the relative amount of initial template associated with the nuclear matrix at 15 unique regions spanning the beta-globin locus in both non-expressing and expressing cell lines. A dynamic association dependent on expression status was revealed both at the LCR/5'HS region and within the second intron of the beta-globin gene. These results provide the first evidence that nuclear matrix association dynamically mediates the looping of the beta-globin locus to achieve transcriptional control.

  18. 76 FR 42159 - Lifting of Sanctions on Person Associated With the A.Q. Khan Nuclear Procurement Network

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-18

    ... were first imposed on January 16, 2009 (see 74 FR 3126, Jan 16, 2009; Public Notice 6486). Dated: July... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF STATE Lifting of Sanctions on Person Associated With the A.Q. Khan Nuclear Procurement Network AGENCY: Bureau...

  19. Reporting nuclear cardiology: a joint position paper by the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI).

    PubMed

    Trägårdh, Elin; Hesse, Birger; Knuuti, Juhani; Flotats, Albert; Kaufmann, Philipp A; Kitsiou, Anastasia; Hacker, Marcus; Verberne, Hein J; Edenbrandt, Lars; Delgado, Victoria; Donal, Erwan; Edvardsen, Thor; Galderisi, Maurizio; Habib, Gilbert; Lancellotti, Patrizio; Nieman, Koen; Rosenhek, Raphael; Agostini, Denis; Gimelli, Alessia; Lindner, Oliver; Slart, Riemert; Ubleis, Christopher

    2015-03-01

    The report of an imaging procedure is a critical component of an examination, being the final and often the only communication from the interpreting physician to the referring or treating physician. Very limited evidence and few recommendations or guidelines on reporting imaging studies are available; therefore, an European position statement on how to report nuclear cardiology might be useful. The current paper combines the limited existing evidence with expert consensus, previously published recommendations as well as current clinical practices. For all the applications discussed in this paper (myocardial perfusion, viability, innervation, and function as acquired by single photon emission computed tomography and positron emission tomography or hybrid imaging), headings cover laboratory and patient demographics, clinical indication, tracer administration and image acquisition, findings, and conclusion of the report. The statement also discusses recommended terminology in nuclear cardiology, image display, and preliminary reports. It is hoped that this statement may lead to more attention to create well-written and standardized nuclear cardiology reports and eventually lead to improved clinical outcome.

  20. A Cabinet of Mathematical Curiosities at Teachers College: David Eugene Smith's Collection

    ERIC Educational Resources Information Center

    Murray, Diane R.

    2012-01-01

    This dissertation is a history of David Eugene Smith's collection of historical books, manuscripts, portraits, and instruments related to mathematics. The study analyzes surviving documents, images, objects, college announcements and catalogs, and secondary sources related to Smith's collection. David Eugene Smith (1860-1944) travelled…

  1. Building Consensus toward a Shared Purpose: A Profile of President David Gray

    ERIC Educational Resources Information Center

    Dessoff, Alan

    2011-01-01

    The author presents a profile of APPA president David Gray. One might say that David Gray's path into higher education facilities management was anything but traditional. Today, Gray is the assistant vice president of facilities services at Middle Tennessee State University. His professional career, however, actually began in banking. In 1993 he…

  2. 77 FR 67725 - Culturally Significant Object Imported for Exhibition Determinations: “Michelangelo's David Apollo”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Culturally Significant Object Imported for Exhibition Determinations: ``Michelangelo's David Apollo'' SUMMARY... object to be included in the exhibition ``Michelangelo's David Apollo,'' imported from abroad for... display of the exhibit object at the National Gallery of Art, Washington, DC, from on or about December...

  3. Discussion of David Thissen's Bad Questions: An Essay Involving Item Response Theory

    ERIC Educational Resources Information Center

    Wainer, Howard

    2016-01-01

    The usual role of a discussant is to clarify and correct the paper being discussed, but in this case, the author, Howard Wainer, generally agrees with everything David Thissen says in his essay, "Bad Questions: An Essay Involving Item Response Theory." This essay expands on David Thissen's statement that there are typically two principal…

  4. Systematic and Statistical Errors Associated with Nuclear Decay Constant Measurements Using the Counting Technique

    NASA Astrophysics Data System (ADS)

    Koltick, David; Wang, Haoyu; Liu, Shih-Chieh; Heim, Jordan; Nistor, Jonathan

    2016-03-01

    Typical nuclear decay constants are measured at the accuracy level of 10-2. There are numerous reasons: tests of unconventional theories, dating of materials, and long term inventory evolution which require decay constants accuracy at a level of 10-4 to 10-5. The statistical and systematic errors associated with precision measurements of decays using the counting technique are presented. Precision requires high count rates, which introduces time dependent dead time and pile-up corrections. An approach to overcome these issues is presented by continuous recording of the detector current. Other systematic corrections include, the time dependent dead time due to background radiation, control of target motion and radiation flight path variation due to environmental conditions, and the time dependent effects caused by scattered events are presented. The incorporation of blind experimental techniques can help make measurement independent of past results. A spectrometer design and data analysis is reviewed that can accomplish these goals. The author would like to thank TechSource, Inc. and Advanced Physics Technologies, LLC. for their support in this work.

  5. Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy

    PubMed Central

    Changou, Chun A.; Chen, Yun-Ru; Xing, Li; Yen, Yun; Chuang, Frank Y. S.; Cheng, R. Holland; Bold, Richard J.; Ann, David K.; Kung, Hsing-Jien

    2014-01-01

    Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone-associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments. PMID:25122679

  6. Small nuclear ribonucleoprotein associated polypeptide N accelerates cell proliferation in pancreatic adenocarcinoma.

    PubMed

    Ma, Jin; Zhang, Zhuo; Wang, Jiancheng

    2015-10-01

    The spliceosome, the large RNA‑protein molecular complex, is crucial for pre‑mRNA splicing. Several antitumor drugs have been found to tightly bind to the components of the spliceosome and mutations in the spliceosome have been reported in several types of cancer. However, the involvement of the spliceosome in pancreatic adenocarcinoma remains unclear. In the present study, small nuclear ribonucleoprotein associated polypeptide N (SNRPN), a key constituent of spliceosomes, was disrupted in BxPC‑3 pancreatic adenocarcinoma cells using lentivirus‑mediated RNA interference (RNAi). It was found that knockdown of SNRPN reduced the proliferation ability of BxPC‑3 cells, as determined by an MTT assay. Furthermore, cell colony formation was impaired in SNRPN depleted adenocarcinoma cells and cell cycle analysis showed that depletion of SNRPN led to S phase cell cycle arrest and apoptosis. These results suggest that SNRPN is a key player in pancreatic adenocarcinoma cell growth, and targeted loss of SNRPN may be a potential therapeutic method for pancreatic cancer.

  7. Effect of small nuclear ribonucleoprotein-associated polypeptide N on the proliferation of medulloblastoma cells.

    PubMed

    Jing, Junjie; Zhao, Yang; Wang, Chengfeng; Zhao, Qingshuang; Liang, Qinchuan; Wang, Shousen; Ma, Jie

    2015-05-01

    Spliceosome mutations have been reported in various types of cancer and a number of antitumor drugs have been observed to tightly bind to spliceosome components. Small nuclear ribonucleoprotein‑associated polypeptide N (SNRPN) is a small ribonuclear protein and is a key spliceosome constituent. However, the role of SNRPN in human medulloblastoma remains unknown. In the present study, the effect of SNRPN on cell growth was investigated in vitro using the Daoy human medulloblastoma cell line. Lentivirus (Lv)-mediated short hairpin (sh) RNA was used to silence SNRPN expression, which was verified by reverse transcription‑quantitative polymerase chain reaction and western blotting. Cell proliferation was examined by MTT and colony formation assays. Knockdown of SNRPN markedly reduced the proliferation and colony formation ability of Daoy medulloblastoma cells. In addition, flow cytometric analysis revealed that the cell cycle distribution was altered when the Daoy cells were infected with Lv‑shSNRPN. To the best of our knowledge, this is the first study to investigate the effect of SNRPN on cell proliferation in medulloblastoma. The results indicate that SNRPN may be a potential novel target for the development of pharmacological therapeutics in human medulloblastoma.

  8. The haplotype-relative-risk (HRR) method for analysis of association in nuclear families

    SciTech Connect

    Knapp, M.; Seuchter, S.A.; Baur, M.P. )

    1993-06-01

    One major problem in studying an association between a marker locus and a disease is the selection of an appropriate group of controls. However, this problem of population stratification can be circumvented in a quite elegant manner by family-based methods. The haplotype-relative-risk (HRR) method, which samples nuclear families with a single affected child and uses the parental haplotypes not transmitted to that child as a control individual, represents such a method for estimating the relative risk of a marker phenotype. In the special case of a recessive disease, it was already known that the equivalence of the HRR method with the classical relative risk (RR) obtained from independent samples holds only if the probability [theta] of a recombination between marker and disease locus is zero. The authors extend this result to an arbitrary mode of inheritance. Furthermore, they compare the distribution of the estimators for HRR and RR and show that, in the case of a positive linkage disequilibrium between a marker and disease allele, the distribution of the estimator for HRR is (stochastically) smaller than that for RR, irrespective of the recombination fraction. The practical implication of this result is that, for the HRR method, there is no tendency to give unduly high risk estimators, even for [theta] > 0. Finally, the authors give an expression for the standard error of the estimator for HRR by taking into account the nonindependence of transmitted and nontransmitted parental marker alleles in the case of [theta] > 0. 16 refs., 3 tabs.

  9. Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy.

    PubMed

    Changou, Chun A; Chen, Yun-Ru; Xing, Li; Yen, Yun; Chuang, Frank Y S; Cheng, R Holland; Bold, Richard J; Ann, David K; Kung, Hsing-Jien

    2014-09-30

    Autophagy is the principal catabolic prosurvival pathway during nutritional starvation. However, excessive autophagy could be cytotoxic, contributing to cell death, but its mechanism remains elusive. Arginine starvation has emerged as a potential therapy for several types of cancers, owing to their tumor-selective deficiency of the arginine metabolism. We demonstrated here that arginine depletion by arginine deiminase induces a cytotoxic autophagy in argininosuccinate synthetase (ASS1)-deficient prostate cancer cells. Advanced microscopic analyses of arginine-deprived dying cells revealed a novel phenotype with giant autophagosome formation, nucleus membrane rupture, and histone-associated DNA leakage encaptured by autophagosomes, which we shall refer to as chromatin autophagy, or chromatophagy. In addition, nuclear inner membrane (lamin A/C) underwent localized rearrangement and outer membrane (NUP98) partially fused with autophagosome membrane. Further analysis showed that prolonged arginine depletion impaired mitochondrial oxidative phosphorylation function and depolarized mitochondrial membrane potential. Thus, reactive oxygen species (ROS) production significantly increased in both cytosolic and mitochondrial fractions, presumably leading to DNA damage accumulation. Addition of ROS scavenger N-acetyl cysteine or knockdown of ATG5 or BECLIN1 attenuated the chromatophagy phenotype. Our data uncover an atypical autophagy-related death pathway and suggest that mitochondrial damage is central to linking arginine starvation and chromatophagy in two distinct cellular compartments.

  10. A novel connexin50 mutation associated with congenital nuclear pulverulent cataracts

    PubMed Central

    Arora, A; Minogue, P J; Liu, X; Addison, P K; Russel-Eggitt, I; Webster, A R; Hunt, D M; Ebihara, L; Beyer, E C; Berthoud, V M; Moore, A T

    2009-01-01

    Purpose To screen for mutations of connexin50 (Cx50)/GJA8 in a panel of patients with inherited cataract and to determine the cellular and functional consequences of the identified mutation. Methods All patients in the study underwent a full clinical examination and leucocyte DNA was extracted from venous blood. The GJA8 gene was sequenced directly. Connexin function and cellular trafficking were examined by expression in Xenopus oocytes and HeLa cells. Results Screening of the GJA8 gene identified a 139 G to A transition that resulted in the replacement of aspartic acid by asparagine (D47N) in the coding region of Cx50. This change co-segregated with cataract among affected members of a family with autosomal dominant nuclear pulverulent cataracts. While pairs of Xenopus oocytes injected with wild type Cx50 RNA formed functional gap junction channels, pairs of oocytes injected with Cx50D47N showed no detectable intercellular conductance. Co-expression of Cx50D47N did not inhibit gap junctional conductance of wild type Cx50. In transiently transfected HeLa cells, wild type Cx50 localised to appositional membranes and within the perinuclear region, but Cx50D47N showed no immunostaining at appositional membranes with immunoreactivity confined to the cytoplasm. Incubation of HeLa cells transfected with Cx50D47N at 27°C resulted in formation of gap junctional plaques. Conclusions The pulverulent cataracts present in members of this family are associated with a novel GJA8 mutation, Cx50D47N, that acts as a loss-of-function mutation. The consequent decrease in lens intercellular communication and changes associated with intracellular retention of the mutant connexin may contribute to cataract formation. PMID:18006672

  11. Associated-particle sealed-tube neutron probe: Detection of explosives, contraband, and nuclear materials

    SciTech Connect

    Rhodes, E.; Dickerman, C.E.

    1996-05-01

    Continued research and development of the APSTNG shows the potential for practical field use of this technology for detection of explosives, contraband, and nuclear materials. The APSTNG (associated-particle sealed-tube generator) inspects the item to be examined using penetrating 14-MeV neutrons generated by the deuterium-tritium reaction inside a compact accelerator tube. An alpha detector built into the sealed tube detects the alpha-particle associated with each neutron emitted in a cone encompassing the volume to be inspected. Penetrating high-energy gamma-rays from the resulting neutron reactions identify specific nuclides inside the volume. Flight-times determined from the detection times of gamma-rays and alpha-particles separate the prompt and delayed gamma-ray spectra and allow a coarse 3-D image to be obtained of nuclides identified in the prompt spectrum. The generator and detectors can be on the same side of the inspected object, on opposite sides, or with intermediate orientations. Thus, spaces behind walls and other confined regions can be inspected. Signals from container walls can be discriminated against using the flight-time technique. No collimators or shielding are required, the neutron generator is relatively small, and commercial-grade electronics are employed. The use of 14-MeV neutrons yields a much higher cross-section for detecting nitrogen than that for systems based on thermal-neutron reactions alone, and the broad range of elements with significant 14-MeV neutron cross-sections extends explosives detection to other elements including low-nitrogen compounds, and allows detection of many other substances. Proof-of-concept experiments have been successfully performed for conventional explosives, chemical warfare agents, cocaine, and fissionable materials.

  12. Tissue-specific expression and cDNA cloning of small nuclear ribonucleoprotein-associated polypeptide N

    SciTech Connect

    McAllister, G.; Amara, S.G.; Lerner, M.R. )

    1988-07-01

    Sera from some patients with systemic lupus erythematosus and other autoimmune diseases have antibodies against nuclear antigens. An example is anti-Sm sera, which recognize proteins associated with small nuclear RNA molecules (small nuclear ribonucleoprotein (snRNP) particles). In this paper anti-Sm sera were used to probe immunoblots of various rat tissues. A previously unidentified M{sub r} 28,000 polypeptide was recognized by these anti-Sm sera. This polypeptide, referred to as N, is expressed in a tissue-specific manner, being most abundant in rat brain, less so in heart, and undetectable in the other tissues examined. Immunoprecipitation experiments using antibodies directed against the cap structure of small nuclear RNAs have demonstrated that N is a snRNP-associated polypeptide. Anti-Sm serum was also used to isolate a partial cDNA clone ({lambda}rb91) from a rat brain phage {lambda}gt11 cDNA expression library. A longer cDNA clone was obtained by rescreening the library with {lambda}rb91. In vitro transcription and subsequent translation of this subcloned, longer insert (pGMA2) resulted in a protein product with the same electrophoretic and immunological properties as N, confirming that pGMA2 encodes N. The tissue distribution of N and the involvement of snRNP particles in nuclear pre-mRNA processing may imply a role for N in tissue-specific pre-mRNA splicing.

  13. Nuclear translocation of the cytoskeleton-associated protein, smALP, upon induction of skeletal muscle differentiation

    SciTech Connect

    Cambier, Linda; Pomies, Pascal

    2011-06-17

    Highlights: {yields} The cytoskeleton-associated protein, smALP, is expressed in differentiated skeletal muscle. {yields} smALP is translocated from the cytoplasm to the nucleus of C2C12 myoblasts upon induction of myogenesis. {yields} The differentiation-dependent nuclear translocation of smALP occurs in parallel with the nuclear accumulation of myogenin. {yields} The LIM domain of smALP is essential for the nuclear accumulation of the protein. {yields} smALP might act in the nucleus to control some critical aspect of the muscle differentiation process. -- Abstract: The skALP isoform has been shown to play a critical role in actin organization and anchorage within the Z-discs of skeletal muscles, but no data is available on the function of the smALP isoform in skeletal muscle cells. Here, we show that upon induction of differentiation a nuclear translocation of smALP from the cytoplasm to the nucleus of C2C12 myoblasts, concomitant to an up-regulation of the protein expression, occurs in parallel with the nuclear accumulation of myogenin. Moreover, we demonstrate that the LIM domain of smALP is essential for the nuclear translocation of the protein.

  14. Proliferation dangers associated with nuclear medicine: getting weapons-grade uranium out of radiopharmaceutical production.

    PubMed

    Williams, Bill; Ruff, Tilman A

    2007-01-01

    Abolishing the threat of nuclear war requires the outlawing of nuclear weapons and dismantling current nuclear weapon stockpiles, but also depends on eliminating access to fissile material (nuclear weapon fuel). The near-universal use of weapons-grade, highly enriched uranium (HEU) to produce radiopharmaceuticals is a significant proliferation hazard. Health professionals have a strategic opportunity and obligation to progress the elimination of medically-related commerce in HEU, closing one of the most vulnerable pathways to the much-feared 'terrorist bomb'.

  15. Preparation of the Human Cytomegalovirus Nuclear Egress Complex and Associated Proteins.

    PubMed

    Sharma, Mayuri; Kamil, Jeremy P; Coen, Donald M

    2016-01-01

    Herpesviruses, like most DNA viruses, replicate their genomes in the host cell nucleus. Their DNA is then packaged and assembled into viral nucleocapsids, which, in most cases, are too large to pass through the nuclear pore complex. Instead, herpesviruses use a complex multistep pathway, termed nuclear egress, to exit the nucleus. Key players in this process include two conserved viral proteins that form the nuclear egress complex (NEC). In human cytomegalovirus, these NEC proteins are UL50, embedded in the inner nuclear membrane, and its nucleoplasmic partner UL53. Both are essential for viral nuclear egress. However, other viral components as well as host nuclear envelope proteins may also participate in nuclear egress. Identifying these viral and cellular factors may provide important insight into the herpesvirus lifecycle and its relationship to the underlying, yet still-mysterious, host nuclear egress pathway. We developed an immunoprecipitation-based protocol, described herein, to identify protein-protein interactions involving the NEC from the nuclear fraction of infected cells that express an epitope-tagged version of NEC subunit UL53.

  16. Kaposi's Sarcoma-Associated Herpesvirus (KSHV) Latency-Associated Nuclear Antigen Regulates the KSHV Epigenome by Association with the Histone Demethylase KDM3A

    PubMed Central

    Kim, Kevin Y.; Huerta, Steve B.; Izumiya, Chie; Wang, Don-Hong; Martinez, Anthony; Shevchenko, Bogdan; Kung, Hsing-Jien; Campbell, Mel

    2013-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) latent genomes are tethered to host histones to form a minichromosome also known as an “episome.” Histones, which are core components of chromatin, are heavily modified by various histone-targeting enzymes. Posttranslational modifications of histones significantly influence accessibility of transcriptional factors and thus have profound effects on gene expression. Recent studies showed that epigenetic marks on the KSHV episome are well organized, exemplified by the absence of histone H3 lysine 9 (H3K9) methylation, a heterochromatic histone mark, from immediate early and latent gene promoters in naturally infected cells. The present study revealed a mechanistic insight into KSHV epigenome regulation via a complex consisting of LANA and the H3K9me1/2 histone demethylase JMJD1A/KDM3A. This complex was isolated from HeLa cell nuclear extracts stably expressing LANA and was verified by coimmunoprecipitation analyses and with purified proteins. LANA recruitment sites on the KSHV genome inversely correlated with H3K9me2 histone marks in naturally infected cells, and methylation of H3K9 significantly inhibited LANA binding to the histone H3 tail. Chromatin immunoprecipitation coupled with KSHV tiling arrays identified the recruitment sites of the complex, while depletion of LANA expression or overexpression of a KDM3A binding-deficient mutant decreased KDM3A recruitment to the KSHV genome. Finally, ablation of KDM3A expression from latently KSHV-infected cells significantly inhibited KSHV gene expression, leading to decreased KSHV replication during reactivation. Taken together, our results suggest that LANA may play a role in regulation of epigenetic marks on the KSHV genome, which is in part through association with the histone demethylase KDM3A. PMID:23576503

  17. Quantum theory of concerted electronic and nuclear fluxes associated with adiabatic intramolecular processes.

    PubMed

    Bredtmann, Timm; Diestler, Dennis J; Li, Si-Dian; Manz, Jörn; Pérez-Torres, Jhon Fredy; Tian, Wen-Juan; Wu, Yan-Bo; Yang, Yonggang; Zhai, Hua-Jin

    2015-11-28

    An elementary molecular process can be characterized by the flow of particles (i.e., electrons and nuclei) that compose the system. The flow, in turn, is quantitatively described by the flux (i.e., the time-sequence of maps of the rate of flow of particles though specified surfaces of observation) or, in more detail, by the flux density. The quantum theory of concerted electronic and nuclear fluxes (CENFs) associated with electronically adiabatic intramolecular processes is presented. In particular, it is emphasized how the electronic continuity equation can be employed to circumvent the failure of the Born-Oppenheimer approximation, which always predicts a vanishing electronic flux density (EFD). It is also shown that all CENFs accompanying coherent tunnelling between equivalent "reactant" and "product" configurations of isolated molecules are synchronous. The theory is applied to three systems of increasing complexity. The first application is to vibrating, aligned H2(+)((2)Σg(+)), or vibrating and dissociating H2(+)((2)Σg(+), J = 0, M = 0). The EFD maps manifest a rich and surprising structure in this simplest of systems; for example, they show that the EFD is not necessarily synchronous with the nuclear flux density and can alternate in direction several times over the length of the molecule. The second application is to coherent tunnelling isomerization in the model inorganic system B4, in which all CENFs are synchronous. The contributions of core and valence electrons to the EFD are separately computed and it is found that core electrons flow with the nuclei, whereas the valence electrons flow obliquely to the core electrons in distinctive patterns. The third application is to the Cope rearrangement of semibullvalene, which also involves coherent tunnelling. An especially interesting discovery is that the so-called "pericyclic" electrons do not behave in the manner typically portrayed by the traditional Lewis structures with appended arrows. Indeed, it is

  18. Mortality and morbidity of members of the British Nuclear Tests Veterans Association and the New Zealand Nuclear Tests Veterans Association and their families.

    PubMed

    Roff, S R

    1999-01-01

    More than 20,000 British servicemen--many of them on their National Service, few of them volunteering for the tests, and most in their early twenties, some still boy soldiers in their teens--were required to 'participate' in the United Kingdom nuclear tests in Australia and Christmas Island in the 1950s and 1960s. 528 members of the New Zealand Navy were also present for one series of tests. There was also a Fijian Army contingent, which has been variously numbered between 100 and 500 men. An estimated 16,000 Australian servicemen and civilians were also involved in the tests at Maralinga and other sites. The men performed a wide range of duties, from highly technical preparations for the detonations to catering and clerical jobs. But whatever their role, they were all required to witness the detonations as part of their 'indoctrination' for the possibility of nuclear war. Most of them were required to line up on the beach, with their backs to the detonations and their hands over their eyes for the first minute or so. They were then allowed to turn around and look at the awesome sight as the mushroom cloud plumed thousands of feet into the air. Very few wore more than shorts and sandals during their time at the tests; only those who were thought to be at risk from radiation injury were issued with protective clothing and radiation dose badges. The UK government was sure that the troops, most of whom were standing within 20 km of the detonations and some of whom were present for 25 nuclear bomb blasts in as many weeks on Christmas Island, were not irradiated. The Ministry of Defence still routinely issues a document to nuclear veterans who feel that their illnesses were caused by the radiation they encountered when they were young men which states: The background [radiation] dose received by civilians and members of HM Forces serving at or off Christmas Island in the years 1956 to 1964 was only about 35% of that which they would have received on average had they

  19. Atmospheric release advisory capability pilot project at two nuclear power plants and associated state offices of emergency preparedness. Final report

    SciTech Connect

    Rosen, L.C.

    1983-01-01

    A project to demonstrate the feasibility of utilizing Atmospheric Release Advisory Capability (ARAC) limited service with commercial nuclear power plants and their associated state offices of emergency preparedness is discussed. Preliminary planning, installation and testing of the ARAC site facilities at Indian Point Nucler Power Station, New York State; at New York State Office of Emergency Preparedness, Albany, New York; at Rancho Seco Nuclear Generating Station, California; and at the State of California Office of Emergency Services, Sacramento, California, are summarized. ARAC participation in the Robert E. Ginna nuclear generating plant accident in New York on January 25, 1982, is discussed. The ARAC system is evaluated with emphasis on communications, the suite of models contained within the ARAC system, and the staff. The implications of this project in designing the next-generation ARAC system to service federal and state needs are assessed.

  20. Kaposi's sarcoma-associated herpesvirus LANA protein downregulates nuclear glycogen synthase kinase 3 activity and consequently blocks differentiation.

    PubMed

    Liu, Jianyong; Martin, Heather; Shamay, Meir; Woodard, Crystal; Tang, Qi-Qun; Hayward, S Diane

    2007-05-01

    The Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen (LANA) protein interacts with glycogen synthase kinase 3 (GSK-3) and relocalizes GSK-3 in a manner that leads to stabilization of beta-catenin and upregulation of beta-catenin-responsive cell genes. The LANA-GSK-3 interaction was further examined to determine whether there were additional downstream consequences. In the present study, the nuclear GSK-3 bound to LANA in transfected cells and in BCBL1 primary effusion lymphoma cells was found to be enriched for the inactive serine 9-phosphorylated form of GSK-3. The mechanism of inactivation of nuclear GSK-3 involved LANA recruitment of the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and the ribosomal S6 kinase 1 (RSK1). ERK1/2 and RSK1 coprecipitated with LANA, and LANA was a substrate for ERK1 in vitro. A model is proposed for the overall inactivation of nuclear GSK-3 that incorporates the previously described GSK-3 phosphorylation of LANA itself. Functional inactivation of nuclear GSK-3 was demonstrated by the ability of LANA to limit phosphorylation of the known GSK-3 substrates C/EBPbeta and C/EBPalpha. The effect of LANA-mediated ablation of C/EBP phosphorylation on differentiation was modeled in the well-characterized 3T3L1 adipogenesis system. LANA-expressing 3T3L1 cells were impaired in their ability to undergo differentiation and adipogenesis. C/EBPbeta induction followed the same time course as that seen in vector-transduced cells, but there was delayed and reduced induction of C/EBPbeta transcriptional targets in LANA-expressing cells. We conclude that LANA inactivates nuclear GSK-3 and modifies the function of proteins that are GSK-3 substrates. In the case of C/EBPs, this translates into LANA-mediated inhibition of differentiation. PMID:17314169

  1. Issues Associated with IAEA Involvement in Assured Nuclear Fuel Supply Arrangements

    SciTech Connect

    Kessler, Carol E.; Mathews, Carrie E.

    2008-02-08

    Assured nuclear fuel supply has been discussed at various times as a mechanism to help limit expansion of enrichment and reprocessing (E&R) capability beyond current technology holders. Given the events in the last few years in North Korea and Iran, concern over weapons capabilities gained from acquisition of E&R capabilities has heightened and brought assured nuclear fuel supply (AFS) again to the international agenda. Successful AFS programs can be valuable contributions to strengthening the nonproliferation regime and helping to build public support for expanding nuclear energy.

  2. Muscular Dystrophy-Associated SUN1 and SUN2 Variants Disrupt Nuclear-Cytoskeletal Connections and Myonuclear Organization

    PubMed Central

    Antoku, Susumu; Columbaro, Marta; Straatman, Kees R.; Worman, Howard J.; Gundersen, Gregg G.; Lattanzi, Giovanna; Wehnert, Manfred; Shackleton, Sue

    2014-01-01

    Proteins of the nuclear envelope (NE) are associated with a range of inherited disorders, most commonly involving muscular dystrophy and cardiomyopathy, as exemplified by Emery-Dreifuss muscular dystrophy (EDMD). EDMD is both genetically and phenotypically variable, and some evidence of modifier genes has been reported. Six genes have so far been linked to EDMD, four encoding proteins associated with the LINC complex that connects the nucleus to the cytoskeleton. However, 50% of patients have no identifiable mutations in these genes. Using a candidate approach, we have identified putative disease-causing variants in the SUN1 and SUN2 genes, also encoding LINC complex components, in patients with EDMD and related myopathies. Our data also suggest that SUN1 and SUN2 can act as disease modifier genes in individuals with co-segregating mutations in other EDMD genes. Five SUN1/SUN2 variants examined impaired rearward nuclear repositioning in fibroblasts, confirming defective LINC complex function in nuclear-cytoskeletal coupling. Furthermore, myotubes from a patient carrying compound heterozygous SUN1 mutations displayed gross defects in myonuclear organization. This was accompanied by loss of recruitment of centrosomal marker, pericentrin, to the NE and impaired microtubule nucleation at the NE, events that are required for correct myonuclear arrangement. These defects were recapitulated in C2C12 myotubes expressing exogenous SUN1 variants, demonstrating a direct link between SUN1 mutation and impairment of nuclear-microtubule coupling and myonuclear positioning. Our findings strongly support an important role for SUN1 and SUN2 in muscle disease pathogenesis and support the hypothesis that defects in the LINC complex contribute to disease pathology through disruption of nuclear-microtubule association, resulting in defective myonuclear positioning. PMID:25210889

  3. David de Wied: Eminent scientist and academic leader: A personal note.

    PubMed

    Gispen, Willem Hendrik

    2010-01-10

    David de Wied was a natural leader with many a talent. He was the director of the Rudolf Magnus Institute at Utrecht University and president of the Royal Netherlands Academy of Arts and Sciences. He coached over 75 Ph.D. students and hosted some 200 foreign scientists who joined him in his multidisciplinary neuropeptide research. Many of them became lifelong friends, frequenting the home of Liedje and David de Wied. Born in Deventer (The Netherlands) on January 12th, 1925, David de Wied's early boyhood first in Deventer and later in Leeuwarden appears to have been no different from that of any other provincial Dutch boys in pre-war Holland. After the war David enrolled at Groningen University to study medicine. Subsequently he specialized in experimental pharmacology. To understand the determination of David de Wied is to understand the drive of a Jewish young man, who during the war, had been forced to go underground and unable to develop in a free and independent manner. Therefore, later in life, time became very precious to him and everything that came across his path had to be taken seriously. In this short sketch of David de Wied I will try to highlight his outstanding scientific accomplishments as well as his personality as both have inspired a generation of young scientists. It is a great honour and a pleasure to be part of this meeting in memory of David de Wied.

  4. Identification and characterisation of a nuclear localisation signal in the SMN associated protein, Gemin4

    SciTech Connect

    Lorson, Monique A.; Dickson, Alexa M.; Shaw, Debra J.; Todd, Adrian G.; Young, Elizabeth C.; Morse, Robert; Wolstencroft, Catherine; Lorson, Christian L.; Young, Philip J.

    2008-10-10

    Gemin4 is a ubiquitously expressed multifunctional protein that is involved in U snRNP assembly, apoptosis, nuclear/cytoplasmic transportation, transcription, and RNAi pathways. Gemin4 is one of the core components of the Gemin-complex, which also contains survival motor neuron (SMN), the seven Gemin proteins (Gemin2-8), and Unrip. Mutations in the SMN1 gene cause the autosomal recessive disorder spinal muscular atrophy (SMA). Although the functions assigned to Gemin4 predominantly occur in the nucleus, the mechanisms that mediate the nuclear import of Gemin4 remain unclear. Here, using a novel panel of Gemin4 constructs we identify a canonical nuclear import sequence (NLS) in the N-terminus of Gemin4. The Gemin4 NLS is necessary and independently sufficient to mediate nuclear import of Gemin4. This is the first functional NLS identified within the SMN-Gemin complex.

  5. Sir David Wilkie (1882-1938): surgeon, scientist and philanthropist.

    PubMed

    Macintyre, Iain

    2007-11-01

    Until the start of the 20th century, appointment to a chair in surgery in Britain was usually awarded in recognition of an already successful career. Sir David Wilkie was among the first of the new breed of professors of surgery appointed at a relatively young age to develop surgical research and undergraduate teaching. At the University of Edinburgh, he established a surgical research laboratory from which was to emerge a cohort of young surgical researchers destined to become the largest dynasty of surgical professors yet seen in the British Isles. He is widely regarded as the father of British academic surgery. Born in the same Scottish village as the writer JM Barrie (1860-1937), like Barrie, Wilkie became a philanthropist. Both men were to achieve eminence in later life and when Barrie was appointed Chancellor of Edinburgh University, their friendship developed. Barrie's legacy to Great Ormond Street Children's Hospital was one of the greatest ever acts of medical philanthropy, and Wilkie too proved to be a generous benefactor of the disadvantaged.

  6. The Small Nuclear Genomes of Selaginella Are Associated with a Low Rate of Genome Size Evolution

    PubMed Central

    Baniaga, Anthony E.; Arrigo, Nils; Barker, Michael S.

    2016-01-01

    The haploid nuclear genome size (1C DNA) of vascular land plants varies over several orders of magnitude. Much of this observed diversity in genome size is due to the proliferation and deletion of transposable elements. To date, all vascular land plant lineages with extremely small nuclear genomes represent recently derived states, having ancestors with much larger genome sizes. The Selaginellaceae represent an ancient lineage with extremely small genomes. It is unclear how small nuclear genomes evolved in Selaginella. We compared the rates of nuclear genome size evolution in Selaginella and major vascular plant clades in a comparative phylogenetic framework. For the analyses, we collected 29 new flow cytometry estimates of haploid genome size in Selaginella to augment publicly available data. Selaginella possess some of the smallest known haploid nuclear genome sizes, as well as the lowest rate of genome size evolution observed across all vascular land plants included in our analyses. Additionally, our analyses provide strong support for a history of haploid nuclear genome size stasis in Selaginella. Our results indicate that Selaginella, similar to other early diverging lineages of vascular land plants, has relatively low rates of genome size evolution. Further, our analyses highlight that a rapid transition to a small genome size is only one route to an extremely small genome. PMID:27189987

  7. Analysis of the formation, expression, and economic impacts of risk perceptions associated with nuclear facilities

    SciTech Connect

    Allison, T.; Hunter, S.; Calzonetti, F.J.

    1992-10-01

    This report investigates how communities hosting nuclear facilities form and express perceptions of risk and how these risk perceptions affect local economic development. Information was collected from site visits and interviews with plant personnel, officials of local and state agencies, and community activists in the hosting communities. Six commercial nuclear fuel production facilities and five nuclear facilities operated for the US Department of Energy by private contractors were chosen for analysis. The results presented in the report indicate that the nature of risk perceptions depends on a number of factors. These factors are (1) level of communication by plant officials within the local community, (2) track record of the facility. operator, (3) process through which community and state officials receive information and form opinions, (4) level of economic links each plant has with the local community, and (15) physical characteristics of the facility itself. This report finds that in the communities studied, adverse ask perceptions have not affected business location decisions, employment levels in the local community, tourism, or agricultural development. On the basis of case-study findings, this report recommends that nuclear facility siting programs take the following observations into account when addressing perceptions of risk. First, the quality of a facility`s participation with community activists, interest groups, and state agencies helps to determine the level of perceived risk within a community. Second, the development of strong economic links between nuclear facilities and their host communities will produce a higher level of acceptance of the nuclear facilities.

  8. Solid cancer mortality associated with chronic external radiation exposure at the French atomic energy commission and nuclear fuel company.

    PubMed

    Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

    2011-07-01

    Studies of nuclear workers make it possible to directly quantify the risks associated with ionizing radiation exposure at low doses and low dose rates. Studies of the CEA (Commissariat à l'Energie Atomique) and AREVA Nuclear Cycle (AREVA NC) cohort, currently the most informative such group in France, describe the long-term risk to nuclear workers associated with external exposure. Our aim is to assess the risk of mortality from solid cancers among CEA and AREVA NC nuclear workers and its association with external radiation exposure. Standardized mortality ratios (SMRs) were calculated and internal Poisson regressions were conducted, controlling for the main confounding factors [sex, attained age, calendar period, company and socioeconomic status (SES)]. During the period 1968-2004, there were 2,035 solid cancers among the 36,769 CEA-AREVA NC workers. Cumulative external radiation exposure was assessed for the period 1950-2004, and the mean cumulative dose was 12.1 mSv. Mortality rates for all causes and all solid cancers were both significantly lower in this cohort than in the general population. A significant excess of deaths from pleural cancer, not associated with cumulative external dose, was observed, probably due to past asbestos exposure. We observed a significant excess of melanoma, also unassociated with dose. Although cumulative external dose was not associated with mortality from all solid cancers, the central estimated excess relative risk (ERR) per Sv of 0.46 for solid cancer mortality was higher than the 0.26 calculated for male Hiroshima and Nagasaki A-bomb survivors 50 years or older and exposed at the age of 30 years or older. The modification of our results after stratification for SES demonstrates the importance of this characteristic in occupational studies, because it makes it possible to take class-based lifestyle differences into account, at least partly. These results show the great potential of a further joint international study of

  9. The GIP gamma-tubulin complex-associated proteins are involved in nuclear architecture in Arabidopsis thaliana

    PubMed Central

    Batzenschlager, Morgane; Masoud, Kinda; Janski, Natacha; Houlné, Guy; Herzog, Etienne; Evrard, Jean-Luc; Baumberger, Nicolas; Erhardt, Mathieu; Nominé, Yves; Kieffer, Bruno; Schmit, Anne-Catherine; Chabouté, Marie-Edith

    2013-01-01

    During interphase, the microtubular cytoskeleton of cycling plant cells is organized in both cortical and perinuclear arrays. Perinuclear microtubules (MTs) are nucleated from γ-Tubulin Complexes (γ-TuCs) located at the surface of the nucleus. The molecular mechanisms of γ-TuC association to the nuclear envelope (NE) are currently unknown. The γ-TuC Protein 3 (GCP3)-Interacting Protein 1 (GIP1) is the smallest γ-TuC component identified so far. AtGIP1 and its homologous protein AtGIP2 participate in the localization of active γ-TuCs at interphasic and mitotic MT nucleation sites. Arabidopsis gip1gip2 mutants are impaired in establishing a fully functional mitotic spindle and exhibit severe developmental defects. In this study, gip1gip2 knock down mutants were further characterized at the cellular level. In addition to defects in both the localization of γ-TuC core proteins and MT fiber robustness, gip1gip2 mutants exhibited a severe alteration of the nuclear shape associated with an abnormal distribution of the nuclear pore complexes. Simultaneously, they showed a misorganization of the inner nuclear membrane protein AtSUN1. Furthermore, AtGIP1 was identified as an interacting partner of AtTSA1 which was detected, like the AtGIP proteins, at the NE. These results provide the first evidence for the involvement of a γ-TuC component in both nuclear shaping and NE organization. Functional hypotheses are discussed in order to propose a model for a GIP-dependent nucleo-cytoplasmic continuum. PMID:24348487

  10. Nitric oxide induces thioredoxin-1 nuclear translocation: Possible association with the p21Ras survival pathway

    SciTech Connect

    Arai, Roberto J.; Yodoi, J.; Debbas, V.; Laurindo, Francisco R.; Stern, A.; Monteiro, Hugo P. . E-mail: hpmonte@uol.com.br

    2006-10-06

    One of the major redox-regulating molecules with thiol reducing activity is thioredoxin-1 (TRX-1). TRX-1 is a multifunctional protein that exists in the extracellular millieu, cytoplasm, and nucleus, and has a distinct role in each environment. It is well known that TRX-1 promptly migrates to the nuclear compartment in cells exposed to oxidants. However, the intracellular location of TRX-1 in cells exposed to nitrosothiols has not been investigated. Here, we demonstrated that the exposure of HeLa cells to increasing concentrations of the nitrosothiol S-nitroso-N-acetylpenicillamine (SNAP) promoted TRX-1 nuclear accumulation. The SNAP-induced TRX-1 translocation to the nucleus was inhibited by FPTIII, a selective inhibitor of p21Ras. Furthermore, TRX-1 migration was attenuated in cells stably transfected with NO insensitive p21Ras (p21{sup RasC118S}). Downstream to p21Ras, the MAP Kinases ERK1/2 were activated by SNAP under conditions that promote TRX-1 nuclear translocation. Inhibition of MEK prevented SNAP-stimulated ERK1/2 activation and TRX-1 nuclear migration. In addition, cells treated with p21Ras or MEK inhibitor showed increased susceptibility to cell death induced by SNAP. In conclusion, our observations suggest that the nuclear translocation of TRX-1 is induced by SNAP involving p21Ras survival pathway.

  11. Systematic Identification of Novel Protein Domain Families Associated with Nuclear Functions

    PubMed Central

    Doerks, Tobias; Copley, Richard R.; Schultz, Jörg; Ponting, Chris P.; Bork, Peer

    2002-01-01

    A systematic computational analysis of protein sequences containing known nuclear domains led to the identification of 28 novel domain families. This represents a 26% increase in the starting set of 107 known nuclear domain families used for the analysis. Most of the novel domains are present in all major eukaryotic lineages, but 3 are species specific. For about 500 of the 1200 proteins that contain these new domains, nuclear localization could be inferred, and for 700, additional features could be predicted. For example, we identified a new domain, likely to have a role downstream of the unfolded protein response; a nematode-specific signalling domain; and a widespread domain, likely to be a noncatalytic homolog of ubiquitin-conjugating enzymes. PMID:11779830

  12. Astronaut David Wolf draws blood from Martin Fettman for SLS-2 investigations

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Inside the science module aboard the Earth-orbiting Space Shuttle Columbia, Astronaut David A. Wolf draws blood from payload specialists Martin J. Fettman, DVM. Blood samples from crew members are critical to several Spacelab Life Sciences (SLS-2) investigations.

  13. An Inside View: Investigative Reporter David Weir on Searching for the Truth.

    ERIC Educational Resources Information Center

    Brown, Donal

    1986-01-01

    Discusses the work of David Weir, who believes that reporters need to cultivate open-mindedness, detachment from their own work, and ability to see beyond their own prejudices and predispositions to alter hypotheses to fit the facts. (SRT)

  14. High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

    PubMed Central

    2009-01-01

    Background Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Methods Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. Results The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. Conclusion The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer. PMID:19878561

  15. N-terminal determinants of human cytomegalovirus IE1 protein in nuclear targeting and disrupting PML-associated subnuclear structures

    SciTech Connect

    Lee, Hye-Ra; Huh, Yong Ho; Kim, Young-Eui; Lee, Karim; Kim, Sunyoung; Ahn, Jin-Hyun . E-mail: jahn@med.skku.ac.kr

    2007-05-04

    The 72-kDa IE1 protein of human cytomegalovirus disrupts PML-associated subnuclear structures (PODs) by inducing PML desumoylation. This process correlates with the functions of IE1 in transcriptional regulation and efficient viral replication. Here, we defined the N-terminal regions of IE1 required for nuclear targeting and POD-disrupting activity. Although the 24 N-terminal amino acids encoded by exon 2, which were previously shown to be essential for nuclear targeting, did not appear to contain typical basic nuclear localization signals, these residues were able to efficiently convey the GFP protein into the nucleus, suggesting a role in promoting nuclear translocation. In assays using a series of N-terminal truncation IE1 mutants, which were forced to enter the nucleus, exon 2 was completely dispensable for POD disruption. However, the predicted two {alpha}-helix regions in exon 3 were identified as important structural determinants for protein stability and for the correlating activities in POD disruption and PML desumoylation.

  16. Nuclear heat shock protein 110 expression is associated with poor prognosis and chemotherapy resistance in gastric cancer.

    PubMed

    Kimura, Akiharu; Ogata, Kyoichi; Altan, Bolag; Yokobori, Takehiko; Ide, Munenori; Mochiki, Erito; Toyomasu, Yoshitaka; Kogure, Norimichi; Yanoma, Toru; Suzuki, Masaki; Bai, Tuya; Oyama, Tetsunari; Kuwano, Hiroyuki

    2016-04-01

    Heat shock protein (HSP) expression is induced by the exposure to stress, such as fever, oxidative stress, chemical exposure, and irradiation. In cancer, HSP promotes the survival of malignant cells by inhibiting the induction of apoptosis. In colorectal cancer, a loss-of-function mutation of HSP110 (HSP110ΔE9) has been identified. HSP110ΔE9 inhibits the nuclear translocation of wild-type HSP110, which is important for its chaperone activity and anti-apoptotic effects. The patients carrying HSP110ΔE9 mutation exhibit high sensitivity to anticancer agents, such as oxaliplatin and 5-fluorouracil. There is still insufficient information about HSP110 localization, the clinicopathological significance of HSP110 expression, and its association with chemotherapy resistance in gastric cancer. Here, we found that high nuclear expression of HSP110 in gastric cancer tissues is associated with cancer progression, poor prognosis, and recurrence after adjuvant chemotherapy. In vitro results showed that HSP110 suppression increases the sensitivity to 5-fluorouracil and cisplatin of human gastric cancer cell lines. Our results suggest that nuclear HSP110 may be a new drug sensitivity marker for gastric cancer and a potential molecular therapeutic target for the treatment of gastric cancer patients with acquired anticancer drug resistance. PMID:26943774

  17. Nuclear heat shock protein 110 expression is associated with poor prognosis and chemotherapy resistance in gastric cancer

    PubMed Central

    Kimura, Akiharu; Ogata, Kyoichi; Altan, Bolag; Yokobori, Takehiko; Ide, Munenori; Mochiki, Erito; Toyomasu, Yoshitaka; Kogure, Norimichi; Yanoma, Toru; Suzuki, Masaki; Bai, Tuya; Oyama, Tetsunari; Kuwano, Hiroyuki

    2016-01-01

    Heat shock protein (HSP) expression is induced by the exposure to stress, such as fever, oxidative stress, chemical exposure, and irradiation. In cancer, HSP promotes the survival of malignant cells by inhibiting the induction of apoptosis. In colorectal cancer, a loss-of-function mutation of HSP110 (HSP110ΔE9) has been identified. HSP110ΔE9 inhibits the nuclear translocation of wild-type HSP110, which is important for its chaperone activity and anti-apoptotic effects. The patients carrying HSP110ΔE9 mutation exhibit high sensitivity to anticancer agents, such as oxaliplatin and 5-fluorouracil. There is still insufficient information about HSP110 localization, the clinicopathological significance of HSP110 expression, and its association with chemotherapy resistance in gastric cancer. Here, we found that high nuclear expression of HSP110 in gastric cancer tissues is associated with cancer progression, poor prognosis, and recurrence after adjuvant chemotherapy. In vitro results showed that HSP110 suppression increases the sensitivity to 5-fluorouracil and cisplatin of human gastric cancer cell lines. Our results suggest that nuclear HSP110 may be a new drug sensitivity marker for gastric cancer and a potential molecular therapeutic target for the treatment of gastric cancer patients with acquired anticancer drug resistance. PMID:26943774

  18. SUMO-1 promotes association of SNURF (RNF4) with PML nuclear bodies

    SciTech Connect

    Haekli, Marika; Karvonen, Ulla; Jaenne, Olli A.; Palvimo, Jorma J. . E-mail: jorma.palvimo@helsinki.fi

    2005-03-10

    Small nuclear RING finger protein SNURF (RNF4) is involved in transcriptional and cell growth regulation. We show here that a significant portion of endogenous SNURF localizes to nuclear bodies (NBs) that overlap with or are adjacent to domains containing endogenous promyelocytic leukemia (PML) protein and small ubiquitin-like modifier-1 (SUMO-1). In biochemical assays, SNURF efficiently binds SUMO-1 in a noncovalent fashion. SNURF is also covalently modified by SUMO-1 at nonconsensus attachment sites. Ectopic expression of SUMO-1 markedly enhances the interaction between PML3 (PML IV) and SNURF, but covalent attachment of SUMO-1 to neither protein is required. Moreover, overexpression of PML3, but not PML-L (PML III), abolishes the coactivation function of SNURF in transactivation assays, which parallels the ability of PML3 to recruit SNURF to nuclear bodies. In sum, we have identified SNURF as a novel component in PML bodies and suggest that SUMO-1-facilitated sequestration into these nuclear domains regulates the transcriptional activity of SNURF.

  19. CORROSION ISSUES ASSOCIATED WITH AUSTENITIC STAINLESS STEEL COMPONENTS USED IN NUCLEAR MATERIALS EXTRACTION AND SEPARATION PROCESSES

    SciTech Connect

    Mickalonis, J.; Louthan, M.; Sindelar, R.

    2012-12-17

    This paper illustrated the magnitude of the systems, structures and components used at the Savannah River Site for nuclear materials extraction and separation processes. Corrosion issues, including stress corrosion cracking, pitting, crevice corrosion and other corrosion induced degradation processes are discussed and corrosion mitigation strategies such as a chloride exclusion program and corrosion release testing are also discussed.

  20. Genome Assembly of Citrus Leprosis Virus Nuclear Type Reveals a Close Association with Orchid Fleck Virus

    PubMed Central

    Stone, Andrew; Otero-Colina, Gabriel; Wei, Gang; Choudhary, Nandlal; Achor, Diann; Shao, Jonathan; Levy, Laurene; Nakhla, Mark K.; Hollingsworth, Charla R.; Hartung, John S.; Schneider, William L.

    2013-01-01

    The complete genome of citrus leprosis virus nuclear type (CiLV-N) was identified by small RNA sequencing utilizing leprosis-affected citrus samples collected from the state of Querétaro, Mexico. The nucleotide identity and phylogenetic analysis indicate that CiLV-N is very closely related to orchid fleck virus, which typically infects Cymbidium species. PMID:23887919

  1. Characterization of ribonucleoprotein complexes containing an abundant polyadenylated nuclear RNA encoded by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8).

    PubMed Central

    Zhong, W; Ganem, D

    1997-01-01

    Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8) is strongly linked to all forms of Kaposi's sarcoma. We have previously identified two polyadenylated KSHV transcripts that are actively transcribed in Kaposi's sarcoma (KS) tumors and in KSHV-infected B-lymphoma cells. One of these RNAs (termed T1.1 or nut-1 RNA) is a 1.1-kb transcript present in a subpopulation of KS tumor cells. This RNA is localized to the nucleus of infected cells and has no open reading frames longer than 62 codons, suggesting that it may not function as an mRNA in vivo. Here we demonstrate that nut-1 RNA is a lytic-cycle gene product that is found in high-molecular-weight ribonucleoprotein complexes in infected cell nuclei. The transcript lacks the trimethylguanosine (TMG) cap found in many U-like small nuclear RNAs, but a subpopulation of nut-1 RNAs can associate with Sm protein-containing small nuclear ribonucleoproteins, as judged by immunoprecipitation analyses using monoclonal anti-Sm and anti-TMG antibodies. This interaction does not require other viral gene products, and deletion of the sole candidate Sm binding site on nut-1 RNA does not ablate this association. This finding suggests an indirect interaction with Sm-containing structures, and models for such associations are presented. PMID:8995643

  2. Nuclear import of RNA polymerase II is coupled with nucleocytoplasmic shuttling of the RNA polymerase II-associated protein 2.

    PubMed

    Forget, Diane; Lacombe, Andrée-Anne; Cloutier, Philippe; Lavallée-Adam, Mathieu; Blanchette, Mathieu; Coulombe, Benoit

    2013-08-01

    The RNA polymerase II (RNAP II)-associated protein (RPAP) 2 has been discovered through its association with various subunits of RNAP II in affinity purification coupled with mass spectrometry experiments. Here, we show that RPAP2 is a mainly cytoplasmic protein that shuttles between the cytoplasm and the nucleus. RPAP2 shuttling is tightly coupled with nuclear import of RNAP II, as RPAP2 silencing provokes abnormal accumulation of RNAP II in the cytoplasmic space. Most notably, RPAP4/GPN1 silencing provokes the retention of RPAP2 in the nucleus. Our results support a model in which RPAP2 enters the nucleus in association with RNAP II and returns to the cytoplasm in association with the GTPase GPN1/RPAP4. Although binding of RNAP II to RPAP2 is mediated by an N-terminal domain (amino acids 1-170) that contains a nuclear retention domain, and binding of RPAP4/GPN1 to RPAP2 occurs through a C-terminal domain (amino acids 156-612) that has a dominant cytoplasmic localization domain. In conjunction with previously published data, our results have important implications, as they indicate that RPAP2 controls gene expression by two distinct mechanisms, one that targets RNAP II activity during transcription and the other that controls availability of RNAP II in the nucleus.

  3. Inductively Coupled Plasma/Mass Spectrometric Isotopic Determination of Nuclear Wastes Sources Associated with Hanford Tank Leaks

    SciTech Connect

    Evans, John C.; Dresel, P. Evan; Farmer, Orville T.

    2007-11-01

    The subsurface distribution of a nuclear waste tank leak on the U.S. Department of Energy’s Hanford Site was sampled by slant drilling techniques in order to characterize the chemical and radiological characteristics of the leaked material and assess geochemical transport properties of hazardous constituents. Sediment core samples recovered from the borehole were subjected to distilled water and acid leaching procedures with the resulting leachates analyzed for isotopic and chemical signatures. High-sensitivity inductively coupled plasma/mass spectrometry (ICP/MS) techniques were used for determination of isotopic ratios for Cs, I, Mo. Analysis of the isotopic patterns of I and Mo combined with associated chemical data showed evidence for at least two separate intrusions of nuclear waste into the subsurface. Isotopic data for Cs was inconclusive with respect to a source attribution signature.

  4. Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease.

    PubMed

    Liu, Rugao; Lei, Joy X; Luo, Chun; Lan, Xun; Chi, Liying; Deng, Panyue; Lei, Saobo; Ghribi, Othman; Liu, Qing Yan

    2012-03-01

    Though loss of function in CBP/p300, a family of CREB-binding proteins, has been causally associated with a variety of human neurological disorders, such as Rubinstein-Taybi syndrome, Huntington's disease and drug addiction, the role of EP300 interacting inhibitor of differentiation 1 (EID1), a CBP/p300 inhibitory protein, in modulating neurological functions remains completely unknown. Through the examination of EID1 expression and cellular distribution, we discovered that there is a significant increase of EID1 nuclear translocation in the cortical neurons of Alzheimer's disease (AD) patient brains compared to that of control brains. To study the potential effects of EID1 on neurological functions associated with learning and memory, we generated a transgenic mouse model with a neuron-specific expression of human EID1 gene in the brain. Overexpression of EID1 led to an increase in its nuclear localization in neurons mimicking that seen in human AD brains. The transgenic mice had a disrupted neurofilament organization and increase of astrogliosis in the cortex and hippocampus. Furthermore, we demonstrated that overexpression of EID1 reduced hippocampal long-term potentiation and impaired spatial learning and memory function in the transgenic mice. Our results indicated that the negative effects of extra nuclear EID1 in transgenic mouse brains are likely due to its inhibitory function on CBP/p300 mediated histone and p53 acetylation, thus affecting the expression of downstream genes involved in the maintenance of neuronal structure and function. Together, our data raise the possibility that alteration of EID1 expression, particularly the increase of EID1 nuclear localization that inhibits CBP/p300 activity in neuronal cells, may play an important role in AD pathogenesis. PMID:22186421

  5. Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

    PubMed Central

    Olivares, Ana Maria; Moreno-Ramos, Oscar Andrés; Haider, Neena B.

    2015-01-01

    The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration. PMID:27168725

  6. Nuclear alterations associated to programmed cell death in larval salivary glands of Apis mellifera (Hymenoptera: Apidae).

    PubMed

    Silva-Zacarin, E C M; Taboga, S R; Silva de Moraes, R L M

    2008-01-01

    The silk glands of bees are a good model for the study of cell death in insects. With the objective to detect the nuclear features during glandular regression stage, larvae at the last instar and pre-pupae were collected and their silk glands were dissected and processed for ultrastructural analysis and histologically for cytochemical and imunocytochemical analysis. The results showed that the cellular nuclei exhibited characteristics of death by atypical apoptosis as well as autophagic cell death. Among the apoptosis characteristic were: nuclear strangulation with bleb formation in some nuclei, DNA fragmentation in most of the nuclei and nucleolar fragmentation. Centripetal chromatin compaction was observed in many nuclei, forming a perichromatin halo differing from typical apoptotic nuclei. With regards to the characteristics of autophagic-programmed cell death, most relevant was the delay in the collapse of many nuclei.

  7. David Triggle: Research collaborations and scientific exchanges with the China Pharmaceutical University, Nanjing, China.

    PubMed

    Dai, De-Zai

    2015-11-15

    Over the period 1995-2012, David Triggle was a frequent visitor to the China Pharmaceutical University in Nanjing, China making many important contributions that enhanced the activities of the Research Division of Pharmacology at the University. In addition to providing collegial advice and facilitating interactions with the international pharmacological community, Professor Triggle's international reputation as a thought leader in the field of ion channel research and drug discovery provided important insights into the potential pathophysiological and therapeutic effects of targeting ion channels. This included the L-type calcium channel and the outward delayed rectified potassium currents of rapid (IKr) and slow (IKs) components in the myocardium. The Nanjing research team had been particularly interested in ion channel dysfunction in the context of cardiac arrhythmias, remodeling and drug discovery. With Professor Triggle's assistance, the relationship between an increase in ICa.L and other biological events including an enhancement of IKr and IKr currents, NADPH oxidase and endothelin receptor activation, down regulation of calcium modulating protein FKBP12.6, sarco/endoplasmic reticulum Ca(2+)ATPse (SERCA2A) and calsequens 2 (CASQ2), calcium leak at the diastole and endoplasmic reticulum stress, were evaluated and are discussed. Additionally, the organization of several international symposia was greatly enhanced by input from Professor Triggle as were the published research manuscripts in international pharmacology journals. During his association with the China Pharmaceutical University, Professor Triggle aided in enhancing the scientific standing of the Pharmacology department and was a highly effective ambassador for international research cooperation.

  8. Behavioral differences of irradiated persons associated with the Kyshtym, Chelyabinsk, and Chernobyl nuclear accidents.

    PubMed

    Collins, D L

    1992-10-01

    Three nuclear accidents besides Chernobyl have occurred in the former Soviet Union. The accidents occurred around Kyshtym and Chelyabinsk in the Ural Mountains between 1949 and 1967 and contaminated over one-half million people. The health ministries are now interested in the data previously collected on these irradiated populations in order to examine the health (e.g., psychological, hereditary, genome damage, etc.) implications of long-term radiation exposure.

  9. Safety-related issues associated with implementing wireless systems in nuclear facilities

    SciTech Connect

    Kaldenbach, B. J.; Ewing, P. D.; Moore, M. R.; Korsah, K.; Antonescu, C. E.; Govan, T. V.

    2006-07-01

    Currently, wireless technology is not used as an integral element of safety-related systems in nuclear facilities. The most prevalent introductory uses of wireless technology are for in-facility communications among personnel and for supplemental information transmission. However, further system upgrades and implementations at new facilities might introduce wireless communications into safety-significant applications. This paper documents the deployment issues and implementation considerations that can contribute to the technical basis for guidance on wireless systems. (authors)

  10. Distribution of nuclear mitochondrial pseudogenes in three pollinator fig wasps associated with Ficus pumila

    NASA Astrophysics Data System (ADS)

    Chen, Yan; Liu, Min; Compton, Stephen G.; Chen, Xiao-Yong

    2014-05-01

    Nuclear mitochondrial pseudogenes (NUMTs) are nuclear sequences transferred from mitochondrial genomes. Although widespread, their distribution patterns among populations or closely related species are rarely documented. We amplified and sequenced the mitochondrial cytochrome b (Cytb) gene to check for NUMTs in three fig wasp species that pollinate Ficus pumila (Wiebesia sp. 1, 2 and 3) in Southeastern China using direct and cloned sequencing. Unambiguous sequences (332) of 487 bp in length belonging to 33 haplotypes were found by direct sequencing. Their distribution was highly concordant with those of cytochrome c oxidase subunit I (COI). Obvious signs of co-amplification of NUMTs were indicated by their uneven distribution. NUMTs were observed in all individuals of 12 populations of Wiebesia sp. 3, and 13 individuals of three northern populations of Wiebesia sp. 1. Sequencing clones of potential co-amplification products confirmed that they were NUMTs. These NUMTs either clustered as NUMT clades basal to mtDNA Cytb clades (basal NUMTs), or together with Cytb haplotypes. Basal NUMTs had either stop codons or frame-shifting mutations resulting from deletion of a 106 bp fragment. In addition, no third codon or synonymous substitutions were detected within each NUMT clade. The phylogenetic tree indicated that basal NUMTs had been inserted into nuclei before divergence of the three species. No significant pairwise differences were detected in their ratios of third codon substitutions, suggesting that these NUMTs originated from one transfer event, with duplication in the nuclear genome resulting in the coexistence of the 381 bp copy. No significant substitution differences were detected between Cytb haplotypes and NUMTs that clustered with Cytb haplotypes. However, these NUMTs coexisted with Cytb haplotypes in multiple populations, suggesting that these NUMT haplotypes were recently inserted into the nuclear genome. Both basal and recently inserted NUMTs were rare

  11. Behavioral differences of irradiated persons associated with the Kyshtym, Chelyabinsk, and Chernobyl nuclear accidents.

    PubMed

    Collins, D L

    1992-10-01

    Three nuclear accidents besides Chernobyl have occurred in the former Soviet Union. The accidents occurred around Kyshtym and Chelyabinsk in the Ural Mountains between 1949 and 1967 and contaminated over one-half million people. The health ministries are now interested in the data previously collected on these irradiated populations in order to examine the health (e.g., psychological, hereditary, genome damage, etc.) implications of long-term radiation exposure. PMID:1454181

  12. Dss1 associating with the proteasome functions in selective nuclear mRNA export in yeast

    SciTech Connect

    Mannen, Taro; Andoh, Tomoko; Tani, Tokio

    2008-01-25

    Dss1p is an evolutionarily conserved small protein that interacts with BRCA2, a tumor suppressor protein, in humans. The Schizosaccharomyces pombe strain lacking the dss1{sup +} gene ({delta}dss1) shows a temperature-sensitive growth defect and accumulation of bulk poly(A){sup +} RNA in the nucleus at a nonpermissive temperature. In situ hybridization using probes for several specific mRNAs, however, revealed that the analyzed mRNAs were exported normally to the cytoplasm in {delta}dss1, suggesting that Dss1p is required for export of some subsets of mRNAs. We identified the pad1{sup +} gene, which encodes a component of the 26S proteasome, as a suppressor for the ts{sup -} phenotype of {delta}dss1. Unexpectedly, overexpression of Pad1p could suppress neither the defect in nuclear mRNA export nor a defect in proteasome function. In addition, loss of proteasome functions does not cause defective nuclear mRNA export. Dss1p seems to be a multifunctional protein involved in nuclear export of specific sets of mRNAs and the ubiquitin-proteasome pathway in fission yeast.

  13. Mutation of a C-Terminal Motif Affects Kaposi's Sarcoma-Associated Herpesvirus ORF57 RNA Binding, Nuclear Trafficking, and Multimerization ▿

    PubMed Central

    Taylor, Adam; Jackson, Brian R.; Noerenberg, Marko; Hughes, David J.; Boyne, James R.; Verow, Mark; Harris, Mark; Whitehouse, Adrian

    2011-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is essential for virus lytic replication. ORF57 regulates virus gene expression at multiple levels, enhancing transcription, stability, nuclear export, and translation of viral transcripts. To enhance the nuclear export of viral intronless transcripts, ORF57 (i) binds viral intronless mRNAs, (ii) shuttles between the nucleus, nucleolus, and the cytoplasm, and (iii) interacts with multiple cellular nuclear export proteins to access the TAP-mediated nuclear export pathway. We investigated the implications on the subcellular trafficking, cellular nuclear export factor recruitment, and ultimately nuclear mRNA export of an ORF57 protein unable to bind RNA. We observed that mutation of a carboxy-terminal RGG motif, which prevents RNA binding, affects the subcellular localization and nuclear trafficking of the ORF57 protein, suggesting that it forms subnuclear aggregates. Further analysis of the mutant shows that although it still retains the ability to interact with cellular nuclear export proteins, it is unable to export viral intronless mRNAs from the nucleus. Moreover, computational molecular modeling and biochemical studies suggest that, unlike the wild-type protein, this mutant is unable to self-associate. Therefore, these results suggest the mutation of a carboxy-terminal RGG motif affects ORF57 RNA binding, nuclear trafficking, and multimerization. PMID:21593148

  14. Theoretical nuclear physics. Final report

    SciTech Connect

    1997-05-01

    As the three-year period FY93-FY96 ended, there were six senior investigators on the grant full-time: Bulgac, Henley, Miller, Savage, van Kolck and Wilets. This represents an increase of two members from the previous three-year period, achieved with only a two percent increase over the budget for FY90-FY93. In addition, the permanent staff of the Institute for Nuclear Theory (George Bertsch, Wick Haxton, and David Kaplan) continued to be intimately associated with our physics research efforts. Aurel Bulgac joined the Group in September, 1993 as an assistant professor, with promotion requested by the Department and College of Arts and Sciences by September, 1997. Martin Savage, who was at Carnegie-Mellon University, jointed the Physics Department in September, 1996. U. van Kolck continued as research assistant professor, and we were supporting one postdoctoral research associate, Vesteinn Thorssen, who joined us in September, 1995. Seven graduate students were being supported by the Grant (Chuan-Tsung Chan, Michael Fosmire, William Hazelton, Jon Karakowski, Jeffrey Thompson, James Walden and Mitchell Watrous).

  15. Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

    PubMed Central

    Neems, Daniel S.; Garza-Gongora, Arturo G.; Smith, Erica D.; Kosak, Steven T.

    2016-01-01

    The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineage-enriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation. PMID:26957603

  16. Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis.

    PubMed

    Neems, Daniel S; Garza-Gongora, Arturo G; Smith, Erica D; Kosak, Steven T

    2016-03-22

    The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineage-enriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation. PMID:26957603

  17. Thallium-205 nuclear magnetic resonance study of the thallium(I)-gramicidin A association in trifluoroethanol

    SciTech Connect

    Turner, G.L.; Hinton, J.F.; Millett, F.S.

    1982-02-16

    Association of the thallous ion with gramicidin in 2,2,2-trifluoroethanol has been investigated by thallium-205 NMR spectroscopy. The data obtained suggest that the gramicidin dimer has two strong binding sites and one or more weak binding sites. Association constants for the strong binding sites were found to have the same value. From the temperature dependence of the strong binding site association constants, values for the association enthalpy and entropy of -2.13 +/- 0.12 kcal/mol and +5.45 +/- 0.04 eu, respectively, were obtained.

  18. Structural protein 4.1R is integrally involved in nuclear envelope protein localization, centrosome–nucleus association and transcriptional signaling

    PubMed Central

    Meyer, Adam J.; Almendrala, Donna K.; Go, Minjoung M.; Krauss, Sharon Wald

    2011-01-01

    The multifunctional structural protein 4.1R is required for assembly and maintenance of functional nuclei but its nuclear roles are unidentified. 4.1R localizes within nuclei, at the nuclear envelope, and in cytoplasm. Here we show that 4.1R, the nuclear envelope protein emerin and the intermediate filament protein lamin A/C co-immunoprecipitate, and that 4.1R-specific depletion in human cells by RNA interference produces nuclear dysmorphology and selective mislocalization of proteins from several nuclear subcompartments. Such 4.1R-deficiency causes emerin to partially redistribute into the cytoplasm, whereas lamin A/C is disorganized at nuclear rims and displaced from nucleoplasmic foci. The nuclear envelope protein MAN1, nuclear pore proteins Tpr and Nup62, and nucleoplasmic proteins NuMA and LAP2α also have aberrant distributions, but lamin B and LAP2β have normal localizations. 4.1R-deficient mouse embryonic fibroblasts show a similar phenotype. We determined the functional effects of 4.1R-deficiency that reflect disruption of the association of 4.1R with emerin and A-type lamin: increased nucleus–centrosome distances, increased β-catenin signaling, and relocalization of β-catenin from the plasma membrane to the nucleus. Furthermore, emerin- and lamin-A/C-null cells have decreased nuclear 4.1R. Our data provide evidence that 4.1R has important functional interactions with emerin and A-type lamin that impact upon nuclear architecture, centrosome–nuclear envelope association and the regulation of β-catenin transcriptional co-activator activity that is dependent on β-catenin nuclear export. PMID:21486941

  19. Health and Safety Considerations Associated with Sodium-Cooled Experimental Nuclear Fuel Dismantlement

    SciTech Connect

    Carvo, Alan E.

    2015-04-01

    Between the mid-1970s and the mid-1980s Sandia National Laboratory constructed eleven experimental assemblies to simulate debris beds formed in a sodium-cooled fast breeder reactor. All but one of the assemblies were irradiated. The experimental assemblies were transferred to the Idaho National Laboratory (INL) in 2007 and 2008 for storage, dismantlement, recovery of the uranium for reuse in the nuclear fuel cycle, and disposal of unneeded materials. This paper addresses the effort to dismantle the assemblies down to the primary containment vessel and repackage them for temporary storage until such time as equipment necessary for sodium separation is in place.

  20. CACTIN is an essential nuclear protein in Arabidopsis and may be associated with the eukaryotic spliceosome.

    PubMed

    Baldwin, Katherine L; Dinh, Elizabeth M; Hart, Brian M; Masson, Patrick H

    2013-04-01

    CACTIN is a conserved eukaryotic protein without known functional domains. Previous research revealed that CACTIN is essential in animals and protists and that it may function in inflammation pathways in animals; however, these pathways are not as broadly conserved as CACTIN. Therefore, the ancestral molecular function of CACTIN remains unknown. Our studies using Arabidopsis show that CACTIN is required for embryogenesis. Fluorescently tagged CACTIN localizes to nuclear speckles and colocalizes with known splicing proteins. In yeast-two-hybrid studies, we found that CACTIN binds to a putative component of the spliceosome. These findings support a possible role for CACTIN in splicing.

  1. Mutations in the Hepatocyte Nuclear Factor-1β Gene Are Associated with Familial Hypoplastic Glomerulocystic Kidney Disease

    PubMed Central

    Bingham, Coralie; Bulman, Michael P.; Ellard, Sian; Allen, Lisa I. S.; Lipkin, Graham W.; Hoff, William G. van't; Woolf, Adrian S.; Rizzoni, Gianfranco; Novelli, Giuseppe; Nicholls, Anthony J.; Hattersley, Andrew T.

    2001-01-01

    Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)–1β have been associated with early-onset diabetes and nondiabetic renal disease—particularly renal cystic disease. We investigated a possible role for the HNF-1β gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1β gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1β mutations. PMID:11085914

  2. Association between VDR and ESR1 gene polymorphisms with bone and obesity phenotypes in Chinese male nuclear families

    PubMed Central

    Gu, Jie-mei; Xiao, Wen-jin; He, Jin-wei; Zhang, Hao; Hu, Wei-wei; Hu, Yun-qiu; Li, Miao; Liu, Yu-juan; Fu, Wen-zhen; Yu, Jin-bo; Gao, Gao; Yue, Hua; Ke, Yao-hua; Zhang, Zhen-lin

    2009-01-01

    Aim: The goal of this study was to determine whether polymorphisms in the vitamin D receptor (VDR) and estrogen receptor alpha (ESR1) genes are associated with variations of peak bone mineral density (BMD) and obesity phenotypes in young Chinese men. Methods: A total of 1215 subjects from 400 Chinese nuclear families were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific multiple PCR (ASM-PCR) analysis at the ApaI, FokI, and CDX2 sites in the VDR gene and the PvuII and XbaI sites in the ESR1 gene. BMD at the lumbar spine and hip, total fat mass, and total lean mass were measured using dual energy X-ray absorptiometry. The associations between VDR and ESR1 gene polymorphisms with peak BMD, body mass index (BMI), total fat mass, total lean mass, and percentage fat mass (PFM) were determined using quantitative transmission disequilibrium tests (QTDTs). Results: Using QTDTs, no significant within-family associations were obtained between genotypes or haplotypes of the VDR and ESR1 genes and peak BMD. For the obesity phenotypes, the within-family associations were significant between CDX2 genotypes and BMI (P=0.046), fat mass (P=0.004), and PFM (P=0.020). Further, PvuII was significantly associated with the variation of fat mass and PFM (P=0.002 and P=0.039, respectively). A subsequent 1000 permutations were in agreement with these within-family association results. Conclusion: Our findings showed that VDR and ESR1 polymorphisms were associated with total fat mass in young Chinese men, but we failed to find a significant association between VDR and ESR1 genotypes and peak BMD. These findings suggested that the VDR and ESR1 genes are quantitative trait loci (QTL) underlying fat mass variation in young Chinese men. PMID:19960008

  3. Remedial investigation/feasibility study for the David Witherspoon, Inc., 901 Site, Knoxville, Tennessee: Volume 2, Appendixes

    SciTech Connect

    1996-10-01

    This document contains the appendixes for the remedial investigation and feasibility study for the David Witherspoon, Inc., 901 site in Knoxville, Tennessee. The following topics are covered in the appendixes: (A) David Witherspoon, Inc., 901 Site Historical Data, (B) Fieldwork Plans for the David Witherspoon, Inc., 901 Site, (C) Risk Assessment, (D) Remediation Technology Discussion, (E) Engineering Support Documentation, (F) Applicable or Relevant and Appropriate Requirements, and (G) Cost Estimate Documentation.

  4. Characterization of organic matter/ minerals associations in oilfield rocks using the nuclear microprobe

    NASA Astrophysics Data System (ADS)

    Mercier, F.; Toulhoat, N.; Trocellier, P.; Durand, C.

    1994-03-01

    The improvement of the oil production forecast and the recovery strategy is closely related to a better understanding of the oil reservoir wettability. As there is a need of a description of the spatial distribution of wettability down to the pore scale, new tools allow to enhance very fine scale wettability contrasts and to evidence the importance of mineralogy. Among them, we propose to use the nuclear microprobe analysis (NMA) for the qualitative and quantitative study of the organic matter/mineral interactions i.e. the description of the reservoir rock wettability. NMA, field emission SEM and AFM techniques are used to image and study the mechanisms and kinetics of the sorption of the organic matter on model samples: the organic film thicknesses and the major elemental contents (carbon and nitrogen) are measured.

  5. Panel report on coupled thermo-mechanical-hydro-chemical processes associated with a nuclear waste repository

    SciTech Connect

    Tsang, C.F.; Mangold, D.C.

    1984-07-01

    Four basic physical processes, thermal, hydrological, mechanical and chemical, are likely to occur in 11 different types of coupling during the service life of an underground nuclear waste repository. A great number of coupled processes with various degrees of importance for geological repositories were identified and arranged into these 11 types. A qualitative description of these processes and a tentative evaluation of their significance and the degree of uncertainty in prediction is given. Suggestions for methods of investigation generally include, besides theoretical work, laboratory and large scale field testing. Great efforts of a multidisciplinary nature are needed to elucidate details of several coupled processes under different temperature conditions in different geological formations. It was suggested that by limiting the maximum temperature to 100{sup 0}C in the backfill and in the host rock during the whole service life of the repository the uncertainties in prediction of long-term repository behavior might be considerably reduced.

  6. Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families

    PubMed Central

    Xu, X.-H.; Xiong, D.-H.; Liu, X.-G.; Guo, Y.; Chen, Y.; Zhao, J.; Recker, R. R.; Deng, H.-W.

    2010-01-01

    Summary This study was conducted to test whether there exists an association between vitamin D-binding protein (DBP) gene and compression strength index (CSI) phenotype. Candidate gene association analyses were conducted in total sample, male subgroup, and female subgroup, respectively. Two single-nucleotide polymorphisms (SNPs) with significant association results were found in males, suggesting the importance of DBP gene polymorphisms on the variation in CSI especially in Caucasian males. Introduction CSI of the femoral neck (FN) is a newly developed phenotype integrating information about bone size, body size, and bone mineral density. It is considered to have the potential to improve the performance of risk assessment for hip fractures because it is based on a combination of phenotypic traits influencing hip fractures rather than a single trait. CSI is under moderate genetic determination (with a heritability of ~44% found in this study), but the relevant genetic study is still rather scarce. Methods Based on the known physiological role of DBP in bone biology and the relatively high heritability of CSI, we tested 12 SNPs of the DBP gene for association with CSI variation in 405 Caucasian nuclear families comprising 1,873 subjects from the Midwestern US. Association analyses were performed in the total sample, male and female subgroups, respectively. Results Significant associations with CSI were found with two SNPs (rs222029, P=0.0019; rs222020, P=0.0042) for the male subgroup. Haplotype-based association tests corroborated the single-SNP results. Conclusions Our findings suggest that the DBP gene might be one of the genetic factors influencing CSI phenotype in Caucasians, especially in males. PMID:19543766

  7. Nuclear Translocation of β-Catenin during Mesenchymal Stem Cells Differentiation into Hepatocytes Is Associated with a Tumoral Phenotype

    PubMed Central

    Herencia, Carmen; Martínez-Moreno, Julio M.; Herrera, Concepción; Corrales, Fernando; Santiago-Mora, Raquel; Espejo, Isabel; Barco, Monserrat; Almadén, Yolanda; de la Mata, Manuel; Rodríguez-Ariza, Antonio; Muñoz-Castañeda, Juan R.

    2012-01-01

    Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype. PMID:22506042

  8. Nuclear translocation of β-catenin during mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype.

    PubMed

    Herencia, Carmen; Martínez-Moreno, Julio M; Herrera, Concepción; Corrales, Fernando; Santiago-Mora, Raquel; Espejo, Isabel; Barco, Monserrat; Almadén, Yolanda; de la Mata, Manuel; Rodríguez-Ariza, Antonio; Muñoz-Castañeda, Juan R

    2012-01-01

    Wnt/β-catenin pathway controls biochemical processes related to cell differentiation. In committed cells the alteration of this pathway has been associated with tumors as hepatocellular carcinoma or hepatoblastoma. The present study evaluated the role of Wnt/β-catenin activation during human mesenchymal stem cells differentiation into hepatocytes. The differentiation to hepatocytes was achieved by the addition of two different conditioned media. In one of them, β-catenin nuclear translocation, up-regulation of genes related to the Wnt/β-catenin pathway, such as Lrp5 and Fzd3, as well as the oncogenes c-myc and p53 were observed. While in the other protocol there was a Wnt/β-catenin inactivation. Hepatocytes with nuclear translocation of β-catenin also had abnormal cellular proliferation, and expressed membrane proteins involved in hepatocellular carcinoma, metastatic behavior and cancer stem cells. Further, these cells had also increased auto-renewal capability as shown in spheroids formation assay. Comparison of both differentiation protocols by 2D-DIGE proteomic analysis revealed differential expression of 11 proteins with altered expression in hepatocellular carcinoma. Cathepsin B and D, adenine phosphoribosyltransferase, triosephosphate isomerase, inorganic pyrophosphatase, peptidyl-prolyl cis-trans isomerase A or lactate dehydrogenase β-chain were up-regulated only with the protocol associated with Wnt signaling activation while other proteins involved in tumor suppression, such as transgelin or tropomyosin β-chain were down-regulated in this protocol. In conclusion, our results suggest that activation of the Wnt/β-catenin pathway during human mesenchymal stem cells differentiation into hepatocytes is associated with a tumoral phenotype.

  9. Nuclear weapons, nuclear effects, nuclear war

    SciTech Connect

    Bing, G.F.

    1991-08-20

    This paper provides a brief and mostly non-technical description of the militarily important features of nuclear weapons, of the physical phenomena associated with individual explosions, and of the expected or possible results of the use of many weapons in a nuclear war. Most emphasis is on the effects of so-called ``strategic exchanges.``

  10. Characterization of a nuclear localization signal in the C-terminus of the adeno-associated virus Rep68/78 proteins

    SciTech Connect

    Cassell, Geoffrey D.; Weitzman, Matthew D. . E-mail: weitzman@salk.edu

    2004-10-01

    Adeno-associated virus (AAV) replicates in the nucleus of infected cells, and therefore multiple nuclear import events are required for productive infection. We analyzed nuclear import of the viral Rep proteins and characterized a nuclear localization signal (NLS) in the C-terminus. We demonstrate that basic residues in this region constitute an NLS that is transferable and mediates interaction with the nuclear import receptor importin {alpha} in vitro. Mutant Rep proteins are predominantly cytoplasmic and are severely compromised for interactions with importin {alpha}, but retain their enzymatic functions in vitro. Interestingly, mutations of the NLS had significantly less effect on importin {alpha} interaction and replication in the context of Rep78 than when incorporated into the Rep68 protein. Together, our results demonstrate that a bipartite NLS exists in the shared part of Rep68 and Rep78, and suggest that an alternate entry mechanism may also contribute to nuclear localization of the Rep78 protein.

  11. Association of nuclear and mitochondrial genes with audiological examinations in Iranian patients with nonaminoglycoside antibiotics-induced hearing loss.

    PubMed

    Balali, Maryam; Kamalidehghan, Behnam; Farhadi, Mohammad; Ahmadipour, Fatemeh; Ashkezari, Mahmoud Dehghani; Hemami, Mohsen Rezaei; Arabzadeh, Hossein; Falah, Masoumeh; Meng, Goh Yong; Houshmand, Massoud

    2016-01-01

    Mitochondrial DNA mutations play an important role in causing sensorineural hearing loss. The purpose of this study was to determine the association of the mitochondrial genes RNR1, MT-TL1, and ND1 as well as the nuclear genes GJB2 and GJB6 with audiological examinations in nonfamilial Iranians with cochlear implants, using polymerase chain reaction, DNA sequencing, and RNA secondary structure analysis. We found that there were no novel mutations in the mitochondrial gene 12S rRNA (MT-RNR1) in patients with and without GJB2 mutation (GJB2(+) and GJB2(-), respectively), but a total of six polymorphisms were found. No mutations were observed in tRNA(Leu) (() (UUR) ()) (MT-TL1). Furthermore, eight polymorphisms were found in the mitochondrial ND1 gene. Additionally, no mutations were observed in the nuclear GJB6 gene in patients in the GJB2(-) and GJB2(+) groups. The speech intelligibility rating and category of auditory perception tests were statistically assessed in patients in the GJB2(-) and GJB2(+) groups. The results indicated that there was a significant difference (P<0.05) between the categories of auditory perception score in the GJB2(-) group compared to that in the GJB2(+) group. Successful cochlear implantation was observed among individuals with GJB2 mutations (GJB2(+)) and mitochondrial polymorphisms compared to those without GJB2 mutations (GJB2(-)). In conclusion, the outcome of this study suggests that variation in the mitochondrial and nuclear genes may influence the penetrance of deafness. Therefore, further genetic and functional studies are required to help patients in making the best choice for cochlear implants. PMID:26889084

  12. Association of nuclear and mitochondrial genes with audiological examinations in Iranian patients with nonaminoglycoside antibiotics-induced hearing loss

    PubMed Central

    Balali, Maryam; Kamalidehghan, Behnam; Farhadi, Mohammad; Ahmadipour, Fatemeh; Ashkezari, Mahmoud Dehghani; Hemami, Mohsen Rezaei; Arabzadeh, Hossein; Falah, Masoumeh; Meng, Goh Yong; Houshmand, Massoud

    2016-01-01

    Mitochondrial DNA mutations play an important role in causing sensorineural hearing loss. The purpose of this study was to determine the association of the mitochondrial genes RNR1, MT-TL1, and ND1 as well as the nuclear genes GJB2 and GJB6 with audiological examinations in nonfamilial Iranians with cochlear implants, using polymerase chain reaction, DNA sequencing, and RNA secondary structure analysis. We found that there were no novel mutations in the mitochondrial gene 12S rRNA (MT-RNR1) in patients with and without GJB2 mutation (GJB2+ and GJB2−, respectively), but a total of six polymorphisms were found. No mutations were observed in tRNALeu(UUR) (MT-TL1). Furthermore, eight polymorphisms were found in the mitochondrial ND1 gene. Additionally, no mutations were observed in the nuclear GJB6 gene in patients in the GJB2− and GJB2+ groups. The speech intelligibility rating and category of auditory perception tests were statistically assessed in patients in the GJB2− and GJB2+ groups. The results indicated that there was a significant difference (P<0.05) between the categories of auditory perception score in the GJB2− group compared to that in the GJB2+ group. Successful cochlear implantation was observed among individuals with GJB2 mutations (GJB2+) and mitochondrial polymorphisms compared to those without GJB2 mutations (GJB2−). In conclusion, the outcome of this study suggests that variation in the mitochondrial and nuclear genes may influence the penetrance of deafness. Therefore, further genetic and functional studies are required to help patients in making the best choice for cochlear implants. PMID:26889084

  13. Preliminary issues associated with the next generation nuclear plant intermediate heat exchanger design

    NASA Astrophysics Data System (ADS)

    Natesan, K.; Moisseytsev, A.; Majumdar, S.

    2009-07-01

    The Next Generation Nuclear Plant, with emphasis on production of both electricity and hydrogen, involves helium as the coolant and a closed-cycle gas turbine for power generation with a core outlet/gas turbine inlet temperature of 850-950 °C. In this concept, an intermediate heat exchanger is used to transfer the heat from primary helium from the core to the secondary fluid, which can be helium, a nitrogen/helium mixture, or a molten salt. This paper assesses the issues pertaining to shell-and-tube and compact heat exchangers. A detailed thermal-hydraulic analysis was performed to calculate heat transfer, temperature distribution, and pressure drop inside both printed circuit and shell-and-tube heat exchangers. The analysis included evaluation of the role of key process parameters, geometrical factors in heat exchanger designs, and material properties of structural alloys. Calculations were performed for helium-to-helium, helium-to-helium/nitrogen, and helium-to-salt heat exchangers.

  14. Geo-Space observation of atmospheric environmental effects associated with 2011 Fukushima nuclear accident

    NASA Astrophysics Data System (ADS)

    Pulinets, Sergey; Ouzounov, Dimitar; Hernandez-Pajares, Manuel; Hattori, Katsumi; Garcia-Rigo, Alberto

    2014-05-01

    Our approach of using multiple geo-space observation is based on the LAIC (Lithosphere- Atmosphere- Ionosphere Coupling) model and the gained experience during similar analysis of Three-Mile Island and Chernobyl accidents. We do collect a unique dataset of geophysical data for the period around the time of the most active phase of Fukushima explosions (from 12 March till 31 March, 71-90 DOY). We analyzed following data sets: (i) ground temperature and relative humidity data from the JMA network of Japan, (ii) satellite meteorological data and assimilative models to obtain the integrated water vapor chemical potential; (iii) the infrared emission on the top of atmosphere measured by NOAA and GEOS satellites estimated as Outgoing Longwave Radiation; and (iv) multiple ionospheric measurements , including ground based ionosondes, GPS vTEC from GEONET network, COSMIC/FORMOSAT constellation occultation data, JASON satellite TEC measurements, and tomography reconstruction technique to obtain 3D distribution of electron concentration around the Fukushima power plant. As a result we were able to detect the anomalies in different geophysical parameters representing the dynamics of the Fukushima nuclear accident development and the effects on the atmospheric environment. Their temporal evolution demonstrates the synergy in different atmospheric anomalies development what implies the existence of the common physical mechanism described by the LAIC model.

  15. Spatial location of indomethacin associated with unimeric amphiphilic carrier macromolecules as determined by nuclear magnetic resonance spectroscopy.

    PubMed

    Orban, David E; Moretti, Alysha; Uhrich, Kathryn E

    2016-07-01

    A combination of nuclear magnetic resonance (NMR) techniques including, proton NMR, relaxation analysis, two-dimensional nuclear Overhauser effect spectroscopy, and diffusion-ordered spectroscopy, has been used to demonstrate the spatial location of indomethacin within a unimolecular micelle. Understanding the location of drugs within carrier molecules using such NMR techniques can facilitate rational carrier design. In addition, this information provides insight to encapsulation efficiency of different drugs to determine the most efficient system for a particular bioactive. This study demonstrates that drugs loaded by the unimolecular amphiphile under investigation are not necessarily encapsulated but reside or localize to the periphery or interfacial region of the carrier molecule. The results have further implications as to the features of the unimolecular carrier that contribute to drug loading. In addition, evidence of drug retention associated with the unimolecular surfactant is possible in organic media, as well as in an aqueous environment. Such findings have implications for rational carrier design to correlate the carrier features to the drug of interest and indicate the strong retention capabilities of the unimolecular micelle for delivery applications. Copyright © 2016 John Wiley & Sons, Ltd.

  16. Serine 62-Phosphorylated MYC Associates with Nuclear Lamins and Its Regulation by CIP2A Is Essential for Regenerative Proliferation.

    PubMed

    Myant, Kevin; Qiao, Xi; Halonen, Tuuli; Come, Christophe; Laine, Anni; Janghorban, Mahnaz; Partanen, Johanna I; Cassidy, John; Ogg, Erinn-Lee; Cammareri, Patrizia; Laiterä, Tiina; Okkeri, Juha; Klefström, Juha; Sears, Rosalie C; Sansom, Owen J; Westermarck, Jukka

    2015-08-11

    An understanding of the mechanisms determining MYC's transcriptional and proliferation-promoting activities in vivo could facilitate approaches for MYC targeting. However, post-translational mechanisms that control MYC function in vivo are poorly understood. Here, we demonstrate that MYC phosphorylation at serine 62 enhances MYC accumulation on Lamin A/C-associated nuclear structures and that the protein phosphatase 2A (PP2A) inhibitor protein CIP2A is required for this process. CIP2A is also critical for serum-induced MYC phosphorylation and for MYC-elicited proliferation induction in vitro. Complementary transgenic approaches and an intestinal regeneration model further demonstrated the in vivo importance of CIP2A and serine 62 phosphorylation for MYC activity upon DNA damage. However, targeting of CIP2A did not influence the normal function of intestinal crypt cells. These data underline the importance of nuclear organization in the regulation of MYC phosphorylation, leading to an in vivo demonstration of a strategy for inhibiting MYC activity without detrimental physiological effects.

  17. A tribute to Charles David Kelman MD: ophthalmologist, inventor and pioneer of phacoemulsification surgery.

    PubMed

    Pandey, Suresh K; Milverton, E John; Maloof, Anthony J

    2004-10-01

    Charles David Kelman was born in Brooklyn, New York, USA, on 23 May 1930 and passed away in Boca Raton, Florida, USA, on 1 June 2004 at the age of 74 years after a long battle with cancer. He received a Bachelor of Science degree from Tufts University in 1950 and completed medical studies at the University of Geneva, Switzerland, in 1956. He was Clinical Professor of Ophthalmology at New York Medical College and an Attending Surgeon at New York Eye and Ear Infirmary and Manhattan Eye, Ear and Throat Hospital. Although a prolific inventor, he will be best remembered for developing phacoemulsification, following his realization while sitting in a dentist's chair, that ultrasonic vibrations could be used to emulsify the aged crystalline lens through a very small incision. His pioneering work revolutionized cataract surgery. He also pioneered cryo-extraction of cataracts, the use of freezing for the repair of retinal detachments and designed numerous ophthalmic instruments and intraocular lenses. Dr Kelman received numerous awards, including the American Academy of Ophthalmology Achievement Award (1970), the Ridley Medal from the International Congress of Ophthalmology (1990), and the Inventor of the Year Award from The New York Patent, Trademark and Copyright Law Association (1992). Most recently (2003), Dr Kelman was honoured by the American Academy of Ophthalmology with the Laureate Recognition award. Dr Kelman was also an accomplished Broadway producer, composer and jazz saxophonist. With his demise, the ophthalmic and medical community lost a famed inventor with multifaceted talents and one of the great ophthalmologists of the twentieth century.

  18. Preliminary issues associated with the next generation nuclear plant intermediate heat exchanger design.

    SciTech Connect

    Natesan, K.; Moisseytsev, A.; Majumdar, S.; Shankar, P. S.; Nuclear Engineering Division

    2007-04-05

    The Next Generation Nuclear Plant (NGNP), which is an advanced high temperature gas reactor (HTGR) concept with emphasis on production of both electricity and hydrogen, involves helium as the coolant and a closed-cycle gas turbine for power generation with a core outlet/gas turbine inlet temperature of 900-1000 C. In the indirect cycle system, an intermediate heat exchanger is used to transfer the heat from primary helium from the core to the secondary fluid, which can be helium, nitrogen/helium mixture, or a molten salt. The system concept for the vary high temperature reactor (VHTR) can be a reactor based on the prismatic block of the GT-MHR developed by a consortium led by General Atomics in the U.S. or based on the PBMR design developed by ESKOM of South Africa and British Nuclear Fuels of U.K. This report has made a preliminary assessment on the issues pertaining to the intermediate heat exchanger (IHX) for the NGNP. Two IHX designs namely, shell and tube and compact heat exchangers were considered in the assessment. Printed circuit heat exchanger, among various compact heat exchanger (HX) designs, was selected for the analysis. Irrespective of the design, the material considerations for the construction of the HX are essentially similar, except may be in the fabrication of the units. As a result, we have reviewed in detail the available information on material property data relevant for the construction of HX and made a preliminary assessment of several relevant factors to make a judicious selection of the material for the IHX. The assessment included four primary candidate alloys namely, Alloy 617 (UNS N06617), Alloy 230 (UNS N06230), Alloy 800H (UNS N08810), and Alloy X (UNS N06002) for the IHX. Some of the factors addressed in this report are the tensile, creep, fatigue, creep fatigue, toughness properties for the candidate alloys, thermal aging effects on the mechanical properties, American Society of Mechanical Engineers (ASME) Code compliance

  19. The association betweeen cancers and low level radiation: An evaluation of the epidemiological evidence at the Hanford Nuclear Weapons Facility

    SciTech Connect

    Britton, J. |

    1993-05-01

    Cancer has traditionally been linked to exposure to high doses of radiation, but there is considerable controversy regarding the carcinogenicity of low doses of ionizing radiation in humans. Over the past 30 years there have been 14 studies conducted on employees at the Hanford nuclear weapons facility to investigate the relationship between exposure to low doses of radiation and mortality due to cancer (1-14). Interest in this issue was originally stimulated by the Atomic Energy Commission (AEC) which was trying to determine whether the linear extrapolation of health effects from high to low dose exposure was accurate. If the risk has been underestimated, then the maximum permissible occupational radiation exposure in the United States had been set too high. Because the health risk associated with low level radiation are unclear and controversial it seems appropriate to review the studies relating to Hanford at this time.

  20. Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection.

    PubMed

    Newkirk, M M; van Venrooij, W J; Marshall, G S

    2001-01-01

    The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood. We present evidence that healthy individuals with cytomegalovirus (CMV) infection have an increased frequency and quantity of antibodies to ribonucleoprotein, directed primarily against the U1-70k protein. A significant association between the presence of antibodies to CMV and antibodies to the total RNP targeted by the immune response to the spliceosome (to both the Sm and RNP; Sm/RNP) was found for patients with systemic lupus erythematosus (SLE) but not those with mixed connective-tissue disease. CMV thus may play a role in inducing autoimmune responses in a subset of patients with systemic lupus erythematosus.

  1. Autoimmune response to U1 small nuclear ribonucleoprotein (U1 snRNP) associated with cytomegalovirus infection.

    PubMed

    Newkirk, M M; van Venrooij, W J; Marshall, G S

    2001-01-01

    The induction of autoantibodies to U1 small nuclear ribonucleoprotein (U1 snRNP) complexes is not well understood. We present evidence that healthy individuals with cytomegalovirus (CMV) infection have an increased frequency and quantity of antibodies to ribonucleoprotein, directed primarily against the U1-70k protein. A significant association between the presence of antibodies to CMV and antibodies to the total RNP targeted by the immune response to the spliceosome (to both the Sm and RNP; Sm/RNP) was found for patients with systemic lupus erythematosus (SLE) but not those with mixed connective-tissue disease. CMV thus may play a role in inducing autoimmune responses in a subset of patients with systemic lupus erythematosus. PMID:11438044

  2. Emotion reactivity and regulation are associated with psychological functioning following the 2011 earthquake, tsunami, and nuclear crisis in Japan.

    PubMed

    Cavanagh, Sarah R; Fitzgerald, Erin J; Urry, Heather L

    2014-04-01

    Frequent and successful use of cognitive reappraisal, an emotion regulation strategy that involves rethinking the meaning of an emotional event in order to change one's emotional response, has been linked in everyday life to positive outcomes such as higher well-being. Whether we should expect this association to be maintained in a strong, temporally and spatially close emotional context is an unexplored question that might have important implications for our understanding of emotion regulation and its relations to psychological functioning. In this study of members of the U. S. Embassy Tokyo community in the months following the March 2011 earthquake, tsunami, and nuclear crisis in Japan, self-reported use of cognitive reappraisal was not related to psychological functioning, but demonstrated success using cognitive reappraisal to decrease feelings of unpleasantness in response to disaster-related pictures on a performance-based task was associated with fewer symptoms of depression and posttraumatic stress. Moreover, emotional reactivity to these pictures was associated with greater symptomatology. These results suggest that situational intensity may be an important moderator of reappraisal and psychological functioning relationships.

  3. Prolonged induced hypothermia in hemorrhagic shock is associated with decreased muscle metabolism: a nuclear magnetic resonance-based metabolomics study.

    PubMed

    Lusczek, Elizabeth R; Lexcen, Daniel R; Witowski, Nancy E; Determan, Charles; Mulier, Kristine E; Beilman, Greg

    2014-01-01

    Hemorrhagic shock is a leading cause of trauma-related death in war and is associated with significant alterations in metabolism. Using archived serum samples from a previous study, the purpose of this work was to identify metabolic changes associated with induced hypothermia in a porcine model of hemorrhagic shock. Twelve Yorkshire pigs underwent a standardized hemorrhagic shock and resuscitation protocol to simulate battlefield injury with prolonged evacuation to definitive care in cold environments. Animals were randomized to receive either hypothermic (33°C) or normothermic (39°C) limited resuscitation for 8 h, followed by standard resuscitation. Proton nuclear magnetic resonance spectroscopy was used to evaluate serum metabolites from these animals at intervals throughout the hypothermic resuscitation period. Animals in the hypothermic group had a significantly higher survival rate (P = 0.02) than normothermic animals. Using random forest analysis, a difference in metabolic response between hypothermic and normothermic animals was identified. Hypothermic resuscitation was characterized by decreased concentrations of several muscle-related metabolites including taurine, creatine, creatinine, and amino acids. This study suggests that a decrease in muscle metabolism as a result of induced hypothermia is associated with improved survival. PMID:24052038

  4. Prolonged induced hypothermia in hemorrhagic shock is associated with decreased muscle metabolism: a nuclear magnetic resonance-based metabolomics study.

    PubMed

    Lusczek, Elizabeth R; Lexcen, Daniel R; Witowski, Nancy E; Determan, Charles; Mulier, Kristine E; Beilman, Greg

    2014-01-01

    Hemorrhagic shock is a leading cause of trauma-related death in war and is associated with significant alterations in metabolism. Using archived serum samples from a previous study, the purpose of this work was to identify metabolic changes associated with induced hypothermia in a porcine model of hemorrhagic shock. Twelve Yorkshire pigs underwent a standardized hemorrhagic shock and resuscitation protocol to simulate battlefield injury with prolonged evacuation to definitive care in cold environments. Animals were randomized to receive either hypothermic (33°C) or normothermic (39°C) limited resuscitation for 8 h, followed by standard resuscitation. Proton nuclear magnetic resonance spectroscopy was used to evaluate serum metabolites from these animals at intervals throughout the hypothermic resuscitation period. Animals in the hypothermic group had a significantly higher survival rate (P = 0.02) than normothermic animals. Using random forest analysis, a difference in metabolic response between hypothermic and normothermic animals was identified. Hypothermic resuscitation was characterized by decreased concentrations of several muscle-related metabolites including taurine, creatine, creatinine, and amino acids. This study suggests that a decrease in muscle metabolism as a result of induced hypothermia is associated with improved survival.

  5. Emotion reactivity and regulation are associated with psychological functioning following the 2011 earthquake, tsunami, and nuclear crisis in Japan.

    PubMed

    Cavanagh, Sarah R; Fitzgerald, Erin J; Urry, Heather L

    2014-04-01

    Frequent and successful use of cognitive reappraisal, an emotion regulation strategy that involves rethinking the meaning of an emotional event in order to change one's emotional response, has been linked in everyday life to positive outcomes such as higher well-being. Whether we should expect this association to be maintained in a strong, temporally and spatially close emotional context is an unexplored question that might have important implications for our understanding of emotion regulation and its relations to psychological functioning. In this study of members of the U. S. Embassy Tokyo community in the months following the March 2011 earthquake, tsunami, and nuclear crisis in Japan, self-reported use of cognitive reappraisal was not related to psychological functioning, but demonstrated success using cognitive reappraisal to decrease feelings of unpleasantness in response to disaster-related pictures on a performance-based task was associated with fewer symptoms of depression and posttraumatic stress. Moreover, emotional reactivity to these pictures was associated with greater symptomatology. These results suggest that situational intensity may be an important moderator of reappraisal and psychological functioning relationships. PMID:24708504

  6. CESAR5.3: An Industrial Tool for Nuclear Fuel and Waste Characterization with Associated Qualification - 12067

    SciTech Connect

    Vidal, Jean-Marc; Eschbach, Romain; Launay, Agnes; Binet, Christophe; THRO, Jean-Francois

    2012-07-01

    CEA and AREVA-NC have developed and used a depletion code named CESAR for 30 years. This user-friendly industrial tool provides fast characterizations for all types of nuclear fuel (PWR / UOX or MOX or reprocess Uranium, BWR / UOX or MOX, MTR and SFR) and the wastes associated. CESAR can evaluate 100 heavy nuclides, 200 fission products and 150 activation products (with Helium and Tritium formation). It can also characterize the structural material of the fuel (Zircalloy, stainless steel, M5 alloy). CESAR provides depletion calculations for any reactor irradiation history and from 3 months to 1 million years of cooling time. CESAR5.3 is based on the latest calculation schemes recommended by the CEA and on an international nuclear data base (JEFF-3.1.1). It is constantly checked against the CEA referenced and qualified depletion code DARWIN. CESAR incorporates the CEA qualification based on the dissolution analyses of fuel rod samples and the 'La Hague' reprocessing plant feedback experience. AREVA-NC uses CESAR intensively at 'La Hague' plant, not only for prospective studies but also for characterizations at different industrial facilities all along the reprocessing process and waste conditioning (near 150 000 calculations per year). CESAR is the reference code for AREVA-NC. CESAR is used directly or indirectly with other software, data bank or special equipment in many parts of the La Hague plants. The great flexibility of CESAR has rapidly interested other projects. CESAR became a 'tool' directly integrated in some other softwares. Finally, coupled with a Graphical User Interface, it can be easily used independently, responding to many needs for prospective studies as a support for nuclear facilities or transport. An English version is available. For the principal isotopes of U and Pu, CESAR5 benefits from the CEA experimental validation for the PWR UOX fuels, up to a burnup of 60 GWd/t and for PWR MOX fuels, up to 45 GWd/t. CESAR version 5.3 uses the CEA

  7. Nuclear-cytoplasmic conflict in pea (Pisum sativum L.) is associated with nuclear and plastidic candidate genes encoding acetyl-CoA carboxylase subunits.

    PubMed

    Bogdanova, Vera S; Zaytseva, Olga O; Mglinets, Anatoliy V; Shatskaya, Natalia V; Kosterin, Oleg E; Vasiliev, Gennadiy V

    2015-01-01

    In crosses of wild and cultivated peas (Pisum sativum L.), nuclear-cytoplasmic incompatibility frequently occurs manifested as decreased pollen fertility, male gametophyte lethality, sporophyte lethality. High-throughput sequencing of plastid genomes of one cultivated and four wild pea accessions differing in cross-compatibility was performed. Candidate genes for involvement in the nuclear-plastid conflict were searched in the reconstructed plastid genomes. In the annotated Medicago truncatula genome, nuclear candidate genes were searched in the portion syntenic to the pea chromosome region known to harbor a locus involved in the conflict. In the plastid genomes, a substantial variability of the accD locus represented by nucleotide substitutions and indels was found to correspond to the pattern of cross-compatibility among the accessions analyzed. Amino acid substitutions in the polypeptides encoded by the alleles of a nuclear locus, designated as Bccp3, with a complementary function to accD, fitted the compatibility pattern. The accD locus in the plastid genome encoding beta subunit of the carboxyltransferase of acetyl-coA carboxylase and the nuclear locus Bccp3 encoding biotin carboxyl carrier protein of the same multi-subunit enzyme were nominated as candidate genes for main contribution to nuclear-cytoplasmic incompatibility in peas. Existence of another nuclear locus involved in the accD-mediated conflict is hypothesized.

  8. Interview with David H. Jonassen: Looking at the Field of Educational Technology from Radical and Multiple Perspectives

    ERIC Educational Resources Information Center

    Simsek, Ali

    2012-01-01

    There are people whose names are identified with their fields. When an outsider wants to learn about the field of educational technology and enters some keywords, David H. Jonassen is perhaps one the few people whose names will appear instantly. Of course, this is not without reasons. David H. Jonassen has produced enormous amount of work…

  9. Commentary on "An Evolutionarily Informed Education Science" by David C. Geary

    ERIC Educational Resources Information Center

    Ellis, George F. R.

    2008-01-01

    Dr. David C. Geary's article centers on the concept of inherited folk psychology modules, together with the idea of a transition from primary to secondary learning. This article suggests that there exist only effective folk psychology modules, which are the result of interaction of inherited primary emotional systems with the physical, biological,…

  10. Astronaut David Wolf participates in training for contingency EVA in WETF

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Astronaut David A. Wolf participates in training for contingency extravehicular activity (EVA) for the STS-58 mission. The mission specialist was about to be submerged to a point of neutral buoyancy in the JSC Weightless Environment Training Facility (WETF). In this view, Wolf is aided by technicians in donning the gloves for his extravehicular mobility unit (EMU).

  11. Q & A with Ed Tech Leaders: Interview with David M. Monetti

    ERIC Educational Resources Information Center

    Fulgham, Susan M.; Shaughnessy, Michael F.

    2014-01-01

    Contributing editors Susan Fulgham and Michael Shaughnessy present their interview with David M. Monetti, Professor in the Department of Psychology and Counseling at Valdosta State University. Monetti teaches courses in educational psychology, learning, and measurement and evaluation. He is actively involved with the public schools as a researcher…

  12. Forging Futures with Teens and Science Fiction: A Conversation with Greg Bear and David Brin.

    ERIC Educational Resources Information Center

    Moltz, Sandy

    2003-01-01

    Presents an interview with Greg Bear and David Brin, two science fiction writers who started Reading for the Future, an international project geared toward secondary school students that shows teachers and librarians how science fiction inspires young readers. Discusses programs that have come out of this group; standards for books geared toward…

  13. Being "Stresslessly Invisible": The Rise and Fall of Videophony in David Foster Wallace's "Infinite Jest"

    ERIC Educational Resources Information Center

    Ribbat, Christoph

    2010-01-01

    In a satiric chapter of David Foster Wallace's novel "Infinite Jest," a mock media expert reports how American consumers of the near future recoil from a new communication device known as "videophony" and return to the voice-only telephone of the Bell Era. This article explores the said chapter in the framework of media theories reading the…

  14. The Camp David Ceremony and the Genre of the Presidential Parasocial Broadcast Announcement.

    ERIC Educational Resources Information Center

    Houser, William Evan

    In 1978, the historic Camp David Peace Accords between Egypt and Israel were signed in a ceremony broadcast from the White House. The ceremony may be seen as a member of a rhetorical genre informally called the Presidential Parasocial Broadcast Announcement, but with a new twist. The genre has its roots in the Fireside Chats of Franklin D.…

  15. Constructing the Path to Tomorrow: Strategic Planning and Implementation in the David Douglas School District.

    ERIC Educational Resources Information Center

    Cole, Richard

    Following a brief introduction to the David Douglas School District community and schools located in a partly unincorporated area of Portland/Multnomah County, Oregon, this publication describes the district's prior annual goal-setting process and its evolving Vision 90's strategic-planning and implementation process (SPI). Strategic-planning…

  16. Finding Our Way Back to Healthy Eating: A Conversation with David A. Kessler

    ERIC Educational Resources Information Center

    Azzam, Amy M.

    2009-01-01

    In this interview, David Kessler, former commissioner of the Food and Drug Administration, explains why so many people overeat. Changing lifestyles promote the constant availability of food and around-the-clock eating. In today's highly processed foods, food companies are able to dial in the exact amount of fat, sugar, and salt that will make…

  17. The Archives of the History of American Psychology: An Interview with David B. Baker.

    ERIC Educational Resources Information Center

    Prieto, Loreto R.

    2001-01-01

    Presents an interview with David B. Baker, Director of the Archives of the History of American Psychology. Covers topics such as: Baker's interest in the history of psychology, his work at the Archives of the History of American Psychology, and recommendations for teachers when addressing history in non-history courses. (CMK)

  18. Remapping Place and Narrative in Native American Literature: David Treuer's "The Hiawatha"

    ERIC Educational Resources Information Center

    Kirwan, Padraig

    2007-01-01

    David Treuer's 1997 novel, "The Hiawatha," engages the traditional literary strategies employed by Native American writing, compares those strategies to earlier narratives (Native American and canonically American), offers a reassessment of indigenous novelistic structures, engages critical responses to tribal fiction, and does so in response to…

  19. David Hume's Monetary Theory Revisited: Was He Really a Quantity Theorist and an Inflationist?

    ERIC Educational Resources Information Center

    Wennerlind, Carl

    2005-01-01

    David Hume's monetary theory has been controversial since its formulation. Lately, the focus has been on Hume's alleged misapplication of the quantity theory of money. While he appears to subscribe to a simple quantity theory with money neutrality, in a famously contested passage in the essay Of Money, he violates the neutrality condition by…

  20. Paul Voosen Receives 2013 David Perlman Award for Excellence in Science Journalism—News: Citation

    NASA Astrophysics Data System (ADS)

    Zaneski, Cyril T.

    2014-01-01

    It's my pleasure to nominate Paul Voosen, the former science reporter for Greenwire, for the David Perlman award. Last November, as Superstorm Sandy pounded the East Coast of the United States, Paul found himself stranded for several days in Miami, mourning a recently deceased family member.

  1. 76 FR 66995 - David T. Koon, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... practitioner whose state license has been suspended or revoked. David W. Wang, 72 FR 54297, 54298 (2007); Sheran Arden Yeates, 71 FR 39130, 39131 (2006); Dominick A. Ricci, 58 FR 51104, 51105 (1993); Bobby Watts, 53 FR 11919, 11920 (1988). See also 21 U.S.C. 824(a)(3) (authorizing the revocation of a...

  2. Children and Religious Education in an Age of Globalization: Learning from David Ng

    ERIC Educational Resources Information Center

    Mercer, Joyce Ann

    2002-01-01

    This article assesses David Ng's contribution to religious education with children. Ng offered practical strategies for full inclusion of children in faith communities. One limitation in Ng's work on children is its lack of attention to the role of culture, an unusual omission given his interest in multicultural religious education. This gap…

  3. David Dorfman's "Here": A Community-Building Approach in Dance Education

    ERIC Educational Resources Information Center

    Parrish, Mila

    2009-01-01

    Over a three-month period, Arcadia High School and Arizona State University formed a community partnership with the help of New York modern dance choreographer David Dorfman to create an original dance titled "Here." Dorfman's community-building approach is based on personal refection, collaboration, critical thinking, problem solving, genuine…

  4. Builders Challenge High Performance Builder Spotlight: David Weekley Homes, Houston, Texas

    SciTech Connect

    2009-12-22

    Building America Builders Challenge fact sheet on David Weekley Homes of Houston, Texas. The builder plans homes as a "system," with features such as wood-framed walls that are air-sealed then insulated with R-13 unfaced fiberglass batts plus an external covering of R-2 polyisocyanurate rigid foam sheathing.

  5. Henry David Thoreau: American Transcendentalism and the Implications for Rhetoric in American Civic Education.

    ERIC Educational Resources Information Center

    Grapsy, Ronald P., Jr.

    The American Philosopher Henry David Thoreau provides modern students an important perspective on the state and operation of democratic institutions and society. Many critics of his philosophy cite the author's inability to live up to his articulated tenets as grounds to dismiss the exhortative writings as idealistic and implausible. This essay…

  6. A Life in Research, an Adventure in Creativity: An Interview with David W. Chan

    ERIC Educational Resources Information Center

    Henshon, Suzanna E.

    2011-01-01

    This article presents an interview with David W. Chan, founding director of the Program for the Gifted and Talented at the Chinese University of Hong Kong. Chan has worked at the university for nearly 30 years, first in the Department of Psychiatry and then in the Department of Educational Psychology. Currently, he is also an adjunct professor of…

  7. David Maurice's contributions to optical ophthalmic instrumentation: roots of the scanning slit clinical confocal microscope.

    PubMed

    Masters, Barry R

    2004-03-01

    This paper explores the seminal contributions of David Maurice to the field of ophthalmic instrumentation. His development of the specular microscope, the scanning slit optical confocal microscope, and the corneal microfluorometer resulted in advances in our understanding of corneal morphology, physiology, and pathology. The development of the scanning slit, clinical confocal microscope is not a new paradigm or a paradigm shift, but a continuous series of interlinked technical advances from the early work of Vogt to Thaer's development of a clinical confocal microscope. For each instrument both the connection to the prior work of others and the unique advances are discussed and contrasted. This paper develops the connections and parallel developments in the instrument developments of Goldmann, Maurice, Svishchev, Baer, Koester, Masters, and Thaer. The evidence in support of the thesis consists of published papers, patents, personal communication, and study of Goldmann's book collection in Bern. A second theme is that knowledge of physics is a prerequisite for optical instrument development in ophthalmology. David Maurice had a university degree in physics and Hans Goldmann learned physics from his books. The contributions of David Maurice to optical instrumentation follow the major contributions of Goldmann and facilitated and stimulated other scientists who acknowledged their important intellectual debt to David Maurice.

  8. Improving the Quality of the Teaching Force: A Conversation with David C. Berliner.

    ERIC Educational Resources Information Center

    Scherer, Marge

    2001-01-01

    In a question-and-answer session, David C. Berliner discusses wide range of topics related to current state of the teaching profession, including qualities of the expert teacher, attracting higher quality teachers, teacher career-stage programs, merit pay, and promising reforms for teacher education in last decade. (PKP)

  9. 76 FR 39865 - Mr. David Creasey; Notice of Availability of Environmental Assessment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... regulations, 18 CFR Part 380 (Order No. 486, 52 FR 47897), the Office of Energy Projects has reviewed the... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Mr. David Creasey; Notice of Availability of Environmental Assessment...

  10. An Interview with David Rindskopf: A Leading Voice on Teaching Statistics and Methodology

    ERIC Educational Resources Information Center

    Bembenutty, Hefer

    2011-01-01

    This article presents an interview with David Rindskopf, a Distinguished Professor of Educational Psychology and Psychology at the City University of New York Graduate Center, where he has taught since 1979. His research and teaching are in the area of applied statistics, measurement, and research design. He is a fellow of the American Statistical…

  11. David Douglas Duncan's Changing Views on War: An Audio-Visual Presentation.

    ERIC Educational Resources Information Center

    Politowski, Richard

    This paper is the script for a slide presentation about photographer David Douglas Duncan and his view of war. It is intended to be used with slides made from pictures Duncan took during World War II, the Korean War, and the war in Viet Nam and published in various books and periodicals. It discusses a shift in emphasis to be seen both in the…

  12. On a Theme by Rene David: Comparative Law as "Technique Indispensable."

    ERIC Educational Resources Information Center

    McAuley, Michael

    2002-01-01

    Explores a text by Rene David relating to the teaching of comparative law and the comparative teaching of law. Discusses bijural education as a way to comprehensively teach the civil and common law traditions. Addresses construction of a bijural curriculum and skills of comparative law teaching. (EV)

  13. Physics for Teachers: Understanding Physics: David Cassidy, Gerald Holton, & James Rutherford

    NASA Astrophysics Data System (ADS)

    Hubisz, John L.

    2009-11-01

    Physics for Teachers: Understanding Physics, by David Cassidy, Gerald Holton, & James Rutherford and published by Springer Verlag, New York, NY 10010 (2002), pp. xxiii + 851 80.00 hardback. ISBN 0-387-98756-8. Student Guide & Instructor Guide are also available. The text and Instructor Guide are available online at http://www.dcassidybooks.com/up.html

  14. Astronaut David Scott undergoes water egress training in building 260A

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Astronaut David R. Scott, pilot of the Gemini 8 prime crew, undergoes water egress training in a special tank in building 260A at the Manned Spacecraft Center (MSC), Houston, Texas. An MSC swimmer assists in the training exercise. A boilerplate model of a Gemini spacecraft floats in water beside Scott.

  15. David Brearly: Soldier-Statesmen of the Constitution. A Bicentennial Series No. 18.

    ERIC Educational Resources Information Center

    Army Center of Military History, Washington, DC.

    David Brearly was a student of the Enlightenment philosophers and English jurists who taught that a contract existed between the individual and the state, and this exposure influenced him as a framer of the Constitution, with its careful definitions of the obligations of government and the rights of citizens. This booklet on Brearly is one in a…

  16. Education, Educational Research, and the "Grammar" of Understanding: A Response to David Bridges

    ERIC Educational Resources Information Center

    Smeyers, Paul

    2009-01-01

    This article is the author's response to a paper presented by David Bridges. Bridges' central question: "Is there something exclusive and superior about insider understanding which the outsider cannot understand?" is indeed not only crucial to the contexts he explicitly deals with, i.e. religious understanding, ethnographic research and…

  17. David Hurst Thomas and the Historical Archaeology of the Spanish Borderlands.

    ERIC Educational Resources Information Center

    Snead, James E.

    2000-01-01

    Discusses David Hurst Thomas' archaeological work on the Spanish borderlands, which integrates field archaeology and documentary history. Focuses on locating and studying the Santa Catalina de Guale. Addresses his project on the Pueblo San Marcos that will further test his ideas about the Spanish mission period. (CMK)

  18. David F. Treagust: Congenial Soul, Science Educator, and International Research Leader

    ERIC Educational Resources Information Center

    Tobin, Kenneth; Rennie, Leonie; Venville, Grady; Chu, Hye-Eun; Fensham, Peter; Gallagher, James; Duit, Reinders; Graeber, Wolfgang; van den Berg, Ed; Hand, Brian; Ritchie, Stephen; Dillon, Justin

    2011-01-01

    For almost a half century David F. Treagust has been an exemplary science educator who has contributed through his dedication and commitments to students, curriculum development and collaboration with teachers, and cutting edge research in science education that has impacted the field globally, nationally and locally. A hallmark of his outstanding…

  19. An Evaluation Of Family Life Education At David Thompson Secondary School.

    ERIC Educational Resources Information Center

    Leslie, Susan

    The Family Life Education program at David Thompson Secondary School is a one semester course dealing with human sexuality. Given to eleventh grade students the course is directed at helping students understand the emotional and social dimensions of their sexuality. Because the emphasis in the course was on feeling, not fact, this evaluation of…

  20. Inconvenient Truths: A Response to the Article by David Stoesz, "The Child Welfare Cartel"

    ERIC Educational Resources Information Center

    Clark, James J.; Yegidis, Bonnie L.

    2016-01-01

    David Stoesz offers a sweeping critique of the Children's Bureau and social work education by claiming the existence of a "child welfare cartel." He also attacks the quality of social work education and research, which he claims has poorly invested government funding and helped create the unmitigated failures of the American child…

  1. World's Youth Connect through Global Nomads Group: An Interview with GNG's David Macquart

    ERIC Educational Resources Information Center

    Morrison, James L.; Macquart, David

    2006-01-01

    Editor-in-chief James L. Morrison talks with David Macquart, co-founder of the Global Nomads Group (GNG), a group dedicated to improving children's cultural understanding by bringing the world into the classroom using videoconferencing technology. GNG moderates video conferences between K-12 classes in different countries, organizes virtual…

  2. Bridging the Gap between High School and College: An Interview with David Spence

    ERIC Educational Resources Information Center

    Smith, Virginia B.

    2006-01-01

    The National Center for Public Policy and Higher Education and the Council for Adult and Experiential Learning have awarded David Spence, its 2006 Virginia B. Smith Award for Innovative Leadership in Higher Education. Mr. Spence is formerly executive vice chancellor and chief academic officer of the California State University system and now…

  3. David Kirk on Physical Education and Sport Pedagogy: In Dialogue with Steven Stolz (Part 1)

    ERIC Educational Resources Information Center

    Stolz, Steven A.; Kirk, David

    2015-01-01

    Forming the first of two articles, this dialogue begins from the dilemma posed in the writings of David Kirk that physical education is in crisis because the dominant practice of physical education as "sport-techniques" is resistant to change. In order to make sense of crisis discourse, the discussion explores the potential for change in…

  4. A Response to David Kirk: Personal/Professional Views from US Authors

    ERIC Educational Resources Information Center

    Hastie, Peter; van der Mars, Hans

    2014-01-01

    This paper represents the views of two scholars in the USA with respect to the scholar lecture presented by David Kirk at the 2012 BERA -- Physical Education and Sport Pedagogy (PESP) Special Interest Group meeting. We discuss how two unique features of the American universities have an impact on both the corporate nature of our work and our…

  5. Henry David Thoreau, Martin Luther King Jr., and the American Tradition of Protest.

    ERIC Educational Resources Information Center

    Powell, Brent

    1995-01-01

    Maintains that Henry David Thoreau and Martin Luther King, Jr. fundamentally altered the tradition of protest and reform. Compares and contrasts the role of each man in U.S. social and constitutional history. Concludes that while Thoreau lacked the broad influence of King, his writings influenced both King and Mohandas Gandhi. (CFR)

  6. The Fifties ... Fifty Years Later: "Connection" Interviews Historian David Halberstam on a Half Century of Change

    ERIC Educational Resources Information Center

    Connection: The Journal of the New England Board of Higher Education, 2005

    2005-01-01

    This article presents an interview with historian David Halberstam who graduated from Harvard University in 1955 after serving as managing editor of the "Harvard Crimson." Upon graduation, he joined the staff of the "Daily Times Leader" newspaper of West Point, Mississippi, and then moved on to the "Nashville Tennessean," where he covered the…

  7. Simulating the Camp David Negotiations: A Problem-Solving Tool in Critical Pedagogy

    ERIC Educational Resources Information Center

    McMahon, Sean F.; Miller, Chris

    2013-01-01

    This article reflects critically on simulations. Building on the authors' experience simulating the Palestinian-Israeli-American Camp David negotiations of 2000, they argue that simulations are useful pedagogical tools that encourage creative--but not critical--thinking and constructivist learning. However, they can also have the deleterious…

  8. Investing in the Child Welfare Workforce: A Response to David Stoesz

    ERIC Educational Resources Information Center

    Briar-Lawson, Katharine; Leake, Robin; Dickinson, Nancy; McCarthy, Mary; Anderson, Gary; Groza, Victor; Gilmore, Grover C.

    2016-01-01

    Responding to David Stoesz's invited article criticizing the Children's Bureau and the National Child Welfare Workforce Institute (NCWWI), the author's inaccurate assertions are challenged, and new information is provided about the significant work underway to support the child welfare workforce. The Children's Bureau has made historic investments…

  9. Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

    PubMed

    Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

    2008-03-14

    CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

  10. Association between shortage of energy supply and nuclear gene mutations leading to carcinomatous transformation

    PubMed Central

    DU, JIANPING

    2016-01-01

    Anaerobic bacteria use glycolysis, an oxygen-independent metabolic pathway, whereas energy metabolism in the evolved eukaryotic cell is performed via oxidative phosphorylation, with all eukaryotic cell activities depending upon high energy consumption. However, in cancer cells evolving from eukaryotic cells, the energy metabolism switches from oxidative phosphorylation to glycolysis. The shortage of energy supply induces cancer cells to acquire specific characteristics. Base pair renewal is the most energy-consuming process in the cell, and shortage of energy supply may lead to errors in this process; the more prominent the shortage in energy supply, the more errors are likely to occur in base pair renewal, resulting in gene mutations and expression of cancer cell characteristics. Thus, shortage of energy supply is associated with carcinomatous transformation. PMID:26835010

  11. Numerical simulations of cloud rise phenomena associated with nuclear bursts: compressible and low Mach approaches

    NASA Astrophysics Data System (ADS)

    Kanarska, Y.; Lomov, I.; Antoun, T.

    2008-12-01

    The nuclear cloud rise is a two stage phenomenon. The initial phase (fireball expansion) of the cloud formation is dominated by compressible flow effects and propagation of shock waves. At the later stage, shock waves become weak, the Mach number decreases and the time steps required by an explicit code to model the acoustic waves make simulation of the late time cloud dynamics with a compressible code very expensive. The buoyant cloud rise at this stage can be efficiently simulated by low Mach-number approximation. In this approach acoustic waves are removed analytically, compressible effects are included as a non-zero divergence constraint due to background stratification and the system of equations is solved implicitly using pressure projection methods. Our numerical approach includes fluid mechanical models that are able to simulate both compressible, incompressible and low Mach regimes. Compressible dynamics is simulated with the explicit high order Eulerian code GEODYN (Lomov et al., 2001). It is based on the second-order Godunov method of Colella and Woodward (1984) that is extended for multiple dimensions using operator-splitting. The code includes the material interface tracking based on a volume-of-fluid (VOF) approach of Miller and Puckett (1996). The code we use for the low Mach approximation (LMC) is based on the incompressible solver of Bell et al., (2003). An unsplit second-order Godunov method and the MAC projection method (Bell et al., 2003) are used. An algebraic slip multiphase model is implemented to describe fallout of dust particles. Both codes incorporate adaptive mesh refinement (AMR). Additionally, the codes are explicitly coupled via input/output files. First, we compared solutions for an idealized buoyant bubble rise problem, that is characterized by low Mach numbers, in GEODYN and LMC codes. While the cloud evolution process is reproduced in both codes, some differences are found in the cloud rise speed and the cloud interface structure

  12. Sinkhole-type subsidence over abandoned coal mines in St. David, Illinois. Mine subsidence report, St. David, Illinois. A field survey and analysis of mine subsidence of abandoned coal mines in St. David, Illinois

    SciTech Connect

    Wildanger, E.G.; Mahar, J.; Nieto, A.

    1980-01-01

    This study examined the geologic data, mining history, and subsidence trends of the St. David region. Mine subsidence has occurred due to collapse of the abandoned mine workings. The known subsidence areas have been mapped and described. Results of the study include: (1) St. David has been undermined by both large shipping mines and smaller local mines; (2) sinkholes will continue to develop in this area in response to rock failure and roof collapse above the abandoned mine workings; (3) some primary factors that contribute to the sinkhole problems are the undermining and roof rock composition; (4) sinkholes will be smaller in the future; (5) ten of the 63 sinkholes occurred close enough to structures to cause damage, and only six sinkholes caused damage; (6) ways to minimize potential damage to future homes from sinkhole subsidence are manageable; (7) threats to residents lie in the collapse of heavy walls, brick chimneys, breaks in gas, water, or electrical lines; and (8) location of future subsidence is not predictable. (DP)

  13. Using Molecular Initiating Events to Develop a Structural Alert Based Screening Workflow for Nuclear Receptor Ligands Associated with Hepatic Steatosis.

    PubMed

    Mellor, Claire L; Steinmetz, Fabian P; Cronin, Mark T D

    2016-02-15

    In silico models are essential for the development of integrated alternative methods to identify organ level toxicity and lead toward the replacement of animal testing. These models include (quantitative) structure-activity relationships ((Q)SARs) and, importantly, the identification of structural alerts associated with defined toxicological end points. Structural alerts are able both to predict toxicity directly and assist in the formation of categories to facilitate read-across. They are particularly important to decipher the myriad mechanisms of action that result in organ level toxicity. The aim of this study was to develop novel structural alerts for nuclear receptor (NR) ligands that are associated with inducing hepatic steatosis and to show the vast number of existing data that are available. Current knowledge on NR agonists was extended with data from the ChEMBL database (12,713 chemicals in total) of bioactive molecules and from studying NR ligand-binding interactions within the protein database (PDB, 624 human NR structure files). A computational structural alert based workflow was developed using KNIME from these data using molecular fragments and other relevant chemical features. In total, 214 structural features were recorded computationally as SMARTS strings, and therefore, they can be used for grouping and screening during drug development and hazard assessment and provide knowledge to anchor adverse outcome pathways (AOPs) via their molecular initiating events (MIEs). PMID:26787004

  14. Upregulation of neutrophil gelatinase-associated lipocalin by ErbB2 through nuclear factor-kappaB activation.

    PubMed

    Li, Shau-Hsuan; Hawthorne, Valerie S; Neal, Christopher L; Sanghera, Sartaj; Xu, Jia; Yang, Jun; Guo, Hua; Steeg, Patricia S; Yu, Dihua

    2009-12-15

    ErbB2 (HER2, neu) is a receptor tyrosine kinase overexpressed in about 25% of invasive breast carcinomas. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted glycoprotein expressed in a variety of cancers, including breast carcinomas. NGAL can inhibit erythroid cell production, leading to anemia. Anemia usually occurs in cancer patients and negatively affects quality of life. However, current treatment for cancer-related anemia has potential complications. ErbB2, NGAL, and anemia have all been associated with increased metastasis and poor prognosis in breast cancer patients, although the relationship between ErbB2 and NGAL expression is not clear. Here, using breast cancer cell lines in vitro and transgenic mice carrying the activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV-neu) in vivo, we show that ErbB2 overexpression leads to NGAL upregulation, which is dependent on nuclear factor-kappaB (NF-kappaB) activity. MMTV-neu transgenic mice developed anemia after tumor onset, and anemia progression could be partially arrested by a NF-kappaB inhibitor and ErbB2-targeted therapy. Taken together, upregulation of NGAL by ErbB2 through NF-kappaB activation is involved in cancer-related anemia, and the ErbB2, NF-kappaB, and NGAL pathways may serve as potential therapeutic targets for cancer-related anemia.

  15. Using Molecular Initiating Events to Develop a Structural Alert Based Screening Workflow for Nuclear Receptor Ligands Associated with Hepatic Steatosis.

    PubMed

    Mellor, Claire L; Steinmetz, Fabian P; Cronin, Mark T D

    2016-02-15

    In silico models are essential for the development of integrated alternative methods to identify organ level toxicity and lead toward the replacement of animal testing. These models include (quantitative) structure-activity relationships ((Q)SARs) and, importantly, the identification of structural alerts associated with defined toxicological end points. Structural alerts are able both to predict toxicity directly and assist in the formation of categories to facilitate read-across. They are particularly important to decipher the myriad mechanisms of action that result in organ level toxicity. The aim of this study was to develop novel structural alerts for nuclear receptor (NR) ligands that are associated with inducing hepatic steatosis and to show the vast number of existing data that are available. Current knowledge on NR agonists was extended with data from the ChEMBL database (12,713 chemicals in total) of bioactive molecules and from studying NR ligand-binding interactions within the protein database (PDB, 624 human NR structure files). A computational structural alert based workflow was developed using KNIME from these data using molecular fragments and other relevant chemical features. In total, 214 structural features were recorded computationally as SMARTS strings, and therefore, they can be used for grouping and screening during drug development and hazard assessment and provide knowledge to anchor adverse outcome pathways (AOPs) via their molecular initiating events (MIEs).

  16. Apoptosis induced by the nuclear death domain protein p84N5 is inhibited by association with Rb protein.

    PubMed

    Doostzadeh-Cizeron, J; Evans, R; Yin, S; Goodrich, D W

    1999-10-01

    Rb protein inhibits both cell cycle progression and apoptosis. Interaction of specific cellular proteins, including E2F1, with Rb C-terminal domains mediates cell cycle regulation. In contrast, the nuclear N5 protein associates with an Rb N-terminal domain with unknown function. The N5 protein contains a region of sequence similarity to the death domain of proteins involved in apoptotic signaling. We demonstrate here that forced N5 expression potently induces apoptosis in several tumor cell lines. Mutation of conserved residues within the death domain homology compromise N5-induced apoptosis, suggesting that it is required for normal function. Endogenous N5 protein is specifically altered in apoptotic cells treated with ionizing radiation. Furthermore, dominant interfering death domain mutants compromise cellular responses to ionizing radiation. Finally, physical association with Rb protein inhibits N5-induced apoptosis. We propose that N5 protein plays a role in the regulation of apoptosis and that Rb directly coordinates cell proliferation and apoptosis by binding specific proteins involved in each process through distinct protein binding domains. PMID:10512864

  17. Thermal impact of waste emplacement and surface cooling associated with geologic disposal of nuclear waste

    SciTech Connect

    Wang, J.S.Y.; Mangold, D.C.; Spencer, R.K.; Tsang, C.F.

    1982-08-01

    The thermal effects associated with the emplacement of aged radioactive wastes in a geologic repository were studied, with emphasis on the following subjects: the waste characteristics, repository structure, and rock properties controlling the thermally induced effects; the current knowledge of the thermal, thermomechanical, and thermohydrologic impacts, determined mainly on the basis of previous studies that assume 10-year-old wastes; the thermal criteria used to determine the repository waste loading densities; and the technical advantages and disadvantages of surface cooling of the wastes prior to disposal as a means of mitigating the thermal impacts. The waste loading densities determined by repository designs for 10-year-old wastes are extended to older wastes using the near-field thermomechanical criteria based on room stability considerations. Also discussed are the effects of long surface cooling periods determined on the basis of far-field thermomechanical and thermohydrologic considerations. The extension of the surface cooling period from 10 years to longer periods can lower the near-field thermal impact but have only modest long-term effects for spent fuel. More significant long-term effects can be achieved by surface cooling of reprocessed high-level waste.

  18. Deceptive single-locus taxonomy and phylogeography: Wolbachia-associated divergence in mitochondrial DNA is not reflected in morphology and nuclear markers in a butterfly species

    PubMed Central

    Kodandaramaiah, Ullasa; Simonsen, Thomas J; Bromilow, Sean; Wahlberg, Niklas; Sperling, Felix

    2013-01-01

    The satyrine butterfly Coenonympha tullia (Nymphalidae: Satyrinae) displays a deep split between two mitochondrial clades, one restricted to northern Alberta, Canada, and the other found throughout Alberta and across North America. We confirm this deep divide and test hypotheses explaining its phylogeographic structure. Neither genitalia morphology nor nuclear gene sequence supports cryptic species as an explanation, instead indicating differences between nuclear and mitochondrial genome histories. Sex-biased dispersal is unlikely to cause such mito-nuclear differences; however, selective sweeps by reproductive parasites could have led to this conflict. About half of the tested samples were infected by Wolbachia bacteria. Using multilocus strain typing for three Wolbachia genes, we show that the divergent mitochondrial clades are associated with two different Wolbachia strains, supporting the hypothesis that the mito-nuclear differences resulted from selection on the mitochondrial genome due to selective sweeps by Wolbachia strains. PMID:24455146

  19. Nuclear sequestration of COL1A1 mRNA transcript associated with type I osteogenesis imperfecta (OI)

    SciTech Connect

    Primorac, D.; Stover, M.L.; McKinstry, M.B.

    1994-09-01

    Previously we identified an OI type I patient with a splice donor mutation that resulted in intron 26 retention instead of exon skipping and sequestration of normal levels of the mutant transcript in the nuclear compartment. Intron retention was consistent with the exon definition hypothesis for splice site selection since the size of the exon-intron-exon unit was less than 300 bp. Furthermore, the retained intron contained in-frame stop codons which is thought to cause the mutant RNA to remain within the nucleus rather than appearing in the cytoplasm. To test these hypotheses, genomic fragments containing the normal sequence or the donor mutation were cloned into a collagen minigene and expressed in stably tansfected NIH 3T3 cells. None of the modifications to the normal intron altered the level of RNA that accumulated in the cytoplasm, as expected. However none of the modifications to the mutant intron allowed accumulation of normal levels of mRNA in the cytoplasm. Moreover, in contrast to our findings in the patient`s cells only low levels of mutant transcript were found in the nucleus; a fraction of the transcript did appear in the cytoplasm which had spliced the mutant donor site correctly. Nuclear run-on experiments demonstrated equal levels of transcription from each transgene. Expression of another donor mutation known to cause in-frame exon skipping in OI type IV was accurately reproduced in the minigene in transfected 3T3 cells. Our experience suggests that either mechanism can lead to formation of a null allele possibly related to the type of splicing events surrounding the potential stop codons. Understanding the rules governing inactivation of a collagen RNA transcript may be important in designing a strategy to inactivate a dominate negative mutation associated with the more severe forms of OI.

  20. Fluxes of radiocaesium associated with suspended sediment in rivers impacted by the Fukushima Daiichi Nuclear Power Plant

    NASA Astrophysics Data System (ADS)

    Smith, Hugh; Blake, Will; Onda, Yuichi; Yoshimura, Kazuya; Taniguchi, Keisuke; Yamashiki, Yosuke; Matsuura, Yuki; Taylor, Alex

    2014-05-01

    The Fukushima Daiichi Nuclear Power Plant accident which followed the earthquake and tsunami on 11 March 2011 resulted in the release of Cs-134 and Cs-137 into the surrounding environment, where highly elevated levels are reported. There is considerable concern about the redistribution of these radioactive contaminants from the atmosphere to vegetation, soil and aquatic systems. Fluvial redistribution of radiocaesium may contaminate downstream areas that were subject to low fallout and deliver significant quantities of highly contaminated fine sediment to the coastal zone. This study reports on the magnitude of fluvial transfer of Cs-134 and Cs-137 through river networks located across the fallout region. Initially six nested river monitoring stations were established within the Abukuma River basin from June 2011. Subsequently, an additional 23 stations were established between October 2012 and January 2013, which included stations within the Abukuma basin as well as smaller coastal catchments north and south of the power plant. Combined, these 29 sites represent a globally-unique river monitoring network designed to quantify sediment-associated transfer of radiocaesium from headwaters to the Pacific Coast of Japan. The catchments range in area from 8 to 5,172 km2 and span a large range in spatially-averaged radiocaesium inventories. Flow and turbidity (converted to suspended sediment concentration) were measured at each station while bulk suspended sediment samples were collected at regular intervals using time-integrated samplers to allow measurement of Cs-134 and Cs-137 activity concentrations by gamma spectrometry. Preliminary monitoring data showed highly elevated but also highly variable fluxes of radiocaesium in rivers across the fallout region. High magnitude flows in response to typhoon events exported large quantities of radiocaesium. Rivers are an important and continuing source of radiocaesium input to the coastal environment and the Pacific Ocean in

  1. Variants in Hepatocyte Nuclear Factor 4α Are Modestly Associated With Type 2 Diabetes in Pima Indians

    PubMed Central

    Muller, Yunhua Li; Infante, Aniello M.; Hanson, Robert L.; Love-Gregory, Latisha; Knowler, William; Bogardus, Clifton; Baier, Leslie J.

    2005-01-01

    Single nucleotide polymorphisms (SNPs) within the hepatocyte nuclear factor 4α (HNF4α) gene are associated with type 2 diabetes in Finns and Ashkenazi Jews. Previous studies in both populations have reported linkage to type 2 diabetes near the HNF4α locus on chromosome 20q12-13. To investigate whether HNF4α is a diabetes susceptibility gene in Pima Indians, a population with the highest reported prevalence of type 2 diabetes but with no evidence for linkage of the disease on chromosome 20q, 19 SNPs across the promoter and coding region of HNF4α were genotyped for association analysis. In a group of 1,037 Pima Indians (573 diabetic and 464 nondiabetic subjects), three SNPs in HNF4α (rs3212183 and rs2071197 located in introns 3 and 1, respectively, and rs6031558, an extremely rare SNP located in the P2 promoter region) were modestly associated with type 2 diabetes (rs3212183 odds ratio [OR] 1.34 [95% CI 1.07–1.67], P = 0.009; rs2071197 1.34 [1.07–1.66], P = 0.008; and rs6031558 3.18 [1.03–9.84], P = 0.04, adjusted for age, sex, birth year, heritage, and family membership). We conclude that variants in HNF4α do not appear to be major determinants for type 2 diabetes in Pima Indians; however, HNF4α may have a minor role in type 2 diabetes susceptibility within this Native American population. PMID:16186411

  2. Nuclear Multidrug Resistance-Related Protein 1 Is Highly Associated with Better Prognosis of Human Mucoepidermoid Carcinoma through the Suppression of Cell Proliferation, Migration and Invasion

    PubMed Central

    Shen, Liang-Liang; Zhao, Jin-Long; Liu, Yuan; Wu, Jun-Zheng; Liu, Yan-Pu; Yu, Bo

    2016-01-01

    Objectives Multidrug resistance-related protein 1 (MRP1) overexpression is a well acknowledged predictor of poor response to chemotherapy, but MRP1 also correlated to better prognosis in some reports, especially for patients not pretreated with chemotherapy. In our previous study, we found nuclear translocation of MRP1 in mucoepidermoid carcinoma (MEC) for the first time. The purpose of this study was to further investigate the function of nuclear MRP1 in MEC. Materials and Methods Human MEC tissue samples of 125 patients were selected and stained using immunohistochemistry. The expression level of total MRP1/nuclear MRP1 of each sample was evaluated by expression index (EI) which was scored using both qualitative and quantitative analysis. The correlations between the clinicopathologic parameters and the EI of nuclear MRP1 were analyzed using Spearman’s rank correlation analysis, respectively. The effects of RNAi-mediated downregulation of nuclear MRP1 on MEC cells were assessed using flow cytometric analysis, MTT assay, plate colony formation assay, transwell invasion assay and monolayer wound healing assay. Results In this study, we found the EI of nuclear MRP1 was negatively correlated to the pathologic grading (r = -0.498, P<0.01) / clinical staging (r = -0.41, P<0.01) / tumor stage (r = -0.28, P = 0.02) / nodal stage (r = -0.29, P<0.01) of MEC patients. The RNAi-mediated downregulation of nuclear MRP1 further proved that the downregulation of nuclear MRP1 could increase the cell replication, growth speed, colony formation efficiency, migration and invasion ability of MEC cells. Conclusion Our results suggested that nuclear MRP1 is highly associated with better prognosis of human mucoepidermoid carcinoma and further study of its function mechanism would provide clues in developing new treatment modalities of MEC. PMID:26829120

  3. Estimated association between dwelling soil contamination and internal radiation contamination levels after the 2011 Fukushima Daiichi nuclear accident in Japan

    PubMed Central

    Tsubokura, Masaharu; Nomura, Shuhei; Sakaihara, Kikugoro; Kato, Shigeaki; Leppold, Claire; Furutani, Tomoyuki; Morita, Tomohiro; Oikawa, Tomoyoshi; Kanazawa, Yukio

    2016-01-01

    Objectives Measurement of soil contamination levels has been considered a feasible method for dose estimation of internal radiation exposure following the Chernobyl disaster by means of aggregate transfer factors; however, it is still unclear whether the estimation of internal contamination based on soil contamination levels is universally valid or incident specific. Methods To address this issue, we evaluated relationships between in vivo and soil cesium-137 (Cs-137) contamination using data on internal contamination levels among Minamisoma (10–40 km north from the Fukushima Daiichi nuclear power plant), Fukushima residents 2–3 years following the disaster, and constructed three models for statistical analysis based on continuous and categorical (equal intervals and quantiles) soil contamination levels. Results A total of 7987 people with a mean age of 55.4 years underwent screening of in vivo Cs-137 whole-body counting. A statistically significant association was noted between internal and continuous Cs-137 soil contamination levels (model 1, p value <0.001), although the association was slight (relative risk (RR): 1.03 per 10 kBq/m2 increase in soil contamination). Analysis of categorical soil contamination levels showed statistical (but not clinical) significance only in relatively higher soil contamination levels (model 2: Cs-137 levels above 100 kBq/m2 compared to those <25 kBq/m2, RR=1.75, p value <0.01; model 3: levels above 63 kBq/m2 compared to those <11 kBq/m2, RR=1.45, p value <0.05). Conclusions Low levels of internal and soil contamination were not associated, and only loose/small associations were observed in areas with slightly higher levels of soil contamination in Fukushima, representing a clear difference from the strong associations found in post-disaster Chernobyl. These results indicate that soil contamination levels generally do not contribute to the internal contamination of residents in Fukushima; thus, individual

  4. Chloroplast Biogenesis-Associated Nuclear Genes: Control by Plastid Signals Evolved Prior to Their Regulation as Part of Photomorphogenesis

    PubMed Central

    Hills, Alison C.; Khan, Safina; López-Juez, Enrique

    2015-01-01

    The assembly of photosynthetically competent chloroplasts occurs in angiosperm seedlings when first exposed to light, and is due to the control by light of photosynthesis-associated nuclear genes (PhANGs), also dependent upon plastid-to-nucleus “biogenic” communication signals. The relationship between light- and plastid signal-regulation of PhANGs is close but poorly understood. In contrast, many conifers green in the dark and the promoter of a pine PhANG, Lhcb, is active in the dark in tobacco. Here, we show that the activity of this promoter in tobacco is sensitive to plastid photobleaching, or to the inhibition of plastid translation in the light or the dark, and the same interventions reduce expression of the native gene in pine seedlings, demonstrating classic plastid biogenic signaling in gymnosperms. Furthermore, Arabidopsis mutations causing defective plastid biogenesis suppress the effect in darkness of mutations in COP1 and DET1, repressors of photomorphogenesis, for the expression of several PhANGs but not a photosynthesis-unrelated, light-regulated gene. GLK transcriptional regulators mediate the response of LHCB but not of other tested PhANGs. We propose the ability to suppress PhANG response to positive plastid biogenic signals in the dark may have contributed to the evolution of light-controlled chloroplast biogenesis. PMID:26697036

  5. Phylogenomic analysis of Emiliania huxleyi provides evidence for haptophyte-stramenopile association and a chimeric haptophyte nuclear genome.

    PubMed

    Miller, John J; Delwiche, Charles F

    2015-06-01

    Emiliania huxleyi is a haptophyte alga of uncertain phylogenetic affinity containing a secondarily derived, chlorophyll c containing plastid. We sought to characterize its relationships with other taxa by quantifying the bipartitions in which it was included from a group of single protein phylogenetic trees in a way that allowed for variation in taxonomic content and accounted for paralogous sequences. The largest number of sequences supported a phylogenetic relationship of E. huxleyi with the stramenopiles, in particular Aureococcus anophagefferens. Far fewer nuclear sequences gave strong support to the placement of this coccolithophorid with the cryptophyte, Guillardia theta. The majority of the sequences that did support this relationship did not have plastid related functions. These results suggest that the haptophytes may be more closely allied with the heterokonts than with the cryptophytes. Another small set of genes associated E. huxleyi with the Viridiplantae with high support. While these genes could have been acquired with a plastid, the lack of plastid related functions among the proteins for which they code and the lack of other organisms with chlorophyll c containing plastids within these bipartitions suggests other explanations may be possible. This study also identified several genes that may have been transferred from the haptophyte lineage to the dinoflagellates Karenia brevis and Karlodinium veneficum as a result of their haptophyte derived plastid, including some with non-photosynthetic functions.

  6. Factors associated with nurses' intention to leave their jobs after the Fukushima Daiichi Nuclear Power plant accident.

    PubMed

    Sato, Yoshinobu; Hayashida, Naomi; Orita, Makiko; Urata, Hideko; Shinkawa, Tetsuko; Fukushima, Yoshiko; Nakashima, Yumiko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

    2015-01-01

    We conducted a survey among nurses who were working at the Fukushima Medical University Hospital at the time of the Fukushima Daiichi Nuclear Power Plant accident to clarify the factors associated with their intention to leave their jobs during the radiation emergency. We asked 345 nurses (17 men and 328 women) about their intention to leave their jobs after the accident. We also asked about relevant factors including the participants' demographic factors, living situation, working status, and knowledge of radiation health effects. We found that living with preschoolers (OR = 1.87, 95%CI: 1.02-3.44, p = 0.042), anxiety about life in Fukushima City after the accident (OR = 5.55, 95%CI: 1.18-26.13, p = 0.030), consideration of evacuation from Fukushima after the accident (OR = 2.42, 95%CI: 1.45-4.06, p = 0.001), consideration of the possible radiation health effects in children (OR = 1.90, 95%CI: 1.02-3.44, p = 0.042), and anxiety about relationships with colleagues in the hospital after the accident (OR = 3.23, p = 0.001) were independently associated with the nurses' intention to leave their jobs after the accident. On the other hand, the percentage of nurses with knowledge on radiation health effects was relatively low among those who had the intention to leave the job and among those who did not have the intention to leave the job after the accident, with no significant differences between the two groups. Our results suggest the need for an education program for nurses regarding radiation health effects.

  7. Factors Associated with Nurses’ Intention to Leave Their Jobs after the Fukushima Daiichi Nuclear Power Plant Accident

    PubMed Central

    Sato, Yoshinobu; Hayashida, Naomi; Orita, Makiko; Urata, Hideko; Shinkawa, Tetsuko; Fukushima, Yoshiko; Nakashima, Yumiko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

    2015-01-01

    We conducted a survey among nurses who were working at the Fukushima Medical University Hospital at the time of the Fukushima Daiichi Nuclear Power Plant accident to clarify the factors associated with their intention to leave their jobs during the radiation emergency. We asked 345 nurses (17 men and 328 women) about their intention to leave their jobs after the accident. We also asked about relevant factors including the participants’ demographic factors, living situation, working status, and knowledge of radiation health effects. We found that living with preschoolers (OR = 1.87, 95%CI: 1.02–3.44, p = 0.042), anxiety about life in Fukushima City after the accident (OR = 5.55, 95%CI: 1.18–26.13, p = 0.030), consideration of evacuation from Fukushima after the accident (OR = 2.42, 95%CI: 1.45–4.06, p = 0.001), consideration of the possible radiation health effects in children (OR = 1.90, 95%CI: 1.02–3.44, p = 0.042), and anxiety about relationships with colleagues in the hospital after the accident (OR = 3.23, p = 0.001) were independently associated with the nurses’ intention to leave their jobs after the accident. On the other hand, the percentage of nurses with knowledge on radiation health effects was relatively low among those who had the intention to leave the job and among those who did not have the intention to leave the job after the accident, with no significant differences between the two groups. Our results suggest the need for an education program for nurses regarding radiation health effects. PMID:25816345

  8. Factors associated with nurses' intention to leave their jobs after the Fukushima Daiichi Nuclear Power plant accident.

    PubMed

    Sato, Yoshinobu; Hayashida, Naomi; Orita, Makiko; Urata, Hideko; Shinkawa, Tetsuko; Fukushima, Yoshiko; Nakashima, Yumiko; Kudo, Takashi; Yamashita, Shunichi; Takamura, Noboru

    2015-01-01

    We conducted a survey among nurses who were working at the Fukushima Medical University Hospital at the time of the Fukushima Daiichi Nuclear Power Plant accident to clarify the factors associated with their intention to leave their jobs during the radiation emergency. We asked 345 nurses (17 men and 328 women) about their intention to leave their jobs after the accident. We also asked about relevant factors including the participants' demographic factors, living situation, working status, and knowledge of radiation health effects. We found that living with preschoolers (OR = 1.87, 95%CI: 1.02-3.44, p = 0.042), anxiety about life in Fukushima City after the accident (OR = 5.55, 95%CI: 1.18-26.13, p = 0.030), consideration of evacuation from Fukushima after the accident (OR = 2.42, 95%CI: 1.45-4.06, p = 0.001), consideration of the possible radiation health effects in children (OR = 1.90, 95%CI: 1.02-3.44, p = 0.042), and anxiety about relationships with colleagues in the hospital after the accident (OR = 3.23, p = 0.001) were independently associated with the nurses' intention to leave their jobs after the accident. On the other hand, the percentage of nurses with knowledge on radiation health effects was relatively low among those who had the intention to leave the job and among those who did not have the intention to leave the job after the accident, with no significant differences between the two groups. Our results suggest the need for an education program for nurses regarding radiation health effects. PMID:25816345

  9. Aberrant gene expression patterns in placentomes are associated with phenotypically normal and abnormal cattle cloned by somatic cell nuclear transfer.

    PubMed

    Everts, Robin E; Chavatte-Palmer, Pascale; Razzak, Anthony; Hue, Isabelle; Green, Cheryl A; Oliveira, Rosane; Vignon, Xavier; Rodriguez-Zas, Sandra L; Tian, X Cindy; Yang, Xiangzhong; Renard, Jean-Paul; Lewin, Harris A

    2008-03-14

    Transcription profiling of placentomes derived from somatic cell nuclear transfer (SCNT, n = 20), in vitro fertilization (IVF, n = 9), and artificial insemination (AI, n = 9) at or near term development was performed to better understand why SCNT and IVF often result in placental defects, hydrops, and large offspring syndrome (LOS). Multivariate analysis of variance was used to distinguish the effects of SCNT, IVF, and AI on gene expression, taking into account the effects of parturition (term or preterm), sex of fetus, breed of dam, breed of fetus, and pathological finding in the offspring (hydrops, normal, or other abnormalities). Differential expression of 20 physiologically important genes was confirmed with quantitative PCR. The largest effect on placentome gene expression was attributable to whether placentas were collected at term or preterm (i.e., whether the collection was because of disease or to obtain stage-matched controls) followed by placentome source (AI, IVF, or SCNT). Gene expression in SCNT placentomes was dramatically different from AI (n = 336 genes; 276 >2-fold) and from IVF (n = 733 genes; 162 >2-fold) placentomes. Functional analysis of differentially expressed genes (DEG) showed that IVF has significant effects on genes associated with cellular metabolism. In contrast, DEG associated with SCNT are involved in multiple pathways, including cell cycle, cell death, and gene expression. Many DEG were shared between the gene lists for IVF and SCNT comparisons, suggesting that common pathways are affected by the embryo culture methods used for IVF and SCNT. However, the many unique gene functions and pathways affected by SCNT suggest that cloned fetuses may be starved and accumulating toxic wastes due to placental insufficiency caused by reprogramming errors. Many of these genes are candidates for hydrops and LOS.

  10. David crighton, 1942-2000: a commentary on his career and his influence on aeroacoustic theory

    NASA Astrophysics Data System (ADS)

    Ffowcs Williams, John E.

    David Crighton, a greatly admired figure in fluid mechanics, Head of the Department of Applied Mathematics and Theoretical Physics at Cambridge, and Master of Jesus College, Cambridge, died at the peak of his career. He had made important contributions to the theory of waves generated by unsteady flow. Crighton's work was always characterized by the application of rigorous mathematical approximations to fluid mechanical idealizations of practically relevant problems. At the time of his death, he was certainly the most influential British applied mathematical figure, and his former collaborators and students form a strong school that continues his special style of mathematical application. Rigorous analysis of well-posed aeroacoustical problems was transformed by David Crighton.

  11. David Barker, Buruli ulcer and the epidemiology of a neglected tropical disease.

    PubMed

    Phillips, D I W

    2015-10-01

    In 1969, David Barker, his wife and four children moved to Uganda to work at Makerere Medical School in the capital Kampala. During the 1960s, Makerere had become a research and teaching centre with an international reputation based on the work of Trowell, Burkitt, Hutt and many others who had pioneered studies explaining the disease patterns in the West Nile area on the basis of the local climate, nutrition and lifestyle. David Barker was funded by the Medical Research Council to carry out research on a poorly understood disease, Buruli ulcer, joining Scottish surgeon Wilson Carswell, who was later to achieve fame as the role model for Dr Garrigan in Giles Foden's novel The Last King of Scotland.

  12. Forkhead Box M1 Is Essential for Nuclear Localization of Glioma-associated Oncogene Homolog 1 in Glioblastoma Multiforme Cells by Promoting Importin-7 Expression*

    PubMed Central

    Xue, Jianfei; Zhou, Aidong; Tan, Christina; Wu, Yamei; Lee, Hsueh-Te; Li, Wenliang; Xie, Keping; Huang, Suyun

    2015-01-01

    The transcription factors glioma-associated oncogene homolog 1 (GLI1), a primary marker of Hedgehog pathway activation, and Forkhead box M1 (FOXM1) are aberrantly activated in a wide range of malignancies, including glioma. However, the mechanism of nuclear localization of GLI1 and whether FOXM1 regulates the Hedgehog signaling pathway are poorly understood. Here we found that FOXM1 promotes nuclear import of GLI1 in glioblastoma multiforme cells and thus increases the expression of its target genes. Conversely, knockdown of FOXM1 expression with FOXM1 siRNA abrogated its nuclear import and inhibited the expression of its target genes. Also, genetic deletion of FOXM1 in mouse embryonic fibroblasts abolished nuclear localization of GLI1. We observed that FOXM1 directly binds to the importin-7 (IPO7) promoter and increases its promoter activity. IPO7 interacted with GLI1, leading to enhanced nuclear import of GLI1. Depletion of IPO7 by IPO7 siRNA reduced nuclear accumulation of GLI1. In addition, FOXM1 induced nuclear import of GLI1 by promoting IPO7 expression. Moreover, the FOXM1/IPO7/GLI1 axis promoted cell proliferation, migration, and invasion in vitro. Finally, expression of FOXM1 was markedly correlated with that of GLI1 in human glioblastoma specimens. These data suggest that FOXM1 and GLI1 form a positive feedback loop that contributes to glioblastoma development. Furthermore, our study revealed a mechanism that controls nuclear import of GLI1 in glioblastoma multiforme cells. PMID:26085085

  13. Nup84, A Novel Nucleoporin That Is Associated With CAN/Nup214 on the Cytoplasmic Face of the Nuclear Pore Complex

    PubMed Central

    Bastos, Ricardo; Pouplana, Lluis Ribas de; Enarson, Mark; Bodoor, Khaldon; Burke, Brian

    1997-01-01

    The short filaments extending from the cytoplasmic face of nuclear pore complexes are thought to contain docking sites for nuclear import substrates. One component of these filaments is the large O-linked glycoprotein CAN/Nup214. Immunoprecipitation studies carried out under nondenaturing conditions, and using a variety of antibodies, reveal a novel nonglycosylated nucleoporin, Nup84, that is tightly associated with CAN/Nup214. Consistent with such an association, Nup84 is found to be exposed on the cytoplasmic face of the nuclear pore complex. cDNA sequence analyses indicate that Nup84 contains neither the GLFG nor the XFXFG repeats that are a characteristic of a number of other nuclear pore complex proteins. Secondary structure predictions, however, suggest that Nup84 contains a coiled–coil COOH-terminal domain, a conclusion supported by the observation of significant sequence similarity between this region of the molecule and various members of the tropomyosin family. Mutagenesis and expression studies indicate that the putative coiled–coil domain is required for association with the cytoplasmic face of the nuclear pore complex, whereas it is the NH2-terminal region of Nup84 that contains the site of interaction with CAN/Nup214. These findings suggest a model in which Nup84 may function in the attachment of CAN/Nup214 to the central framework of the nuclear pore complex. In this way, Nup84 could play a central role in the organization of the interface between the pore complex and the cytoplasm. PMID:9166401

  14. NVL2, a nucleolar AAA-ATPase, is associated with the nuclear exosome and is involved in pre-rRNA processing

    SciTech Connect

    Yoshikatsu, Yuki; Ishida, Yo-ichi; Sudo, Haruka; Yuasa, Keizo; Tsuji, Akihiko; Nagahama, Masami

    2015-08-28

    Nuclear VCP-like 2 (NVL2) is a member of the chaperone-like AAA-ATPase family and is involved in the biosynthesis of 60S ribosomal subunits in mammalian cells. We previously showed the interaction of NVL2 with a DExD/H-box RNA helicase MTR4/DOB1, which is a known cofactor for an exoribonuclease complex, the exosome. This finding implicated NVL2 in RNA metabolic processes during ribosome biogenesis. In the present study, we found that a series of mutations within the ATPase domain of NVL2 causes a defect in pre-rRNA processing into mature 28S and 5.8S rRNAs. Co-immunoprecipitation analysis showed that NVL2 was associated with the nuclear exosome complex, which includes RRP6 as a nucleus-specific catalytic subunit. This interaction was prevented by depleting either MTR4 or RRP6, indicating their essential role in mediating this interaction with NVL2. Additionally, knockdown of MPP6, another cofactor for the nuclear exosome, also prevented the interaction by causing MTR4 to dissociate from the nuclear exosome. These results suggest that NVL2 is involved in pre-rRNA processing by associating with the nuclear exosome complex and that MPP6 is required for maintaining the integrity of this rRNA processing complex. - Highlights: • ATPase-deficient mutants of NVL2 have decreased pre-rRNA processing. • NVL2 associates with the nuclear exosome through interactions with MTR4 and RRP6. • MPP6 stabilizes MTR4-RRP6 interaction and allows NVL2 to interact with the complex.

  15. NEW MATERIALS DEVELOPED TO MEET REGULATORY AND TECHNICAL REQUIREMENTS ASSOCIATED WITH IN-SITU DECOMMISSIONING OF NUCLEAR REACTORS AND ASSOCIATED FACILITIES

    SciTech Connect

    Blankenship, J.; Langton, C.; Musall, J.; Griffin, W.

    2012-01-18

    For the 2010 ANS Embedded Topical Meeting on Decommissioning, Decontamination and Reutilization and Technology, Savannah River National Laboratory's Mike Serrato reported initial information on the newly developed specialty grout materials necessary to satisfy all requirements associated with in-situ decommissioning of P-Reactor and R-Reactor at the U.S. Department of Energy's Savannah River Site. Since that report, both projects have been successfully completed and extensive test data on both fresh properties and cured properties has been gathered and analyzed for a total of almost 191,150 m{sup 3} (250,000 yd{sup 3}) of new materials placed. The focus of this paper is to describe the (1) special grout mix for filling the P-Reactor vessel (RV) and (2) the new flowable structural fill materials used to fill the below grade portions of the facilities. With a wealth of data now in hand, this paper also captures the test results and reports on the performance of these new materials. Both reactors were constructed and entered service in the early 1950s, producing weapons grade materials for the nation's defense nuclear program. R-Reactor was shut down in 1964 and the P-Reactor in 1991. In-situ decommissioning (ISD) was selected for both facilities and performed as Comprehensive Environmental Response, Compensations and Liability Act actions (an early action for P-Reactor and a removal action for R-Reactor), beginning in October 2009. The U.S. Department of Energy concept for ISD is to physically stabilize and isolate intact, structurally robust facilities that are no longer needed for their original purpose of producing (reactor facilities), processing (isotope separation facilities), or storing radioactive materials. Funding for accelerated decommissioning was provided under the American Recovery and Reinvestment Act. Decommissioning of both facilities was completed in September 2011. ISD objectives for these CERCLA actions included: (1) Prevent industrial worker

  16. Astronaut David Wolf participates in training for contingency EVA in WETF

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Astronaut David A. Wolf participates in training for contingency extravehicular activity (EVA) for the STS-58 mission. The mission specialist was about to be submerged ito a point of neutral buoyancy in the JSC Weightless Environment Training Facility (WETF). In this view, Wolf is displaying the flexibility of his training version of the Shuttle extravehicular mobility unit (EMU) by lifting his arms above his head (31701); Wolf waves to the camera before he is submerged in the WETF (31702).

  17. Sir David K Henderson and the origins of British occupational therapy.

    PubMed

    Pentland, Duncan; Pentland, Brian

    2015-11-01

    Sir David K Henderson made several major contributions in the field of psychiatry, gaining an international reputation but, perhaps lesser known is his role in the introduction of occupational therapy in the United Kingdom. The part Henderson played in establishing occupational therapy as an aspect of his evolving approach to treating mental illness in Scotland is discussed, as is the influence he had in stimulating and supporting the early pioneers of the profession elsewhere in the UK.

  18. Dr. David Brown poses with a portrait of Ronald McNair

    NASA Technical Reports Server (NTRS)

    1999-01-01

    In the gymnasium of Ronald McNair Magnet School in Cocoa, Fla., Dr. David Brown, a NASA astronaut, poses with a portrait of NASA astronaut Ronald McNair. The portrait was presented to the school by Walt Disney World during a tribute to McNair. The school had previously been renamed for the fallen astronaut who was one of a crew of seven who lost their lives during an accident following launch of the Space Shuttle Challenger in January 1986.

  19. Joint Seismological and Geodetic Observations on David Glacier, South Victoria Land, Antarctica

    NASA Astrophysics Data System (ADS)

    Danesi, S.; Dubbini, M.; Morelli, A.; Vittuari, L.; Bannister, S.

    2006-12-01

    Ice streams play a major role in the ice mass balance and in the reckoning of the global sea level; they have therefore been the object of wide scientific interest in the last three decades. During the 21st Italian Antarctic Expedition, in the austral summer 2005-06, we deployed a joint seismographic and geodetic network in the area of the David Glacier, Southern Victoria Land. This followed a similar experiment carried out in the same area during the austral summer 2003-04 (19th Expedition) which involved the deployment of a seismographic network which recorded significant microseismicity beneath the David Glacier, primarily occurring as a few small clusters. In the latest 2006-06 deployment 7 seismographic stations and 3 GPS geodetic receivers operated continuously for a period of 3 months (November 2006-early February 2006) in an area of about 100x50 square km around the David Glacier. The seismic stations were sited on rocky outcrops around the ice flow, and were all equipped with a broad-band seismometer and a digitizer. Contemporaneous geodetic GPS measurements were made on two points located on the glacial body: the first site close to the 2003-04 epicentres and to the David Glacier ice fall, the second site on the floating Drygalski Ice Tongue. A primary master GPS receiver for the kinematic processing was installed on a benchmark located on the Hughes Bluff rock outcrop. Several analyses are planned utilising the combined data sets. These include examining the temporal evolution in earthquake magnitude and locations and also the contemporaneous observation of both seismic activity and surface kinematics of the ice stream to possibly correlate the registered microseismicity with potential surges of the glacier, eventually affected by the Ross Sea tides. Here we present some details of the two temporary networks and preliminary results and implications.

  20. Rittenhouse, David (1732-96) and Rittenhouse, Benjamin (1740-1825)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    David was an instrument-maker and astronomer, born in Paper Mill Run, PA, self-taught, as a young man he made clocks and telescopes, introduced the use of spider's webs as cross-hairs in transit telescopes and made orreries to show planetary motions. He used his own instruments for astronomy. He worked to survey the MASON and DIXON line and taught astronomy at the University of Pennsylvania. He b...

  1. An interview with Dr Kenneth Kornman. Interview by David W Richards.

    PubMed

    Kornman, Kenneth

    2011-10-01

    Inflammation is recognized as the major underlying contributor to a number of chronic diseases, amongst them periodontitis and cardiovascular diseases. The relationship between these diseases is explored and commented on in this question-and-answer session between Ken Kornman, D.D.S., Ph.D., the editor of the Journal of Periodontology and David Richards, D.D.S., Ph.D., a former student of Dr. Kornman's. Practical suggestions and guidelines for the dentist are also examined.

  2. Spicy science: David Julius and the discovery of temperature-sensitive TRP channels

    PubMed Central

    Bautista, Diana M

    2015-01-01

    This invited biographical review covers the career of Dr. David Julius and his discovery of thermosensitive TRP channels. Dr. Julius is currently the Morris Herzstein Chair in Molecular Biology and Medicine and Professor and Chair of Physiology at the University of California, San Francisco Medical School. He is a member of the National Academy of Sciences and has received many distinguished awards for his landmark discoveries of the molecular basis of pain and thermosensation. PMID:27227012

  3. Astronauts David Scott looks at sample referred to as 'genesis rock'

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronauts David R. Scott, right, commander of the Apollo 15 mission, gets a close look at the sample referred to as the 'genesis rock' in the Non-Sterile Nitrogen Processing Line (NNPL) in the Lunar Receiving Laboratory (LRL) at the Manned Spacecraft Center (MSC). Scientist-Astronaut Joseph P. Allen, left, an Apollo 15 spacecraft communicator, looks on. The white-colored rock has been given the permanent identification number of 15415.

  4. The translation initiation factor 3 subunit eIF3K interacts with PML and associates with PML nuclear bodies

    SciTech Connect

    Salsman, Jayme; Pinder, Jordan; Tse, Brenda; Corkery, Dale; Dellaire, Graham

    2013-10-15

    The promyelocytic leukemia protein (PML) is a tumor suppressor protein that regulates a variety of important cellular processes, including gene expression, DNA repair and cell fate decisions. Integral to its function is the ability of PML to form nuclear bodies (NBs) that serve as hubs for the interaction and modification of over 90 cellular proteins. There are seven canonical isoforms of PML, which encode diverse C-termini generated by alternative pre-mRNA splicing. Recruitment of specific cellular proteins to PML NBs is mediated by protein–protein interactions with individual PML isoforms. Using a yeast two-hybrid screen employing peptide sequences unique to PML isoform I (PML-I), we identified an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in the process identified a novel eIF3K isoform, which we term eIF3K-2. We further demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as well as in vivo within human cells by co-immunoprecipitation and co-immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3 translation pre-initiation complex to interact directly with the PML protein, and provide data implicating alternative splicing of both PML and eIF3K as a possible regulatory mechanism for eIF3K localization at PML NBs. - Highlights: • The PML-I C-terminus, encoded by exon 9, interacts with translation factor eIF3K. • We identify a novel eIF3K isoform that excludes exon 2 (eIF3K-2). • eIF3K-2 preferentially associates with PML bodies enriched in PML-I vs. PML-IV. • Alternative splicing of eIF3K regulates association with PML bodies.

  5. Tissue specificity of the hormonal response in sex accessory tissues is associated with nuclear matrix protein patterns.

    PubMed

    Getzenberg, R H; Coffey, D S

    1990-09-01

    The DNA of interphase nuclei have very specific three-dimensional organizations that are different in different cell types, and it is possible that this varying DNA organization is responsible for the tissue specificity of gene expression. The nuclear matrix organizes the three-dimensional structure of the DNA and is believed to be involved in the control of gene expression. This study compares the nuclear structural proteins between two sex accessory tissues in the same animal responding to the same androgen stimulation by the differential expression of major tissue-specific secretory proteins. We demonstrate here that the nuclear matrix is tissue specific in the rat ventral prostate and seminal vesicle, and undergoes characteristic alterations in its protein composition upon androgen withdrawal. Three types of nuclear matrix proteins were observed: 1) nuclear matrix proteins that are different and tissue specific in the rat ventral prostate and seminal vesicle, 2) a set of nuclear matrix proteins that either appear or disappear upon androgen withdrawal, and 3) a set of proteins that are common to both the ventral prostate and seminal vesicle and do not change with the hormonal state of the animal. Since the nuclear matrix is known to bind androgen receptors in a tissue- and steroid-specific manner, we propose that the tissue specificity of the nuclear matrix arranges the DNA in a unique conformation, which may be involved in the specific interaction of transcription factors with DNA sequences, resulting in tissue-specific patterns of secretory protein expression.

  6. University Mentality or Community College Paranoia: A Critique of Don Morgan's Reaction to David Riesman's Tentative Hypotheses.

    ERIC Educational Resources Information Center

    Vaughan, George B.

    1979-01-01

    Responds to Don Morgan's reaction (JC 502 050) to David Riesman's article, "Community Colleges: Some Tentative Hypotheses" (JC 502 056). Summarizes Riesman's major arguments and challenges Morgan's interpretations of them. (AYC)

  7. Investigating the degree of "stigma" associated with nuclear energy technologies: A cross-cultural examination of the case of fusion power.

    PubMed

    Horlick-Jones, Tom; Prades, Ana; Espluga, Josep

    2012-07-01

    The extent to which nuclear energy technologies are, in some sense, "stigmatised" by historical environmental and military associations is of particular interest in contemporary debates about sustainable energy policy. Recent claims in the literature suggest that despite such stigmatisation, lay views on such technologies may be shifting towards a "reluctant acceptance," in the light of concerns about issues like anthropogenic climate change. In this paper, we report on research into learning and reasoning processes concerned with a largely unknown nuclear energy technology; namely fusion power. We focus on the role of the nuclear label, or "brand," in informing how lay citizens make sense of the nature of this technology. Our findings derive from a comparative analysis of data generated in Spain and Britain, using the same methodology.

  8. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis.

    PubMed

    Bucerius, Jan; Hyafil, Fabien; Verberne, Hein J; Slart, Riemer H J A; Lindner, Oliver; Sciagra, Roberto; Agostini, Denis; Übleis, Christopher; Gimelli, Alessia; Hacker, Marcus

    2016-04-01

    Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on

  9. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM) on PET imaging of atherosclerosis.

    PubMed

    Bucerius, Jan; Hyafil, Fabien; Verberne, Hein J; Slart, Riemer H J A; Lindner, Oliver; Sciagra, Roberto; Agostini, Denis; Übleis, Christopher; Gimelli, Alessia; Hacker, Marcus

    2016-04-01

    Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on

  10. ER-associated SNAREs and Sey1p mediate nuclear fusion at two distinct steps during yeast mating.

    PubMed

    Rogers, Jason V; Arlow, Tim; Inkellis, Elizabeth R; Koo, Timothy S; Rose, Mark D

    2013-12-01

    During yeast mating, two haploid nuclei fuse membranes to form a single diploid nucleus. However, the known proteins required for nuclear fusion are unlikely to function as direct fusogens (i.e., they are unlikely to directly catalyze lipid bilayer fusion) based on their predicted structure and localization. Therefore we screened known fusogens from vesicle trafficking (soluble N-ethylmaleimide-sensitive factor attachment protein receptors [SNAREs]) and homotypic endoplasmic reticulum (ER) fusion (Sey1p) for additional roles in nuclear fusion. Here we demonstrate that the ER-localized SNAREs Sec20p, Ufe1p, Use1p, and Bos1p are required for efficient nuclear fusion. In contrast, Sey1p is required indirectly for nuclear fusion; sey1Δ zygotes accumulate ER at the zone of cell fusion, causing a block in nuclear congression. However, double mutants of Sey1p and Sec20p, Ufe1p, or Use1p, but not Bos1p, display extreme ER morphology defects, worse than either single mutant, suggesting that retrograde SNAREs fuse ER in the absence of Sey1p. Together these data demonstrate that SNAREs mediate nuclear fusion, ER fusion after cell fusion is necessary to complete nuclear congression, and there exists a SNARE-mediated, Sey1p-independent ER fusion pathway.

  11. Toxinotyping of Clostridium perfringens fecal isolates of reintroduced Père David's deer (Elaphurus davidianus) in China.

    PubMed

    Qiu, Huiling; Chen, Fu; Leng, Xinyan; Fei, Rongmei; Wang, Libo

    2014-10-01

    Clostridium perfringens is an important pathogen causing sudden death syndrome, necrotic enteritis, and gas gangrene in ruminants, especially some deer species. Père David's deer (Elaphurus davidianus) is one of the world's rare species and is an endangered and protected species in China. Some Père David's deer in the Chinese Shishou Père David's Deer Preserve died due to C. perfringens infection. We investigated the toxin types and C. perfringens enterotoxin-positive (cpe(+)) strains of isolated C. perfringens in Père David's deer in China. We collected 155 fecal samples from the Beijing Nanhaizi Père David's Deer Park and the Jiangsu Dafeng Père David's Deer National Nature Reserve between July 2010 and July 2011. Bacteria isolated using blood agar and mannitol agar plates were identified by Gram staining and nested PCR for 16S rRNA. We isolated C. perfringens from 41 fecal samples and used PCR amplification of five toxin genes to identify the toxinotypes and the cpe(+) strains of C. perfringens. Twenty-one isolates were type A, 15 were type E, and five were type D. Fifteen isolates were cpe(+) strains, including eight that were type A and seven that were type E.

  12. Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway.

    PubMed

    Zhu, Yaping; Shen, Jiaqi; Gao, Liyan; Feng, Youji

    2016-04-01

    Extensive exposure to estrogen is generally acknowledged as a risk factor for endometrial cancer. Given that the accumulation of adipocytes also contributes to the increased production of estrogen, in the present study, we evaluated the expression of the fat mass and obesity-associated (FTO) gene in endometrial tumor tissues and further explored the mechanism of how estrogen facilitates FTO nuclear localization and promotes endometrial cancer cell proliferation. Immunohistochemical (IHC) staining assay was used to detect the FTO expression in endometrial tumor samples. Western blotting was performed to investigate the mechanism of estrogen-induced FTO nuclear localization. siRNA was used to knock down ERα and further explore its role in FTO nuclear localization. MTT assay was carried out to determine cell proliferation. We found that FTO was overexpressed in endometrial carcinoma tissues and served as a poor prognostic marker. Additionally, estrogen induced FTO nuclear accumulation via the mTOR signaling pathway and the nuclear localization was ERα-dependent, which contributed to enhanced proliferative activity. Therefore, the present study provides new insight into the mechanisms of estrogen-induced proliferation, implying the possibility of using FTO as a potential therapeutic target for the treatment of endometrial cancer.

  13. Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix

    PubMed Central

    Iarovaia, Olga V.; Akopov, Sergey B.; Nikolaev, Lev G.; Sverdlov, Eugene D.; Razin, Sergey V.

    2005-01-01

    The spatial organization of an ∼170 kb region of human chromosome 19, including CD22 and GPR40–GPR43 genes, was studied using in situ hybridization of a set of cosmid and PAC probes with nuclear halos prepared from proliferating and differentiated HL60 cells. The whole region under study was found to be looped out into the nuclear halo in proliferating cells. It is likely that the loop observed was attached to the nuclear matrix via MAR elements present at the flanks of the area under study. Upon dimethyl sulfoxide-induced differentiation of the cells the looped fragment became associated with the nuclear matrix. This change in the spatial organization correlated with the activation of transcription of at least two (CD22 and GPR43) genes present within the loop. The data obtained are discussed in the framework of the hypothesis postulating that the spatial organization of chromosomal DNA is maintained via constitutive (basic) and facultative (transcription-related) interactions of the latter with the nuclear matrix. PMID:16049024

  14. Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix.

    PubMed

    Iarovaia, Olga V; Akopov, Sergey B; Nikolaev, Lev G; Sverdlov, Eugene D; Razin, Sergey V

    2005-01-01

    The spatial organization of an approximately 170 kb region of human chromosome 19, including CD22 and GPR40-GPR43 genes, was studied using in situ hybridization of a set of cosmid and PAC probes with nuclear halos prepared from proliferating and differentiated HL60 cells. The whole region under study was found to be looped out into the nuclear halo in proliferating cells. It is likely that the loop observed was attached to the nuclear matrix via MAR elements present at the flanks of the area under study. Upon dimethyl sulfoxide-induced differentiation of the cells the looped fragment became associated with the nuclear matrix. This change in the spatial organization correlated with the activation of transcription of at least two (CD22 and GPR43) genes present within the loop. The data obtained are discussed in the framework of the hypothesis postulating that the spatial organization of chromosomal DNA is maintained via constitutive (basic) and facultative (transcription-related) interactions of the latter with the nuclear matrix. PMID:16049024

  15. Modifier genes as therapeutics: the nuclear hormone receptor Rev Erb alpha (Nr1d1) rescues Nr2e3 associated retinal disease.

    PubMed

    Cruz, Nelly M; Yuan, Yang; Leehy, Barrett D; Baid, Rinku; Kompella, Uday; DeAngelis, Margaret M; Escher, Pascal; Haider, Neena B

    2014-01-01

    Nuclear hormone receptors play a major role in many important biological processes. Most nuclear hormone receptors are ubiquitously expressed and regulate processes such as metabolism, circadian function, and development. They function in these processes to maintain homeostasis through modulation of transcriptional gene networks. In this study we evaluate the effectiveness of a nuclear hormone receptor gene to modulate retinal degeneration and restore the integrity of the retina. Currently, there are no effective treatment options for retinal degenerative diseases leading to progressive and irreversible blindness. In this study we demonstrate that the nuclear hormone receptor gene Nr1d1 (Rev-Erbα) rescues Nr2e3-associated retinal degeneration in the rd7 mouse, which lacks a functional Nr2e3 gene. Mutations in human NR2E3 are associated with several retinal degenerations including enhanced S cone syndrome and retinitis pigmentosa. The rd7 mouse, lacking Nr2e3, exhibits an increase in S cones and slow, progressive retinal degeneration. A traditional genetic mapping approach previously identified candidate modifier loci. Here, we demonstrate that in vivo delivery of the candidate modifier gene, Nr1d1 rescues Nr2e3 associated retinal degeneration. We observed clinical, histological, functional, and molecular restoration of the rd7 retina. Furthermore, we demonstrate that the mechanism of rescue at the molecular and functional level is through the re-regulation of key genes within the Nr2e3-directed transcriptional network. Together, these findings reveal the potency of nuclear receptors as modulators of disease and specifically of NR1D1 as a novel therapeutic for retinal degenerations.

  16. SEPT9_i1 is required for the association between HIF-1α and importin-α to promote efficient nuclear translocation

    PubMed Central

    Golan, Maya; Mabjeesh, Nicola J

    2013-01-01

    Septin 9 isoform 1 (SEPT9_i1) protein associates with hypoxia-inducible factor (HIF)-1α to augment HIF-1 transcriptional activity. The first 25 amino acids of SEPT9_i1 (N25) are unique compared with other members of the mammalian septin family. This N25 domain is critical for HIF-1 activation by SEPT9_i1 but not essential for the protein-protein interaction. Here, we show that expression of N25 induces a significant dose-dependent inhibition of HIF-1 transcriptional activity under normoxia and hypoxia without influencing cellular HIF-1α protein levels. In vivo, N25 expression inhibits proliferation, tumor growth and angiogenesis concomitant with decreased expression levels of intratumoral HIF-1 downstream genes. Depletion of endogenous SEPT9_i1 or the exogenous expression of N25 fragment reduces nuclear HIF-1α levels accompanied by reciprocal accumulation of HIF-1α in the cytoplasm. Mechanistically, SEPT9_i1 binds to importin-α through N25 depending on its bipartite nuclear localization signal, to scaffold the association between HIF-1α and importin-α, which leads to facilitating HIF-1α nuclear translocation. Our data explore a new and a previously unrecognized role of a septin protein in the cytoplasmic-nuclear translocation process. This new level in the regulation of HIF-1α translocation is critical for efficient HIF-1 transcriptional activation that could be targeted for cancer therapeutics. PMID:24067372

  17. David's Law

    THOMAS, 113th Congress

    Rep. Jackson Lee, Sheila [D-TX-18

    2013-01-03

    01/25/2013 Referred to the Subcommittee on Crime, Terrorism, Homeland Security, And Investigations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  18. Measurement/Evaluation Techniques and Nuclear Data Associated with Fission of 239Pu by Fission Spectrum Neutrons

    SciTech Connect

    Baisden, P; Bauge, E; Ferguson, J; Gilliam, D; Granier, T; Jeanloz, R; McMillan, C; Robertson, D; Thompson, P; Verdon, C; Wilkerson, C; Young, P

    2010-03-16

    This Panel was chartered to review and assess new evaluations of work on fission product data, as well as the evaluation process used by the two U.S. nuclear weapons physics laboratories. The work focuses on fission product yields resulting from fission spectrum neutrons incident on plutonium, and includes data from measurements that had not been previously published as well as new or revised fission product cumulative yield data, and related quantities such as Q values and R values. This report documents the Panel's assessment of the work presented by Los Alamos National Laboratory (LANL) and Lawrence Livermore National Laboratory (LLNL). Based on the work presented we have seven key observations: (1) Experiments conducted in the 1970s at LANL, some of which were performed in association with a larger, NIST-led, program, have recently been documented. A preliminary assessment of this work, which will be referred to in this document as ILRR-LANL, shows it to be technically sound. (2) LLNL has done a thorough, unbiased review and evaluation of the available literature and is in the process of incorporating the previously unavailable LANL data into its evaluation of key fission product yields. The results of the LLNL effort, which includes a preliminary evaluation of the ILRR-LANL data, have been documented. (3) LANL has also conducted an evaluation of fission product yields for fission spectrum neutrons on plutonium including a meta-analysis of benchmark data as part of a planned upgrade to the ENDF/B compilation. We found that the approach of using meta-analysis provides valuable additional insight for evaluating the sparse data sets involved in this assessment. (4) Both laboratories have provided convincing evidence for energy dependence in the fission product yield of {sup 147}Nd produced from the bombardment of {sup 239}Pu with fission spectrum neutrons over an incident neutron energy range of 0.2 to 1.9 MeV. (5) Consistent, complete, and explicit treatment of

  19. OBITUARY: Eur.Ing. Professor David Dew-Hughes in memoriam

    NASA Astrophysics Data System (ADS)

    Campbell, Archie; Dew-Hughes, Denise; Donaldson, Gordon; Palmer, Richard

    2007-06-01

    We regret to announce the death of David Dew-Hughes, the second Honorary Editor of Superconductor Science and Technology, in Autumn 2006. He was born in Manchester, the eldest of three children, attended Manchester Grammar School and took his first degree in metallurgy at Birmingham, before undertaking a Doctorate of Engineering at Yale University. After initial work for IBM on semiconductors, he returned to England as a lecturer in metallurgy at Cambridge University. There he devoted his career to superconductivity long before it became fashionable, starting a group on the properties of what we now know as type II materials, with his students Jan Evetts, Archie Campbell and Anant Narlikar. Between them they paved the way to our understanding of the magnetic vortex properties of these materials, and thus to the development of modern practical materials for superconducting magnets. Eur.Ing. Professor David Dew-Hughes 1932-2006 In 1965 he became a founding Senior Lecturer in physics at Lancaster University, moving to Brookhaven National Laboratory in 1974. His final academic post was in engineering science at Oxford University where he also held a University College Tutorial Fellowship. As long ago as 1971 David wrote an authoritative review for Reports on Progress in Physics on 'The metallurgical enhancement of type II superconductors'. Following the discovery of high-Tc superconductivity, IOP Publishing launched Superconductor Science and Technology in 1988 and he was a founder member of its Editorial Board. When Jan Evetts retired as Honorary Editor in 1992, David was the natural choice as his successor. He served a five year term and remained on the Board as Deputy Editor until the end of 2000. To mark the 10th anniversary of high-temperature superconductivity in 1997, David edited a special issue of Superconductor Science and Technology in which past and present members of the Editorial Board contributed reviews of their specialities. He noted that at that time

  20. Nuclear β-catenin accumulation is associated with increased expression of Nanog protein and predicts poor prognosis of non-small cell lung cancer

    PubMed Central

    2013-01-01

    Background Although the prognostic roles of β-catenin expression in non-small cell lung cancer (NSCLC) have been reported in several immunohistochemical (IHC) studies, the results were not consistent because some studies lack sufficient number of the positive cases or did not evaluate the subcellular localization features of the protein. Method In this study, we have evaluated the expression levels and subcellular localization of β-catenin and Nanog proteins IHC staining in tissue specimens from 309 patients with NSCLC, and explored their association with clinicopathological features and patient outcome. Results We showed that patients with negative expression of membranous beta-catenin had a trend towards shorter survival (p=0.064) than those with positive expression. In contrast to previous studies, we found that increased expression of either cytoplasmic or nuclear β-catenin was strongly associated with poor prognosis and was an independent prognosticator for overall survival (p <0.01). We further found that NSCLC cells frequently exhibited an abundance of nuclear Nanog protein which was significantly correlated with nuclear β-catenin expression (p <0.01) and poor prognosis (p <0.01). Interestingly, immunofluorescent staining results revealed that increased expression of Nanog and nuclear translocation of β-catenin occurred concomitantly in response to epidermal growth factor receptor(EGFR) signaling in A549 and H23 cells. Furthermore, western blot analysis show that nuclear β-catenin rather than cytoplasmic β-catenin expression in the A549 and H23 cells can be enhanced by adding EGF, Nanog expression in the A549 and H23 cells with knockdown of β-catenin can not be obviously enhanced by adding EGF. Conclusion We propose that evaluation of subcellular localization of β-catenin and Nanog expression is of clinical significance for patients with NSCLC. PMID:23648139

  1. High nuclear grade, frequent mitotic activity, cyclin D1 and p53 overexpression are associated with stromal invasion in mammary intracystic papillary carcinoma.

    PubMed

    Zhang, Cunxian; Zhang, Peng; Hao, Jie; Quddus, M Ruhul; Steinhoff, Margaret M; Sung, C James

    2005-01-01

    Stromal invasion is identified with difficulty in routine hematoxylin-eosin-stained sections of core needle biopsy specimens from mammary intracystic papillary carcinomas. The goal of this study was to determine if nuclear grade, mitotic activity, and immunohistochemical stains for p53 and cyclin D1 would assist in differentiating intracystic papillary carcinomas without stromal invasion (ICPC) from tumors with stromal invasion (ICPC-INVA). Eight cases of ICPC and 12 cases of ICPC-INVA were reviewed. Hematoxylin-eosin slides were examined to determine the histologic features. Immunohistochemistry was performed using monoclonal antibodies to human p53 and cyclin D1. Fisher's exact test was used to compare the nuclear grade, mitotic activity, and immunoreactivity between ICPC and ICPC-INVA. High nuclear grade was more often associated with ICPC-INVA than with ICPC, although the difference was not statistically significant (p = 0.069). Frequent mitotic activity was associated with ICPC-INVA more than with ICPC (p = 0.0198). All cases of ICPC were negative for either p53 or cyclin D1, whereas 7 of 12 cases (58.3%) of ICPC-INVA were positive for either cyclin D1 alone (3 cases), p53 alone (3 cases), or both cyclin D1 and p53 (1 case) (p = 0.0147). Identical nuclear grade, mitotic activity, and immunostaining patterns were seen in the intracystic and the invasive components, and in the core biopsy and the excision of the same tumor. When any one of the positive indicators (high nuclear grade, frequent mitotic activity, or positive immunostains for cyclin D1 and/or p53) was present, the positive predictive value for stromal invasion was 91.7%. When none of the positive indicators was present, the negative predictive value was 87.5%.

  2. EDITORIAL: Van der Waals interactions in advanced materials, in memory of David C Langreth Van der Waals interactions in advanced materials, in memory of David C Langreth

    NASA Astrophysics Data System (ADS)

    Hyldgaard, Per; Rahman, Talat S.

    2012-10-01

    sufficiently close to any corrugated—and/or any smooth—surface and thus enforce a strong vdW-type adhesion; it exploits what is then essentially a contact force (dominated by the attraction exerted in the near-surface regions) to defy the pull of gravity on its own bulk. This Journal of Physics: Condensed Matter special issue is dedicated to the memory of David C Langreth. David is a dearly missed friend and mentor who inspired many of us. He was an outstanding condensed matter theorist and a scholar who greatly influenced us through his many-particle-physics based insights into density functional theory (DFT), surface science and related areas. His seminal works range from conserving formulations of interacting nonequilibrium transport [1] and formal-scattering theory [2] to an explicit formulation [3] of the exact DFT exchange-correlation energy in the adiabatic connection formula (ACF), the latter also being derived independently by Gunnarsson and Lundqvist [4]. David's portfolio also includes an analysis [5] that helped catalyze and guide the development of DFT from the local-density approximation (LDA) to the formulations of generalized gradient approximations (GGAs). Another salient contribution of David's is in the area of vdW interactions in materials. He was a key architect of the vdW density functional (vdW-DF) method [6, 7]. This method was developed in a long-standing Rutgers-Chalmers collaboration between David's group and that of Bengt I Lundqvist, later extending to a wider group of researchers on both sides of the Atlantic. Plasmons are collective excitations that depend on electron-density variation. The plasmon response can be seen as defining the nature of the LDA [4] and their description can thus also be seen as contributing to the success of GGA. The vdW-DF method is a regular constraint-based density functional (for ground-state DFT) which is derived within the ACF framework and which emphasizes the electrodynamical nature of the coupling between

  3. Cytoplasmic sequestration of FUS/TLS associated with ALS alters histone marks through loss of nuclear protein arginine methyltransferase 1.

    PubMed

    Tibshirani, Michael; Tradewell, Miranda L; Mattina, Katie R; Minotti, Sandra; Yang, Wencheng; Zhou, Hongru; Strong, Michael J; Hayward, Lawrence J; Durham, Heather D

    2015-02-01

    Mutations in the RNA-binding protein FUS/TLS (FUS) have been linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Although predominantly nuclear, this heterogenous nuclear ribonuclear protein (hnRNP) has multiple functions in RNA processing including intracellular trafficking. In ALS, mutant or wild-type (WT) FUS can form neuronal cytoplasmic inclusions. Asymmetric arginine methylation of FUS by the class 1 arginine methyltransferase, protein arginine methyltransferase 1 (PRMT1), regulates nucleocytoplasmic shuttling of FUS. In motor neurons of primary spinal cord cultures, redistribution of endogenous mouse and that of ectopically expressed WT or mutant human FUS to the cytoplasm led to nuclear depletion of PRMT1, abrogating methylation of its nuclear substrates. Specifically, hypomethylation of arginine 3 of histone 4 resulted in decreased acetylation of lysine 9/14 of histone 3 and transcriptional repression. Distribution of neuronal PRMT1 coincident with FUS also was detected in vivo in the spinal cord of FUS(R495X) transgenic mice. However, nuclear PRMT1 was not stable postmortem obviating meaningful evaluation of ALS autopsy cases. This study provides evidence for loss of PRMT1 function as a consequence of cytoplasmic accumulation of FUS in the pathogenesis of ALS, including changes in the histone code regulating gene transcription.

  4. STS-57 PLC G. David Low, in LES, listens to egress briefing at JSC's MAIL

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-57 Endeavour, Orbiter Vehicle (OV) 105, Payload Commander (PLC) and Mission Specialist (MS) G. David Low, wearing launch and entry suit (LES), smiles for the photographer during an emergency egress briefing. Low, along with the other STS-57 crewmembers, will participate in an emergency egress simulation in JSC's Crew Compartment Trainer (CCT) to familiarize himself with the procedures necessary in the event of an emergency during launch or landing aboard the space shuttle. The CCT is located in JSC's Mockup and Integration Laboratory (MAIL) Bldg 9NE.

  5. Sit Down with Sabin: David Schlegel: Hunting Dark Energy (LBNL Summer Lecture Series)

    SciTech Connect

    Russell, Sabin; Schlegel, David

    2011-06-22

    Lawrence Berkeley National Laboratory physicist and dark energy hunter David Schlegel chats with Sabin Russell, former San Francisco Chronicle reporter turned Berkeley Lab science writer, June 22, 2011. Their conversation is the first installment of "Sit Down With Sabin," a weekly conversation hosted by Russell. Over the course of five conversations with Berkeley Lab staff this summer, Russell will explore the ups and downs of innovative science — all without the aid of PowerPoint slides. Brought to you by Berkeley Lab Public Affairs.

  6. Memorial tribute to astrobiology pioneers Dr. David S. Mckay and academician Georgy A. Zavarzin

    NASA Astrophysics Data System (ADS)

    Rozanov, Alexei Y.; Rozhnov, Sergei V.; Pikuta, Elena V.; Hoover, Richard B.

    2013-09-01

    During the past two years, the world has lost two great pioneers of the field of Astrobiology-Dr. David Stewart McKay who worked at the NASA-Johnson Space Center in Houston, Texas, USA and Academician Georgy Alexandrovich Zavarzin of the Institute of Microbiology of the Russian Academy of Sciences and Professor of the Moscow State University in Moscow, Russia. The Volume of the Proceedings of the 2013 SPIE Instruments, Methods, and Missions for Astrobiology XVI is dedicated to the memory of these great scientists. We remember our dear friends and review some of their many important contributions to Planetary Science, Geology, Meteoritics, Microbiology and Astrobiology.

  7. Astronaut David Scott watching hammer and feather fall to lunar surface

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronaut David R. Scott, Apollo 15 commander, watches a geological hammer and a feather hit the lunar surface simultaneously in a test of Galileo's law of motion concerning falling bodies, as seen in this color reproduction taken from a transmission made by the RCA color television camera mounted on the Lunar Roving Vehicle. Scott released the hammer from his right hand and the feather from his left at the same instant. This experiment occured toward the end of the third and final lunar surface extravehicular activity.

  8. Johannes Kepler and David Fabricius: Their Discussion on the Nova of 1604

    NASA Astrophysics Data System (ADS)

    Granada, Miguel A.

    David Fabricius (1564-1617) was one of the most important astronomers in the period between 1596, the year of publication of Kepler's Mysterium cosmographicum, and 1609, the year of publication of the Astronomia nova.1 Kepler praised Fabricius as the most accurate observational astronomer after Tycho Brahe's death in 1601.2 Fabricius was a Reformed pastor in Ostfriesland (East Frisia), his remote natal region, and a vocational astronomer. He published nothing in the field of astronomy except for the short treatises between 1604 and 1606 concerning the nova that appeared in October 1604 in Serpentarius.

  9. Complete mitochondrial genome of the Père David's Vole, Eothenomys melanogaster (Rodentia: Arvicolinae).

    PubMed

    Chen, Shunde; Chen, Guiying; Wei, Haixue; Wang, Qiong

    2016-07-01

    The Père David's Vole, Eothenomys melanogaster belongs to subfamily Arvicolinae. It is widespread in south China, and ranges into northern Southeast Asia. In this study, the complete mitochondrial genome sequence of Eothenomys melanogaster was determined. The mitogenome is 16,331 base pairs in length. The nucleotide sequence data of 12 heavy-strand protein-coding genes of E. melanogaster and other 17 rodents were used for phylogenetic analyses. Tree constructed using Bayesian phylogenetic methods demonstrated that E. melanogaster as a sister to E. chinensis, was clustered in subfamily Arvicolinae. The monophyly of the genus Eothenomys was supported as well with Eothenomys sister to the genus Myodes.

  10. Dr. David Brown poses with students at Ronald McNair Middle School

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Dr. David Brown (right), a NASA astronaut, poses with students in the gymnasium of Ronald McNair Magnet School in Cocoa, Fla. From left, the students are Kristin Rexford, Danitra Anderson, Dominique Smith, Fallon Davis, and Qiana Taylor. Brown was at the school to attend a tribute to NASA astronaut Ronald McNair. The school had previously been renamed for the fallen astronaut who was one of a crew of seven, who lost their lives during an accident following launch of the Space Shuttle Challenger in January 1986.

  11. Best Practices Case Study: David Weekley Homes - Eagle Springs and Waterhaven, Houston, TX

    SciTech Connect

    none,

    2011-04-01

    Case study describing David Weekley Homes, Houston Division, has qualified more than 1,240 homes for the DOE Builders Challenge. Advanced framed 2x6 walls with open headers and two-stud corners allow more room for R-20 damp sprayed cellulose wall cavity insulation that is covered with R-5 rigid XPS foam. A radiant barrier cuts heat gain in the R-38 insulated vented attics. Draft stopping at fireplace and duct chases and behind tubs, gluing sheetrock to framing, and extensive caulking make for air-tight homes at 3.0 ACH50.

  12. Pallava Bagla Receives David Perlman Award for Excellence in Science Journalism-News

    NASA Astrophysics Data System (ADS)

    Stone, Richard; Bagla, Pallava

    2011-03-01

    Pallava Bagla received the David Perlman Award at the AGU Fall Meeting Honors Ceremony, held on 15 December 2010 in San Francisco, Calif. Bagla was honored for two articles. “No sign yet of Himalayan meltdown, Indian report finds,” published in Science, explores dissent among glaciologists about a prediction that Himalayan glaciers would imminently disappear. “Himalayan glaciers melting deadline ‘a mistake,’” published by BBC News, investigates the possibility that the controversial prediction resulted from a typographical error.

  13. The wonder of their voices: The 1946 Holocaust interviews of David Boder (New York: Oxford, 2010).

    PubMed

    Rosen, Alan C

    2012-05-01

    Writing a study of psychologist David Boder's 1946 displaced persons (DP) interview project gave me a chance to further document the substantial early response to the Holocaust. This was clearly one important piece of my study, and one that was eminently straightforward. Yet much of the research on Boder's project at the point in time that I carried it out was elliptical, partly because the primary interview materials were coming to light at an astonishing pace, partly because the archive collections were virtually untapped, and partly because of the misconception of Boder and his interview project itself.

  14. Complete mitochondrial genome of the Père David's Vole, Eothenomys melanogaster (Rodentia: Arvicolinae).

    PubMed

    Chen, Shunde; Chen, Guiying; Wei, Haixue; Wang, Qiong

    2016-07-01

    The Père David's Vole, Eothenomys melanogaster belongs to subfamily Arvicolinae. It is widespread in south China, and ranges into northern Southeast Asia. In this study, the complete mitochondrial genome sequence of Eothenomys melanogaster was determined. The mitogenome is 16,331 base pairs in length. The nucleotide sequence data of 12 heavy-strand protein-coding genes of E. melanogaster and other 17 rodents were used for phylogenetic analyses. Tree constructed using Bayesian phylogenetic methods demonstrated that E. melanogaster as a sister to E. chinensis, was clustered in subfamily Arvicolinae. The monophyly of the genus Eothenomys was supported as well with Eothenomys sister to the genus Myodes. PMID:26024146

  15. HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA.

    PubMed

    Ren, Xiao-Xin; Wang, Hai-Bo; Li, Chuan; Jiang, Jin-Feng; Xiong, Si-Dong; Jin, Xia; Wu, Li; Wang, Jian-Hua

    2016-02-26

    HIV-1 depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy. The cellular protein Naf1 (HIV-1 Nef-associated factor 1) is a CRM1-dependent nucleo-cytoplasmic shuttling protein, and has been identified to regulate multiple receptor-mediated signal pathways in inflammation. The cytoplasm-located Naf1 can inhibit NF-κB activation through binding to A20, and the loss of Naf1 controlled NF-κB activation is associated with multiple autoimmune diseases. However, the effect of Naf1 on HIV-1 mRNA expression has not been characterized. In this study we found that the nucleus-located Naf1 could promote nuclear export of unspliced HIV-1 gag mRNA. We demonstrated that the association between Naf1 and CRM1 was required for this function as the inhibition or knockdown of CRM1 expression significantly impaired Naf1-promoted HIV-1 production. The mutation of Naf1 nuclear export signals (NESs) that account for CRM1 recruitment for nuclear export decreased Naf1 function. Additionally, the mutation of the nuclear localization signal (NLS) of Naf1 diminished its ability to promote HIV-1 production, demonstrating that the shuttling property of Naf1 is required for this function. Our results reveal a novel role of Naf1 in enhancing HIV-1 production, and provide a potential therapeutic target for controlling HIV-1 infection.

  16. RCRA Summary Document for the David Witherspoon 1630 Site, Knoxville, Tennessee

    SciTech Connect

    Pfeffer, J.

    2008-06-10

    The 48-acre David Witherspoon, Inc. (DWI) 1630 Site operated as an unregulated industrial landfill and scrap yard. The Tennessee Division of Superfund (TDSF) closed the landfill in 1974. During the period of operation, the site received solid and liquid wastes from salvage and industrial operations. The site consists of five separate tracts of land including a small portion located across the Norfolk Southern Railroad track. The landfill occupies approximately 5 acres of the site, and roughly 20 acres of the 48 acres contains surface and buried debris associated with the DWI dismantling business operation. Beginning in 1968, the state of Tennessee licensed DWI to receive scrap metal at the DWI 1630 Site, contaminated with natural uranium and enriched uranium (235U) not exceeding 0.1 percent by weight (TDSF 1990). The U.S. Department of Energy (DOE) has agreed to undertake remedial actions at the DWI 1630 Site as specified under a Consent Order with the Tennessee Department of Environment and Conservation (TDEC) (Consent Order No. 90-3443, April 4, 1991), and as further delineated by a Memorandum of Understanding (MOU) between DOE and the State of Tennessee (MOU Regarding Implementation of Consent Orders, October 6, 1994). The soil and debris removal at the DWI 1630 Site is being performed by Bechtel Jacobs Company LLC (BJC) on behalf of the DOE. Remediation consists of removing contaminated soil and debris from the DWI 1630 site except for the landfill area and repairing the landfill cap. The DWI 1630 remediation waste that is being disposed at the Environmental Management Waste Management Facility (EMWMF) as defined as waste lot (WL) 146.1 and consists primarily of soils and soil like material, incidental debris and secondary waste generated from the excavation of debris and soil from the DWI 1630 site. The WL 146.1 includes soil, soil like material (e.g., shredded or chipped vegetation, ash), discrete debris items (e.g., equipment, drums, large scrap metal

  17. Death-domain associated protein-6 (DAXX) mediated apoptosis in hantavirus infection is counter-balanced by activation of interferon-stimulated nuclear transcription factors

    SciTech Connect

    Khaiboullina, Svetlana F.; Morzunov, Sergey P.; Boichuk, Sergei V.; Palotás, András; Jeor, Stephen St.; Lombardi, Vincent C.; Rizvanov, Albert A.

    2013-09-01

    Hantaviruses are negative strand RNA species that replicate predominantly in the cytoplasm. They also activate numerous cellular responses, but their involvement in nuclear processes is yet to be established. Using human umbilical vein endothelial cells (HUVECs), this study investigates the molecular finger-print of nuclear transcription factors during hantavirus infection. The viral-replication-dependent activation of pro-myelocytic leukemia protein (PML) was followed by subsequent localization in nuclear bodies (NBs). PML was also found in close proximity to activated Sp100 nuclear antigen and interferon-stimulated gene 20 kDa protein (ISG-20), but co-localization with death-domain associated protein-6 (DAXX) was not observed. These data demonstrate that hantavirus triggers PML activation and localization in NBs in the absence of DAXX-PLM-NB co-localization. The results suggest that viral infection interferes with DAXX-mediated apoptosis, and expression of interferon-activated Sp100 and ISG-20 proteins may indicate intracellular intrinsic antiviral attempts.

  18. The Glc7p nuclear phosphatase promotes mRNA export by facilitating association of Mex67p with mRNA.

    PubMed

    Gilbert, Wendy; Guthrie, Christine

    2004-01-30

    mRNA export is mediated by Mex67p:Mtr2p/NXF1:p15, a conserved heterodimeric export receptor that is thought to bind mRNAs through the RNA binding adaptor protein Yra1p/REF. Recently, mammalian SR (serine/arginine-rich) proteins were shown to act as alternative adaptors for NXF1-dependent mRNA export. Npl3p is an SR-like protein required for mRNA export in S. cerevisiae. Like mammalian SR proteins, Npl3p is serine-phosphorylated by a cytoplasmic kinase. Here we report that this phosphorylation of Npl3p is required for efficient mRNA export. We further show that the mRNA-associated fraction of Npl3p is unphosphorylated, implying a subsequent nuclear dephosphorylation event. We present evidence that the essential, nuclear phosphatase Glc7p promotes dephosphorylation of Npl3p in vivo and that nuclear dephosphorylation of Npl3p is required for mRNA export. Specifically, recruitment of Mex67p to mRNA is Glc7p dependent. We propose a model whereby a cycle of cytoplasmic phosphorylation and nuclear dephosphorylation of shuttling SR adaptor proteins regulates Mex67p:Mtr2p/NXF1:p15-dependent mRNA export. PMID:14759366

  19. Higher-order nuclear organization in growth arrest of human mammary epithelial cells: a novel role for telomere-associated protein TIN2

    PubMed Central

    Kaminker, Patrick; Plachot, Cedric; Kim, Sahn-Ho; Chung, Peter; Crippen, Danielle; Petersen, Ole W.; Bissell, Mina J.; Campisi, Judith; Lelièvre, Sophie A.

    2010-01-01

    Summary Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those occurring during differentiation and growth arrest. Using human mammary epithelial cells in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNase, but not RNase, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein 1γ. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in human mammary epithelial cells. Here we show that a novel extra-telomeric organization of TIN2 is associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation. PMID:15741234

  20. Higher order nuclear organization in growth arrest of humanmammary epithelial cells: A novel role for telomere-associated proteinTIN2

    SciTech Connect

    Kaminker, Patrick; Plachot, Cedric; Kim, Sahn-Ho; Chung, Peter; Crippen, Danielle; Petersen, Ole W.; Bissell, Mina J.; Campisi, Judith; Lelievre, Sophie A.

    2004-12-15

    Nuclear organization, such as the formation of specific nuclear subdomains, is generally thought to be involved in the control of cellular phenotype; however, there are relatively few specific examples of how mammalian nuclei organize during radical changes in phenotype, such as those which occur during differentiation and growth arrest. Using human mammary epithelial cells (HMECs) in which growth arrest is essential for morphological differentiation, we show that the arrest of cell proliferation is accompanied by a reorganization of the telomere-associated protein, TIN2, into one to three large nuclear subdomains. The large TIN2 domains do not contain telomeres and occur concomitant with the continued presence of TIN2 at telomeres. The TIN2 domains were sensitive to DNAse, but not RNAse, occurred frequently, but not exclusively near nucleoli, and overlapped often with dense domains containing heterochromatin protein l{gamma}. Expression of truncated forms of TIN2 simultaneously prevented the formation of TIN2 domains and relaxed the stringent morphogenesis-induced growth arrest in HMECs. Our findings reveal a novel extra-telomeric organization of TIN2 associated with the control of cell proliferation and identify TIN2 as an important regulator of mammary epithelial differentiation.

  1. Recovery of handwritten text from the diaries and papers of David Livingstone

    NASA Astrophysics Data System (ADS)

    Knox, Keith T.; Easton, Roger L., Jr.; Christens-Barry, William A.; Boydston, Kenneth

    2011-03-01

    During his explorations of Africa, David Livingstone kept a diary and wrote letters about his experiences. Near the end of his travels, he ran out of paper and ink and began recording his thoughts on leftover newspaper with ink made from local seeds. These writings suffer from fading, from interference with the printed text and from bleed through of the handwriting on the other side of the paper, making them hard to read. New image processing techniques have been developed to deal with these papers to make Livingstone's handwriting available to the scholars to read. A scan of the David Livingstone's papers was made using a twelve-wavelength, multispectral imaging system. The wavelengths ranged from the ultraviolet to the near infrared. In these wavelengths, the three different types of writing behave differently, making them distinguishable from each other. So far, three methods have been used to recover Livingstone's handwriting. These include pseudocolor (to make the different writings distinguishable), spectral band ratios (to remove text that does not change), and principal components analysis (to separate the different writings). In initial trials, these techniques have been able to lift handwriting off printed text and have suppressed handwriting that has bled through from the other side of the paper.

  2. Is success a sin? A conversation with the reverend Peter J. Gomes. Interview by David A. Light.

    PubMed

    Gomes, P J

    2001-09-01

    The difficult task of achieving worldly success while also storing up spiritual treasure is perennially with us, in good times and in bad. Today, however, as the economy has cooled and companies have demonstrated their mortality, questions about meaning and value appear more relevant, even urgent. HBR associate editor David A. Light recently spoke with the Reverend Peter J. Gomes, one of the nation's best-known preachers and the minister at Harvard University's Memorial Church, about why and how it is both possible and necessary to reconcile a life of success with a life of faith. To do so, says Gomes, you must first "get used to it"--come to terms with the age-old tension between being rich in spirit and rich in worldly goods. Second, you should "get over it"--arrive at an understanding of the value and responsibilities associated with power and wealth. Finally, "get on with it"--figure out how you can live your life spiritually while continuing to lead in the business world. For those wondering how to get on with spiritual development, Gomes cites the growing phenomenon of senior executives gathering with peers--out of shared need, not shared accomplishment--to pray, study sacred texts, and share their religious life together. He counsels that it's never too late to get on with it: We can amend life at any time, whether we're 35, 45, or 75. Gomes concludes that business will continue to be one of the most significant forces in American culture, but it will always struggle against people's need for a perspective that is beyond this world's.

  3. Increase in liver nuclear tri-iodothyronine receptors associated with increased deoxyribonucleic acid by long-term administration of tri-iodothyronine in thyroidectomized rats

    PubMed Central

    Nakamura, Hirotoshi; Hamada, Satoshi; Imura, Hiroo

    1979-01-01

    The effect of long-term administration of small amounts of tri-iodothyronine was examined on the nuclear tri-iodothyronine receptors in rat liver. The maximal binding capacity (Cmax.) and association constant (Ka) of the receptors were determined in thyroidectomized rats given vehicle alone (group A), 2μg of tri-iodothyronine/100g body wt. (group B) or 7μg of tri-iodothyronine/100g body wt. (group C) for 2 weeks. Scatchard analyses with correction for the amount of endogenous tri-iodothyronine revealed that Cmax. values per g of liver were increased to 1.5 and 2.7 times the control value in groups B and C respectively. Since concentrations of DNA per g of liver were significantly increased in the two groups of hormone-treated rats, Cmax. values per mg of DNA were nearly the same in group B, but still increased significantly in group C compared with group A. Ka values remained unchanged in all three groups of animals. Mitochondrial α-glycerophosphate dehydrogenase activity was 9.6 and 28.7 times as high in groups B and C, respectively, as in group A. Concentrations of endogenous tri-iodothyronine bound to non-histone protein were substantially increased in groups B and C, although concentrations of serum tri-iodothyronine remained rather low. The results obtained indicate that the long-term administration of tri-iodothyronine in small doses induces an increase in the nuclear receptors associated with increased DNA with and without accompanying a relative increase in the receptor concentration in thyroidectomized rats. Also the hormonal effect is closely related to the total number of the nuclear receptors and the concentrations of nuclear tri-iodothyronine bound to the receptors rather than the serum tri-iodothyronine concentrations. PMID:230825

  4. Modeling of complex wear behavior associated with grid-to-rod fretting in light water nuclear reactors

    DOE PAGESBeta

    Blau, P. J.; Qu, J.; Lu, R.

    2016-09-21

    One significant concern in the operation of light water nuclear reactors is the fretting wear damage to fuel cladding from flow-induced vibrations. For years, research on the grid-to-rod fretting (GTRF) phenomena has been underway in countries where nuclear power production is a significant industry. Under the auspices of the U.S. Department of Energy Consortium for Advanced Simulation of Light Water Reactors, an effort has been underway to develop and test an engineering wear model for zirconium alloy fuel rod cladding against a supporting grid. Furthermore, the multi-stage model accounts for oxide layers and wear rate transitions. Our paper describes themore » basis for a GTRF engineering wear model, the physical significance of the wear factor it contains, and recent progress toward model validation based on a fretting wear testing apparatus that accounts for coolant temperature, pressure, and the presence of periodic impacts (gaps) in grid/rod contact.« less

  5. Modeling of Complex Wear Behavior Associated with Grid-to-Rod Fretting in Light Water Nuclear Reactors

    NASA Astrophysics Data System (ADS)

    Blau, P. J.; Qu, J.; Lu, R.

    2016-09-01

    Fretting wear damage to fuel cladding from flow-induced vibrations can be a significant concern in the operation of light water nuclear reactors. For years, research on the grid-to-rod fretting (GTRF) phenomena has been underway in countries where nuclear power production is a significant industry. Under the auspices of the U.S. Department of Energy Consortium for Advanced Simulation of Light Water Reactors, an effort has been underway to develop and test an engineering wear model for zirconium alloy fuel rod cladding against a supporting grid. The multi-stage model accounts for oxide layers and wear rate transitions. This paper describes the basis for a GTRF engineering wear model, the physical significance of the wear factor it contains, and recent progress toward model validation based on a fretting wear testing apparatus that accounts for coolant temperature, pressure, and the presence of periodic impacts (gaps) in grid/rod contact.

  6. Behavioral differences of irradiated persons associated with the Kyshtym, Chelyabinsk, and Chernobyl Nuclear Accidents. (Reannouncement with new availability information)

    SciTech Connect

    Collins, D.L.

    1992-12-31

    Three nuclear accidents besides Chernobyl have occurred in the former Soviet Union. The accidents occurred around Kyshtym and Chelyabinsk in the Ural Mountains between 1949 and 1967 and contaminated over one-half million people. The health ministries are now interested in the data previously collected on these irradiated populations in order to examine the health (e.g., psychological, hereditary, genome damage, etc.) implications of long-term radiation exposure.

  7. Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma

    PubMed Central

    DEQUANTER, DIDIER; VAN DE VELDE, MAUREEN; BAR, ISABELLE; NUYENS, VINCENT; ROUSSEAU, ALEXANDRE; NAGY, NATHALIE; VANHAMME, LUC; VANHAEVERBEEK, MICHEL; BROHÉE, DANY; DELRÉE, PAUL; BOUDJELTIA, KARIM; LOTHAIRE, PHILIPPE; UZUREAU, PIERRICK

    2016-01-01

    Glutathione (GSH) is the keystone of the cellular response toward oxidative stress. Elevated GSH content correlates with increased resistance to chemotherapy and radiotherapy of head and neck (HN) tumors. The purpose of the present cross-sectional study was to evaluate whether the expression of glutamate-cysteine ligase (GCL) accounts for the increased GSH availability observed in HN squamous cell carcinoma (SCC). For that purpose, the messenger (m)RNA levels of the modifier (M) and catalytic (C) subunits of GCL and its putative regulators (namely, nuclear factor erythroid 2-related factor 2, heme oxygenase-1 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) were monitored in 35 surgical resections of untreated HNSCC. The localization of GCLM was evaluated using in situ hybridization and immunohistochemistry. GCLM expression was significantly increased in tumor samples, compared with normal mucosa, both at the mRNA and protein level (P=0.029), but the pathway of GCLM activation remains to be elucidated. Protein expression of GCLM was detected in the cytoplasm and nucleus. GCLM and the proliferation marker Ki-67 displayed a similar distribution, being both mainly expressed at the periphery of tumor lobules. The present study reported increased expression of GCL and the rate-limiting enzyme of GSH synthesis, within HNSCC. The nuclear localization of GCLM and the concomitant expression of Ki-67 suggested that the localization of GSH synthesis contributes to the protection against oxidative stress within hotspots of cell proliferation. PMID:27284370

  8. 36th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2015 annual meeting.

    PubMed

    Gripp, Karen W; Adam, Margaret P; Hudgins, Louanne; Carey, John C

    2016-07-01

    The 36th Annual David W Smith Workshop on Malformations and Morphogenesis was held on August 14-19, 2015 at the Harbourtowne Conference Center in St. Michaels Maryland. The Workshop, which honors the legacy of David W Smith, brought together over 120 clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. As is the tradition of the meeting, the Workshop highlighted five themes besides mechanisms of morphogenesis: Rasopathies, Eye Malformations, Therapeutics, Prenatal Diagnosis, and Disorders of Sex Development. This Conference Report includes the abstracts presented at the 2015 Workshop. © 2016 Wiley Periodicals, Inc.

  9. FUS interacts with nuclear matrix-associated protein SAFB1 as well as Matrin3 to regulate splicing and ligand-mediated transcription

    PubMed Central

    Yamaguchi, Atsushi; Takanashi, Keisuke

    2016-01-01

    FUS (Fused-in-Sarcoma) is a multifunctional DNA/RNA binding protein linked to familial amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). Since FUS is localized mainly in the nucleus with nucleo-cytoplasmic shuttling, it is critical to understand physiological functions in the nucleus to clarify pathogenesis. Here we report a yeast two-hybrid screening identified FUS interaction with nuclear matrix-associated protein SAFB1 (scaffold attachment factor B1). FUS and SAFB1, abundant in chromatin-bound fraction, interact in a DNA-dependent manner. N-terminal SAP domain of SAFB1, a DNA-binding motif, was required for its localization to chromatin-bound fraction and splicing regulation. In addition, depletion of SAFB1 reduced FUS’s localization to chromatin-bound fraction and splicing activity, suggesting SAFB1 could tether FUS to chromatin compartment thorough N-terminal DNA-binding motif. FUS and SAFB1 also interact with Androgen Receptor (AR) regulating ligand-dependent transcription. Moreover, FUS interacts with another nuclear matrix-associated protein Matrin3, which is muted in a subset of familial ALS cases and reportedly interacts with TDP-43. Interestingly, ectopic ALS-linked FUS mutant sequestered endogenous Matrin3 and SAFB1 in the cytoplasmic aggregates. These findings indicate SAFB1 could be a FUS’s functional platform in chromatin compartment to regulate RNA splicing and ligand-dependent transcription and shed light on the etiological significance of nuclear matrix-associated proteins in ALS pathogenesis. PMID:27731383

  10. Implications of the sedimentology and isotope geochemistry of calcic horizons in the Pliocene-Early Pleistocene St. David Fm. , Arizona

    SciTech Connect

    Smith, G.A. . Dept. of Earth and Planetary Science); Wang, Y.; Cerling, T.E. )

    1992-01-01

    Two types of calcic horizons occur in pedogenically modified alluvial mudstones of the Plio-Pleistocene St. David Fm.: (1) nodular-carbonate zones (stage 2 morphology) with downward decreasing carbonate abundance, located below leached red muds; (2) massive to nodular zones (stage 3) with sharp bases, upward decrease in carbonate abundance, associated with variably leached muds typically exhibiting green mottles. Type 1 horizons are traceable for hundreds of meters; type 2 horizons vary in thickness and carbonate content over distances as short at 15 m. and are laterally contiguous with pond deposits. Type 1 horizons are interpreted as vadose aridosol calcic horizons, whereas type 2 horizons are partly gleyed hydromorphic soils with calcite derived from groundwater as well as from leaching within the soil. O and C isotopic compositions of age-equivalent 1 and 2 carbonates are similar suggesting that type 2 calcite formed in the unsaturated zone, probably in the capillary fringe above the water table. These latter horizons define a limited time of elevated water table, which corresponds to a cooler/wetter climate and higher sedimentation rates. If the distinction between these two soil types was not made, the greater morphological maturity'' of type 2 horizons would lead to misinterpretation of more arid climatic conditions or lower sedimentation rates. Type 1 horizons occur within parallel piedmont-facies belts representing channel/channel margin and floodplain deposition. Paleosols are morphologically similar, although floodplain soils are more clay rich. C-isotope analyses suggest, however, different vegetational histories for the two depositional tracts that reflect different responses of channel-margin and floodplain settings to increasing seasonality of precipitation during the late Pliocene.

  11. A Novel Toxoplasma gondii Nuclear Factor TgNF3 Is a Dynamic Chromatin-Associated Component, Modulator of Nucleolar Architecture and Parasite Virulence

    PubMed Central

    Olguin-Lamas, Alejandro; Madec, Edwige; Hovasse, Agnes; Werkmeister, Elisabeth; Callebaut, Isabelle; Slomianny, Christian; Delhaye, Stephane; Mouveaux, Thomas; Schaeffer-Reiss, Christine; Van Dorsselaer, Alain; Tomavo, Stanislas

    2011-01-01

    In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP), known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating nucleosome

  12. EDITORIAL: Van der Waals interactions in advanced materials, in memory of David C Langreth Van der Waals interactions in advanced materials, in memory of David C Langreth

    NASA Astrophysics Data System (ADS)

    Hyldgaard, Per; Rahman, Talat S.

    2012-10-01

    sufficiently close to any corrugated—and/or any smooth—surface and thus enforce a strong vdW-type adhesion; it exploits what is then essentially a contact force (dominated by the attraction exerted in the near-surface regions) to defy the pull of gravity on its own bulk. This Journal of Physics: Condensed Matter special issue is dedicated to the memory of David C Langreth. David is a dearly missed friend and mentor who inspired many of us. He was an outstanding condensed matter theorist and a scholar who greatly influenced us through his many-particle-physics based insights into density functional theory (DFT), surface science and related areas. His seminal works range from conserving formulations of interacting nonequilibrium transport [1] and formal-scattering theory [2] to an explicit formulation [3] of the exact DFT exchange-correlation energy in the adiabatic connection formula (ACF), the latter also being derived independently by Gunnarsson and Lundqvist [4]. David's portfolio also includes an analysis [5] that helped catalyze and guide the development of DFT from the local-density approximation (LDA) to the formulations of generalized gradient approximations (GGAs). Another salient contribution of David's is in the area of vdW interactions in materials. He was a key architect of the vdW density functional (vdW-DF) method [6, 7]. This method was developed in a long-standing Rutgers-Chalmers collaboration between David's group and that of Bengt I Lundqvist, later extending to a wider group of researchers on both sides of the Atlantic. Plasmons are collective excitations that depend on electron-density variation. The plasmon response can be seen as defining the nature of the LDA [4] and their description can thus also be seen as contributing to the success of GGA. The vdW-DF method is a regular constraint-based density functional (for ground-state DFT) which is derived within the ACF framework and which emphasizes the electrodynamical nature of the coupling between

  13. NASA astronaut and Mir 24 crew member David Wolf after landing

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA astronaut and Mir 24 crew member David Wolf, M.D., who was on the Russian Space Station Mir since late September 1997, greets his friend, Tammy Kruse, shortly after his return to Earth on Jan. 31. Dr. Wolf returned aboard the orbiter Endeavour with the rest of the STS-89 crew, including Commander Terrence Wilcutt; Pilot Joe Edwards Jr.; and Mission Specialists James Reilly, Ph.D.; Michael Anderson; Bonnie Dunbar, Ph.D.; and Salizhan Sharipov with the Russian Space Agency. STS-89 Mission Specialist Andrew Thomas, Ph.D., succeeded Dr. Wolf on Mir and is scheduled to remain on the Russian space station until the STS-91 Shuttle mission returns in June 1998. In addition to the docking and crew exchange, STS-89 included the transfer of science, logistical equipment and supplies between the two orbiting spacecrafts.

  14. Work plan for the radiological survey for the David Witherspoon, Incorporated, Landfill-1630 site, Knoxville, Tennessee

    SciTech Connect

    1996-07-01

    This work plan establishes the methods and requirements for performing a radiological survey at the David Witherspoon, Incorporated, Landfill-1630 Site, Knoxville, Tennessee (DWI 1630 Site) in accordance with requirements under the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA). The radiological survey will identify the radiological contamination level of the equipment and debris stored at the DWI 1630 Site. The data generated from the survey activities will support the decisions for characterization of the equipment/debris and aid in subsequent disposition and waste handling. The survey activities to be performed under this work plan include an equipment radiological survey, a walkover survey, and an immunoassay testing for polychlorinated biphenyls (PCBs). This work plan includes a quality assurance (QA)/quality control (QC) project plan, a health and safety (H&S) plan, and a waste management plan.

  15. Astronaut David Brown talks with team members from Lake Buena Vista, Fla

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Astronaut David Brown chats with members of the Explorers team, from Lake Buena Vista, Fla., during the FIRST (For Inspiration and Recognition of Science and Technology) Southeast Regional competition held March 9-11 in the KSC Visitor Complex Rocket Garden. Teams of high school students from all over the country are testing the limits of their imagination using robots they have designed, with the support of business and engineering professionals and corporate sponsors, to compete in a technological battle against other schools' robots. Of the 30 high school teams competing at the Southeast Regional event, 16 are Florida teams co-sponsored by NASA and KSC contractors. Local high schools participating are Astronaut, Bayside, Cocoa Beach, Eau Gallie, Melbourne, Melbourne Central Catholic, Palm Bay, Rockledge, Satellite, and Titusville.

  16. The reconstitution of political theory: David Easton, behavioralism, and the long road to system.

    PubMed

    Gunnell, John G

    2013-01-01

    During the last half of the twentieth century, the concept of system was arguably the most important concept in the theoretical repertoire of the discipline of American political science. Although systems analysis was broadly employed in the behavioral sciences, David Easton's work was particularly influential in the study of politics. This is in part because he attempted to develop a distinct account of the political system that was not theoretically subservient either to general systems theory or to conceptions of the social system such as that advanced by Talcott Parsons. Although a great deal of attention has been devoted to Easton's theory, the origins and evolution of the system concept in his work have not been carefully reconstructed and analyzed. PMID:23423865

  17. Remedial investigation/feasibility study for the David Witherspoon, Inc., 901 Site, Knoxville, Tennessee: Volume 1

    SciTech Connect

    1996-10-01

    This remedial investigation (RI)/feasibility study (FS) supports the selection of remedial actions for the David Witherspoon, Inc. 901 Maryville Pike Site in Knoxville, Tennessee. Operations at the site, used as a recycling center, have resulted in past, present, and potential future releases of hazardous substances in to the environment. This Site is a Tennessee Superfund site. A phased approach was planned to (1) gather existing data from previous investigations managed by the Tenn. Dept. of Environment and Conservation; (2) perform a preliminary RI, including risk assessments, and an FS with existing data to identify areas where remedial action may be necessary; (3) gather additional field data to adequately define the nature and extent of risk-based contaminants that present identifiable threats to human and/or ecological receptors; and (4) develop remedial action alternatives to reduce risks to acceptable levels.

  18. The David Jayne amendment: the story of one man's determination to improve the lives of thousands.

    PubMed

    Sokol, Eric

    2003-09-01

    Stricken by ALS at the age of 27, David Jayne slowly lost the ability to walk, to eat, to speak, and to breathe. With the assistance of home health professionals, medical technologies, and volunteers, he has managed to maintain as full a life as possible, participating in some of his children's activities and even managing, with great effort, to attend a football game. However, when he was the subject of a newspaper article, his home health coverage was dropped because he didn't meet the federal definition of "homebound." This is the story of how he took on the political establishment single-handedly, and eventually realized a victory that has the potential of helping thousands of people in similar situations to no longer be imprisoned at home. PMID:14618902

  19. Association of Nuclear PIM1 Expression with Lymph Node Metastasis and Poor Prognosis in Patients with Lung Adenocarcinoma and Squamous Cell Carcinoma

    PubMed Central

    Jiang, Richeng; Wang, Xinyue; Jin, Ziliang; Li, Kai

    2016-01-01

    Increasing evidence indicates that aberrant expression of PIM1, p-STAT3 and c-MYC is involved in the pathogenesis of various solid tumors, but its prognostic value is still unclear in non-small cell lung cancer (NSCLC). Here, we sought to evaluate the expression and prognostic role of these markers in patients with lung adenocarcinoma (AD) and squamous cell carcinoma (SCC). Real time RT-PCR and Western blotting was used to analyze the mRNA and protein expression of PIM1 in NSCLC cell lines, respectively. The expression of PIM1, p-STAT3, and c-MYC was immunohistochemically tested in archival tumor samples from 194 lung AD and SCC patients. High nuclear PIM1 expression was detected in 43.3% of ADs and SCCs, and was significantly correlated with lymph node (LN) metastasis (P = 0.028) and histology (P = 0.003). High nuclear PIM1 expression (P = 0.034), locally advanced stage (P < 0.001), AD (P = 0.007) and poor pathologic differentiation (P = 0.002) were correlated with worse disease-free survival (DFS). High nuclear PIM1 expression (P = 0.009), advanced clinical stage (P < 0.001) and poor pathologic differentiation (P = 0.004) were independent unfavorable prognostic factors for overall survival (OS). High p-STAT3 expression was not associated with OS but significantly correlated with LN metastasis, while c-MYC was not significantly correlated with any clinicopathological parameter or survival. Therefore, in AD and SCC patients, nuclear PIM1 expression level is an independent factor for DFS and OS and it might serve as a predictive biomarker for outcome. PMID:26918046

  20. Nuclear Nonproliferation

    SciTech Connect

    Atkins-Duffin, C E

    2008-12-10

    With an explosion equivalent of about 20kT of TNT, the Trinity test was the first demonstration of a nuclear weapon. Conducted on July 16, 1945 in Alamogordo, NM this site is now a Registered National Historic Landmark. The concept and applicability of nuclear power was demonstrated on December 20, 1951 with the Experimental Breeder Reactor Number One (EBR-1) lit four light bulbs. This reactor is now a Registered National Historic Landmark, located near Arco, ID. From that moment forward it had been clearly demonstrated that nuclear energy has both peaceful and military applications and that the civilian and military fuel cycles can overlap. For the more than fifty years since the Atoms for Peace program, a key objective of nuclear policy has been to enable the wider peaceful use of nuclear energy while preventing the spread of nuclear weapons. Volumes have been written on the impact of these two actions on the world by advocates and critics; pundits and practioners; politicians and technologists. The nations of the world have woven together a delicate balance of treaties, agreements, frameworks and handshakes that are representative of the timeframe in which they were constructed and how they have evolved in time. Collectively these vehicles attempt to keep political will, nuclear materials and technology in check. This paper captures only the briefest abstract of the more significant aspects on the Nonproliferation Regime. Of particular relevance to this discussion is the special nonproliferation sensitivity associated with the uranium isotope separation and spent fuel reprocessing aspects of the nuclear fuel cycle.

  1. A review of literature pertaining to the leaching and sorption of radionuclides associated with nuclear explosive melt glasses

    SciTech Connect

    Smith, D.K.

    1993-05-01

    For the purposes of groundwater characterization, environmental remediation and health risk assessment, the mechanism and rate by which radionuclides bound within nuclear device melt glass are manifest in Nevada Test Site groundwaters must be known. Exchange between radionuclides and groundwater is dominated by the kinetics of leaching and the resultant sorption of derivative nuclides by minerals along the flow-path. In this context, a survey of the report literature has been conducted to review work related to these subjects. This report provides a representative, although not exhaustive, summary of the literature; because of the specialized nature of nuclear melt glass, emphasis was given to the report literature available from Lawrence Livermore and Los Alamos National Laboratories, the Department of Energy and its predecessor agencies and pertinent contractors. Where data is corroborated in journal literature, those references are also included. Before the risk to ground waters is estimated with any accuracy, recommendations for continued future work integrate systematic characterization of melt glass with leaching studies of these heterogeneous matrices.

  2. Population Polymorphism of Nuclear Mitochondrial DNA Insertions Reveals Widespread Diploidy Associated with Loss of Heterozygosity in Debaryomyces hansenii ▿ †

    PubMed Central

    Jacques, Noémie; Sacerdot, Christine; Derkaoui, Meriem; Dujon, Bernard; Ozier-Kalogeropoulos, Odile; Casaregola, Serge

    2010-01-01

    Debaryomyces hansenii, a yeast that participates in the elaboration of foodstuff, displays important genetic diversity. Our recent phylogenetic classification of this species led to the subdivision of the species into three distinct clades. D. hansenii harbors the highest number of nuclear mitochondrial DNA (NUMT) insertions known so far for hemiascomycetous yeasts. Here we assessed the intraspecific variability of the NUMTs in this species by testing their presence/absence first in 28 strains, with 21 loci previously detected in the completely sequenced strain CBS 767T, and second in a larger panel of 77 strains, with 8 most informative loci. We were able for the first time to structure populations in D. hansenii, although we observed little NUMT insertion variability within the clades. We determined the chronology of the NUMT insertions, which turned out to correlate with the previously defined taxonomy and provided additional evidence that colonization of nuclear genomes by mitochondrial DNA is a dynamic process in yeast. In combination with flow cytometry experiments, the NUMT analysis revealed the existence of both haploid and diploid strains, the latter being heterozygous and resulting from at least four crosses among strains from the various clades. As in the diploid pathogen Candida albicans, to which D. hansenii is phylogenetically related, we observed a differential loss of heterozygosity in the diploid strains, which can explain some of the large genetic diversity found in D. hansenii over the years. PMID:20048048

  3. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGK{zeta} by attenuating its association with importins

    SciTech Connect

    Okada, Masashi; Hozumi, Yasukazu; Ichimura, Tohru; Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya; Iseki, Ken; Yagisawa, Hitoshi; Shinkawa, Takashi; Isobe, Toshiaki; Goto, Kaoru

    2011-12-10

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGK{zeta}, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGK{zeta}. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGK{zeta} binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGK{zeta} and NAP1Ls prohibits nuclear import of DGK{zeta} because binding of NAP1Ls to DGK{zeta} blocks import carrier proteins, Qip1 and NPI1, to interact with DGK{zeta}, leading to cytoplasmic tethering of DGK{zeta}. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGK{zeta} and provide a clue to examine functional significance of its translocation under pathological conditions.

  4. Association of Nuclear Factor-Erythroid 2-Related Factor 2, Thioredoxin Interacting Protein, and Heme Oxygenase-1 Gene Polymorphisms with Diabetes and Obesity in Mexican Patients

    PubMed Central

    Jiménez-Osorio, Angélica Saraí; González-Reyes, Susana; García-Niño, Wylly Ramsés; Moreno-Macías, Hortensia; Rodríguez-Arellano, Martha Eunice; Vargas-Alarcón, Gilberto; Zúñiga, Joaquín; Barquera, Rodrigo; Pedraza-Chaverri, José

    2016-01-01

    The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H:quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, P = 0.005) and in women (CC versus CT + TT, OR = 0.7, P = 0.016). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, P = 0.026). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, P = 0.003). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients. PMID:27274779

  5. RFHVMn ORF73 is structurally related to the KSHV ORF73 latency-associated nuclear antigen (LANA) and is expressed in retroperitoneal fibromatosis (RF) tumor cells

    SciTech Connect

    Burnside, Kellie L.; Ryan, Jonathan T.; Bielefeldt-Ohmann, Helle; Gregory Bruce, A.; Thouless, Margaret E.; Tsai, Che-Chung; Rose, Timothy M. . E-mail: trose@u.washington.edu

    2006-10-10

    Retroperitoneal fibromatosis herpesvirus (RFHV), the macaque homolog of the human rhadinovirus, Kaposi's sarcoma-associated herpesvirus (KSHV), was first identified in retroperitoneal fibromatosis (RF) tumor lesions of macaques with simian AIDS. We cloned and sequenced the ORF73 latency-associated nuclear antigen (LANA) of RFHVMn from the pig-tailed macaque. RFHVMn LANA is structurally analogous to KSHV ORF73 LANA and contains an N-terminal serine-proline-rich region, a large internal glutamic acidic-rich repeat region and a conserved C-terminal domain. RFHVMn LANA reacts with monoclonal antibodies specific for a glutamic acid-proline dipeptide motif and a glutamic acid-glutamine-rich motif in the KSHV LANA repeat region. Immunohistochemical and immunofluorescence analysis revealed that RFHVMn LANA is a nuclear antigen which is highly expressed in RF spindloid tumor cells. These data suggest that RFHV LANA is an ortholog of KSHV LANA and will function similarly to maintain viral latency and play a role in tumorigenicity in macaques.

  6. Production of CFTR-null and CFTR-ΔF508 heterozygous pigs by adeno-associated virus–mediated gene targeting and somatic cell nuclear transfer

    PubMed Central

    Rogers, Christopher S.; Hao, Yanhong; Rokhlina, Tatiana; Samuel, Melissa; Stoltz, David A.; Li, Yuhong; Petroff, Elena; Vermeer, Daniel W.; Kabel, Amanda C.; Yan, Ziying; Spate, Lee; Wax, David; Murphy, Clifton N.; Rieke, August; Whitworth, Kristin; Linville, Michael L.; Korte, Scott W.; Engelhardt, John F.; Welsh, Michael J.; Prather, Randall S.

    2008-01-01

    Progress toward understanding the pathogenesis of cystic fibrosis (CF) and developing effective therapies has been hampered by lack of a relevant animal model. CF mice fail to develop the lung and pancreatic disease that cause most of the morbidity and mortality in patients with CF. Pigs may be better animals than mice in which to model human genetic diseases because their anatomy, biochemistry, physiology, size, and genetics are more similar to those of humans. However, to date, gene-targeted mammalian models of human genetic disease have not been reported for any species other than mice. Here we describe the first steps toward the generation of a pig model of CF. We used recombinant adeno-associated virus (rAAV) vectors to deliver genetic constructs targeting the CF transmembrane conductance receptor (CFTR) gene to pig fetal fibroblasts. We generated cells with the CFTR gene either disrupted or containing the most common CF-associated mutation (ΔF508). These cells were used as nuclear donors for somatic cell nuclear transfer to porcine oocytes. We thereby generated heterozygote male piglets with each mutation. These pigs should be of value in producing new models of CF. In addition, because gene-modified mice often fail to replicate human diseases, this approach could be used to generate models of other human genetic diseases in species other than mice. PMID:18324337

  7. "And This Is How You Shall Ask": Linguistics, Anthropology, and Education in the Work of David Smith

    ERIC Educational Resources Information Center

    Gilmore, Perry; McDermott, Ray

    2006-01-01

    This article celebrates the life and work of David M. Smith, former Council on Anthropology and Education president and founder of the University of Pennsylvania Ethnography in Education Research Forum, tracing his contributions to the fields of linguistics, anthropology, and education through the dual lens of his ten research principles and Walt…

  8. Constructing the Image of Authorial Presence: David O. Selznick and the Marketing of "Since You Went Away."

    ERIC Educational Resources Information Center

    Fenster, Mark

    1989-01-01

    Analyzes David O. Selznick's marketing campaign for the film "Since You Went Away," focusing on the promotion of the book from which the movie was adapted, and on the production of the film's souvenir program. Examines Selznick's image as author from both the auteurist and cine-structuralist perspectives. (MM)

  9. Teaching Family Communication Concepts through Family Stories: An Analysis of Stories and Rituals in David Bradley's "Harvest Home"

    ERIC Educational Resources Information Center

    Dixson, Marcia D.

    2006-01-01

    In this activity, students will be able to apply the concepts of stories and rituals to an analysis of the ritual in the short story "Harvest Home" by David Bradley, gaining understanding of how stories and rituals affect and reflect family values, power structures and identities. "Harvest Home" talks about the rituals involved in a…

  10. Theorising "Geo-Identity" and David Harvey's Space: School Choices of the Geographically Bound Middle-Class

    ERIC Educational Resources Information Center

    Rowe, Emma

    2015-01-01

    This paper draws on David Harvey's theories of absolute and relational space in order to critique geographically bound school choices of the gentrified middle-class in the City of Melbourne, Australia. The paper relies on interviews with inner-city school choosers as generated by a longitudinal ethnographic school choice study. I argue that the…

  11. Preserving Precious Instruments in Mathematics History: The Educational Museum of Teachers College and David Eugene Smith's Collection

    ERIC Educational Resources Information Center

    Murray, Diane R.

    2011-01-01

    A history is given of the Educational Museum of Teachers College, which began in 1886, and David Eugene Smith's extensive collection of mathematical tools used in the Museum's exhibits is discussed. Historic mathematical instruments including, the astrolabe, abacus and counting rods, and the slide rule are examined. The author uses digitized…

  12. Salvaging "Academic Disaster Areas": The Black College Response to Christopher Jencks and David Riesman's 1967 Harvard Educational Review Article

    ERIC Educational Resources Information Center

    Gasman, Marybeth

    2006-01-01

    In 1967, the "Harvard Educational Review" published an article entitled "The American Negro College" by Christopher Jencks and David Riesman. The article dealt a stinging blow to Black colleges--labeling them "academic disaster areas." Using a historical methodology, I show the strategic ways in which Black college leaders and the United Negro…

  13. A Philosophical Analysis of David Orr's Theory of Ecological Literacy: Biophilia, Ecojustice and Moral Education in School Learning Communities

    ERIC Educational Resources Information Center

    Mitchell, Debra B.; Mueller, Michael P.

    2011-01-01

    In his writings, David Orr claims that the US is in an "ecological crisis" and that this stems from a crisis of education. He outlines a theory of ecological literacy, a mode by which we better learn the ecology of the Earth and live in a sustainable manner. While emphasizing a shock doctrine, the diagnosis of "crisis" may be correct, but it is…

  14. Measuring Success: David Conley's College Readiness Framework and the Illinois College and Career Readiness Act. In Brief

    ERIC Educational Resources Information Center

    Baber, Lorenzo D.; Castro, Erin L.; Bragg, Debra D.

    2010-01-01

    The purpose of this brief is to understand the Illinois College and Career Readiness (CCR) Act in light of David Conley's college readiness model. Although not mentioned specifically by the Illinois statute, evaluation results gathered by the Office of Community College Research and Leadership (OCCRL) show alignment between a number of programs…

  15. The Eclipse of the Public: A Response to David Elliott's "Music Education as/for Artistic Citizenship"

    ERIC Educational Resources Information Center

    Woodford, Paul

    2014-01-01

    This paper is an invited response to a one published by David Elliott in The Music Educator in 2012 in which music teachers were enjoined to encourage children to use music's expressive power as a political tool in pursuit of social justice. While in agreement with him that this can be an appropriate use of music, there is a curious avoidance…

  16. Teacher as Actor--Henry David Thoreau--From Room One-Eleven to Walden Pond and Beyond.

    ERIC Educational Resources Information Center

    Barto, David

    To help maintain class interest in the important themes addressed in "Walden" and "The Duties of Civil Disobedience," a high school English teacher has presented a dramatic monologue as Henry David Thoreau to his students. After much library research, the teacher used some of the props characteristic of the author, such as a walking stick and a…

  17. The Repositioning of Language Centres: An Appreciation of David Ingram's "Language Centres--Their Roles, Functions and Management"

    ERIC Educational Resources Information Center

    Sussex, Roland

    2004-01-01

    David Ingram's "Language Centres" (2001) offers a descriptive and analytical study of meta-centres, their constitution, operation and engagement with their constituencies. This article is a combination of a review and an appreciation of Ingram's study, and--benefiting from the latitude offered by the genre of the review article--a set of…

  18. Rate, Probability and Matching: Comments on "The Identities Hidden in the Matching Laws, and Their Uses" by David Thorne

    ERIC Educational Resources Information Center

    Rachlin, Howard; Locey, Matthew L.

    2010-01-01

    David Thorne's (2010) article, "The Identities Hidden In The Matching Laws, And Their Uses" performs a valuable service in pointing out alternative expressions of matching. However, some identities tend to obscure rather than illuminate empirical relationships. Three such problematic instances are discussed: interresponse time as a function of…

  19. Values, Leadership, and Quality: The Administration of Higher Education. The David D. Henry Lectures, 1979-1985.

    ERIC Educational Resources Information Center

    1990

    This book contains five lectures, delivered as part of the David D. Henry lecture series, whose common theme revolved around broadly defined issues related to the administration of higher education. The first lecture, "Quality and Equality in Health Professions Education and Service" (Lloyd C. Elam), argues that quality and equality in the…

  20. Limited internal radiation exposure associated with resettlements to a radiation-contaminated homeland after the Fukushima Daiichi nuclear disaster.

    PubMed

    Tsubokura, Masaharu; Kato, Shigeaki; Nihei, Masahiko; Sakuma, Yu; Furutani, Tomoyuki; Uehara, Keisuke; Sugimoto, Amina; Nomura, Shuhei; Hayano, Ryugo; Kami, Masahiro; Watanobe, Hajime; Endo, Yukou

    2013-01-01

    Resettlement to their radiation-contaminated hometown could be an option for people displaced at the time of a nuclear disaster; however, little information is available on the safety implications of these resettlement programs. Kawauchi village, located 12-30 km southwest of the Fukushima Daiichi nuclear power plant, was one of the 11 municipalities where mandatory evacuation was ordered by the central government. This village was also the first municipality to organize the return of the villagers. To assess the validity of the Kawauchi villagers' resettlement program, the levels of internal Cesium (Cs) exposures were comparatively measured in returnees, commuters, and non-returnees among the Kawauchi villagers using a whole body counter. Of 149 individuals, 5 villagers had traceable levels of Cs exposure; the median detected level was 333 Bq/body (range, 309-1050 Bq/kg), and 5.3 Bq/kg (range, 5.1-18.2 Bq/kg). Median annual effective doses of villagers with traceable Cs were 1.1 x 10(-2) mSv/y (range, 1.0 x 10(-2)-4.1 x 10(-2) mSv/y). Although returnees had higher chances of consuming locally produced vegetables, Cochran-Mantel-Haenszel test showed that their level of internal radiation exposure was not significantly higher than that in the other 2 groups (p=0.643). The present findings in Kawauchi village imply that it is possible to maintain internal radiation exposure at very low levels even in a highly radiation-contaminated region at the time of a nuclear disaster. Moreover, the risks for internal radiation exposure could be limited with a strict food control intervention after resettlement to the radiation-contaminated village. It is crucial to establish an adequate number of radio-contaminated testing sites within the village, to provide immediate test result feedback to the villagers, and to provide education regarding the importance of re-testing in reducing the risk of high internal radiation exposure.

  1. Limited Internal Radiation Exposure Associated with Resettlements to a Radiation-Contaminated Homeland after the Fukushima Daiichi Nuclear Disaster

    PubMed Central

    Tsubokura, Masaharu; Kato, Shigeaki; Nihei, Masahiko; Sakuma, Yu; Furutani, Tomoyuki; Uehara, Keisuke; Sugimoto, Amina; Nomura, Shuhei; Hayano, Ryugo; Kami, Masahiro; Watanobe, Hajime; Endo, Yukou

    2013-01-01

    Resettlement to their radiation-contaminated hometown could be an option for people displaced at the time of a nuclear disaster; however, little information is available on the safety implications of these resettlement programs. Kawauchi village, located 12–30 km southwest of the Fukushima Daiichi nuclear power plant, was one of the 11 municipalities where mandatory evacuation was ordered by the central government. This village was also the first municipality to organize the return of the villagers. To assess the validity of the Kawauchi villagers’ resettlement program, the levels of internal Cesium (Cs) exposures were comparatively measured in returnees, commuters, and non-returnees among the Kawauchi villagers using a whole body counter. Of 149 individuals, 5 villagers had traceable levels of Cs exposure; the median detected level was 333 Bq/body (range, 309–1050 Bq/kg), and 5.3 Bq/kg (range, 5.1–18.2 Bq/kg). Median annual effective doses of villagers with traceable Cs were 1.1 x 10-2 mSv/y (range, 1.0 x 10-2-4.1 x 10-2 mSv/y). Although returnees had higher chances of consuming locally produced vegetables, Cochran-Mantel-Haenszel test showed that their level of internal radiation exposure was not significantly higher than that in the other 2 groups (p=0.643). The present findings in Kawauchi village imply that it is possible to maintain internal radiation exposure at very low levels even in a highly radiation-contaminated region at the time of a nuclear disaster. Moreover, the risks for internal radiation exposure could be limited with a strict food control intervention after resettlement to the radiation-contaminated village. It is crucial to establish an adequate number of radio-contaminated testing sites within the village, to provide immediate test result feedback to the villagers, and to provide education regarding the importance of re-testing in reducing the risk of high internal radiation exposure. PMID:24312602

  2. Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import*

    PubMed Central

    Di Lascio, Simona; Belperio, Debora

    2016-01-01

    Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity. PMID:27129232

  3. Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

    PubMed Central

    2011-01-01

    Introduction In the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry. Methods Sera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion. Results Antinuclear antibodies (ANA) were detected in 94.2% of patients. In 81.6%, at least one of the autoantibodies highly associated with SSc or with overlap syndromes with scleroderma features was detected, that is, anti-centromere (35.9%) or anti-topoisomerase I (30.1%), followed in markedly lower frequency by antibodies to PM-Scl (4.9%), U1-ribonucleoprotein (U1-RNP) (4.8%), RNA polymerases (RNAPs) (3.8%), fibrillarin (1.4%), Ku (1.2%), aminoacyl-transfer RNA synthetases (0.5%), To (0.2%) and U11-RNP (0.1%). We found that the simultaneous presence of SSc-associated autoantibodies was rare (1.6%). Furthermore, additional autoantibodies were detected in 55.4% of the patients with SSc, of which anti-Ro/anti-La, anti-mitochondrial and anti-p25/p23 antibodies were most frequent. The coexistence of SSc-associated and other autoantibodies was common (43% of patients). SSc-associated autoantibodies disclosed characteristic associations with clinical features of patients, some of which were previously not acknowledged. Conclusions This study shows that five autoantigens (that is, centromere, topoisomerase I, PM-Scl, U1-RNP and RNAP) detected more than 95% of the known SSc-associated antibody responses in ANA-positive SSc patients and characterise around 79% of all SSc patients in a central European cohort. These data confirm and extend previous data underlining the central role of the determination of ANAs in defining the diagnosis, subset allocation and prognosis of SSc patients. PMID:22018289

  4. Nuclear Medicine

    MedlinePlus

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  5. Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma tumor formation in NOD/SCID mice is inhibited by neomycin and neamine blocking angiogenin's nuclear translocation.

    PubMed

    Bottero, Virginie; Sadagopan, Sathish; Johnson, Karen E; Dutta, Sujoy; Veettil, Mohanan Valiya; Chandran, Bala

    2013-11-01

    Angiogenin (ANG) is a 14-kDa multifunctional proangiogenic secreted protein whose expression level correlates with the aggressiveness of several tumors. We observed increased ANG expression and secretion in endothelial cells during de novo infection with Kaposi's sarcoma-associated herpesvirus (KSHV), in cells expressing only latency-associated nuclear antigen 1 (LANA-1) protein, and in KSHV latently infected primary effusion lymphoma (PEL) BCBL-1 and BC-3 cells. Inhibition of phospholipase Cγ (PLCγ) mediated ANG's nuclear translocation by neomycin, an aminoglycoside antibiotic (not G418-neomicin), resulted in reduced KSHV latent gene expression, increased lytic gene expression, and increased cell death of KSHV(+) PEL and endothelial cells. ANG detection in significant levels in KS and PEL lesions highlights its importance in KSHV pathogenesis. To assess the in vivo antitumor activity of neomycin and neamine (a nontoxic derivative of neomycin), BCBL-1 cells were injected intraperitoneally into NOD/SCID mice. We observed significant extended survival of mice treated with neomycin or neamine. Markers of lymphoma establishment, such as increases in animal body weight, spleen size, tumor cell spleen infiltration, and ascites volume, were observed in nontreated animals and were significantly diminished by neomycin or neamine treatments. A significant decrease in LANA-1 expression, an increase in lytic gene expression, and an increase in cleaved caspase-3 were also observed in neomycin- or neamine-treated animal ascitic cells. These studies demonstrated that ANG played an essential role in KSHV latency maintenance and BCBL-1 cell survival in vivo, and targeting ANG function by neomycin/neamine to induce the apoptosis of cells latently infected with KSHV is an attractive therapeutic strategy against KSHV-associated malignancies.

  6. Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer.

    PubMed

    Edwards, J L; Schrick, F N; McCracken, M D; van Amstel, S R; Hopkins, F M; Welborn, M G; Davies, C J

    2003-08-01

    In 1997, Wilmut et al. announced the birth of Dolly, the first ever clone of an adult animal. To date, adult sheep, goats, cattle, mice, pigs, cats and rabbits have been cloned using somatic cell nuclear transfer. The ultimate challenge of cloning procedures is to reprogram the somatic cell nucleus for development of the early embryo. The cell type of choice for reprogramming the somatic nucleus is an enucleated oocyte. Given that somatic cells are easily obtained from adult animals, cultured in the laboratory and then genetically modified, cloning procedures are ideal for introducing specific genetic modifications in farm animals. Genetic modification of farm animals provides a means of studying genes involved in a variety of biological systems and disease processes. Moreover, genetically modified farm animals have created a new form of 'pharming' whereby farm animals serve as bioreactors for production of pharmaceuticals or organ donors. A major limitation of cloning procedures is the extreme inefficiency for producing live offspring. Dolly was the only live offspring produced after 277 attempts. Similar inefficiencies for cloning adult animals of other species have been described by others. Many factors related to cloning procedures and culture environment contribute to the death of clones, both in the embryonic and fetal periods as well as during neonatal life. Extreme inefficiencies of this magnitude, along with the fact that death of the surrogate may occur, continue to raise great concerns with cloning humans.

  7. Cloning adult farm animals: a review of the possibilities and problems associated with somatic cell nuclear transfer.

    PubMed

    Edwards, J L; Schrick, F N; McCracken, M D; van Amstel, S R; Hopkins, F M; Welborn, M G; Davies, C J

    2003-08-01

    In 1997, Wilmut et al. announced the birth of Dolly, the first ever clone of an adult animal. To date, adult sheep, goats, cattle, mice, pigs, cats and rabbits have been cloned using somatic cell nuclear transfer. The ultimate challenge of cloning procedures is to reprogram the somatic cell nucleus for development of the early embryo. The cell type of choice for reprogramming the somatic nucleus is an enucleated oocyte. Given that somatic cells are easily obtained from adult animals, cultured in the laboratory and then genetically modified, cloning procedures are ideal for introducing specific genetic modifications in farm animals. Genetic modification of farm animals provides a means of studying genes involved in a variety of biological systems and disease processes. Moreover, genetically modified farm animals have created a new form of 'pharming' whereby farm animals serve as bioreactors for production of pharmaceuticals or organ donors. A major limitation of cloning procedures is the extreme inefficiency for producing live offspring. Dolly was the only live offspring produced after 277 attempts. Similar inefficiencies for cloning adult animals of other species have been described by others. Many factors related to cloning procedures and culture environment contribute to the death of clones, both in the embryonic and fetal periods as well as during neonatal life. Extreme inefficiencies of this magnitude, along with the fact that death of the surrogate may occur, continue to raise great concerns with cloning humans. PMID:12846674

  8. The Associative Changes in Scutellum Nuclear Content and Morphology with Viability Loss of Naturally Aged and Accelerated Aging Wheat (Triticum aestivum) Seeds

    PubMed Central

    Ahmed, Zaheer; Yang, Hui; Fu, Yong-Bi

    2016-01-01

    Timely prediction of seed viability loss over long-term storage represents a challenge in management and conservation of ex situ plant genetic resources. However, little attention has been paid to study the process of seed deterioration and seed aging signals under storage. An attempt was made here to investigate morphological and molecular changes in the scutellum and aleurone sections of naturally or artificially aged wheat seeds using TUNEL assay and DAPI staining. Twelve wheat genotypes or samples exposed to natural ageing (NA) or accelerated ageing (AA) were assayed and these samples had germination rates ranging from 11 to 93%. The assayed samples showed substantial changes in scutellum, but not aleurone. The nuclei observed in the majority of the scutellum cells of the NA seed samples of lower germination rates were longer in size and less visible, while the scutellum cell morphology or arrangement remained unchanged. In contrast, longer AA treatments resulted in the loss of scutellum cell structure, collapse of cell layers, and disappearance of honey comb arrangements. These nuclei and structural changes were consistent with the DNA assessments of nuclear alternations for the selected wheat samples. Interestingly, the sample seed germination loss was found to be associated with the reductions in the scutellum nuclear content and with the increases in the scutellum nuclei length to width ratio. These findings are significant for understanding the process of wheat seed deterioration and are also useful for searching for sensitive seed aging signals for developing tools to monitor seed viability under storage. PMID:27729925

  9. Alabama Counseling Association Journal, 1998-1999.

    ERIC Educational Resources Information Center

    Magnuson, Sandy, Ed.; Norem, Ken, Ed.

    1999-01-01

    This document consists of the two issues of the "Alabama Counseling Association Journal" that make up volume 24. Articles in Issue 1 include: (1) "Learning Comes in Many Forms" (Holly Forester-Miller); (2) "Legislative, Legal, and Sociological Aspects of Alabama's Mental Health System" (David Gamble; Jamie S. Satcher); (3) "Peer Supervision: A…

  10. A hypothesis-driven association study of 28 nuclear-encoded mitochondrial genes with antipsychotic-induced weight gain in schizophrenia.

    PubMed

    Gonçalves, Vanessa F; Zai, Clement C; Tiwari, Arun K; Brandl, Eva J; Derkach, Andriy; Meltzer, Herbert Y; Lieberman, Jeffrey A; Müller, Daniel J; Sun, Lei; Kennedy, James L

    2014-05-01

    Mitochondria are the main source of energy for neurons and have a role in many vital neuronal functions. Mitochondrial dysfunction has been described in schizophrenia, and antipsychotics such as clozapine and olanzapine have been associated with differences in gene expression in mitochondria. We investigated the hypothesis that nuclear-encoded mitochondrial genes, particularly those involved in oxidative phosphorylation or involved in oxidative stress, mitochondrial biogenesis, inflammation, and apoptosis, would be associated with antipsychotic-induced weight gain (AIWG). In total, we selected 28 genes and analyzed 60 SNPs (50 are functional), in 283 schizophrenia subjects, treated with atypical medications for up to 14 weeks. Association between AIWG (as measured by the % of weight gain from baseline) and SNP genotypes were tested using linear regression with treatment duration, baseline body weight, and medication type as covariates. We observed a significant association between rs6435326 in the NDUFS1 gene and AIWG in the subset of European patients (N=150, Pcorrected=0.02). The haplotype carrying the risk alleles of rs6435326 and two other SNPs (rs1053517 and rs1801318) in NDUFS1 was also nominally associated with percentage of weight gain (T-C-G vs A-T-A, P=0.005). In addition, stepwise linear regression was performed to select important variables predictive of the outcome, and a gene-gene interaction analysis was carried out. We observed a significant interaction between the TT risk genotype of rs6435326 in NDUFS1 and AG genotype of rs3762883 in COX18 (Pcorrected=0.001). A permutation-based test of all 60 SNPs jointly showed significant association with weight gain (P=0.02). Finally, our replication study of rs6435326, rs1053517 and rs1801318 in NDUFS1 using samples from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) showed that rs1801318 was significantly associated with AIWG (N=200, Pcorrected=0.04), and the three SNPs were

  11. Nuclear proteins TREF1 and TREF2 bind to the transcriptional control element of the transferrin receptor gene and appear to be associated as a heterodimer.

    PubMed Central

    Roberts, M R; Miskimins, W K; Ruddle, F H

    1989-01-01

    Two novel proteins that bind specifically to the transferrin receptor (TR) promoter, have been isolated from HeLa cell nuclear extract using a combination of ion exchange and oligonucleotide-affinity chromatography. TREF1 and TREF2, which have apparent molecular weights of 82 and 62 kDa, respectively, appear to be associated as a heterocomplex (TREF), and both proteins are able to contact target DNA directly. TREF interacts specifically with a region of the TR promoter which contains the TR transcriptional control element. This region is similar in sequence to the cAMP-responsive and phorbol ester-responsive elements found in several viral and cellular genes. Binding of TREF to the TR promoter results in modification of DNA topology over multiple helical turns, including a sequence revealed by a helical periodicity map as having an unusual structure. Images PMID:2519614

  12. MCF-7 cells expressing nuclear associated lysyl oxidase-like 2 (LOXL2) exhibit an epithelial-to-mesenchymal transition (EMT) phenotype and are highly invasive in vitro.

    PubMed

    Moon, Hee-Jung; Finney, Joel; Xu, Li; Moore, David; Welch, Danny R; Mure, Minae

    2013-10-18

    LOXL2 is a copper- and lysine tyrosylquinone-dependent amine oxidase that has been proposed to function both extracellularly and intracellularly to activate oncogenic signaling pathways leading to EMT and invasion of breast cancer cells. In this study, we selected MCF-7 cells that stably express forms of recombinant LOXL2 differing in their subcellular localizations and catalytic competencies. This enabled us to dissect the molecular functions of intracellular and extracellular LOXL2s and examine their contributions to breast cancer metastasis/invasion. We discovered that secreted LOXL2 (~100-kDa) is N-glycosylated at Asn-455 and Asn-644, whereas intracellular LOXL2 (~75-kDa) is nonglycosylated and N-terminally processed, and is primarily associated with the nucleus. Both forms of LOXL2 can oxidize lysine in solution. However, we found that expression of intracellular LOXL2 is more strongly associated with EMT and invasiveness than secreted LOXL2 in vitro. The results indicate that nuclear associated LOXL2 contributes to the stabilization of Snail1 transcription factor at the protein level to induce EMT and promote invasion in vitro, through repression of E-cadherin, occludin, and estrogen receptor-α, and up-regulation of vimentin, fibronectin, and MT1-MMP.

  13. The nuclear matrix protein p255 is a highly phosphorylated form of RNA polymerase II largest subunit which associates with spliceosomes.

    PubMed Central

    Vincent, M; Lauriault, P; Dubois, M F; Lavoie, S; Bensaude, O; Chabot, B

    1996-01-01

    The monoclonal antibody CC-3 recognizes a phosphodependent epitope on a 255 kDa nuclear matrix protein (p255) recently shown to associate with splicing complexes as part of the [U4/U6.U5] tri-snRNP particle [Chabot et al. (1995) Nucleic Acids Res. 23, 3206-3213]. In mouse and Drosophila cultured cells the electrophoretic mobility of p255, faster in the latter species, was identical to that of the hyperphosphorylated form of RNA polymerase II largest subunit (IIo). The CC-3 immunoreactivity of p255 was abolished by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, which is known to cause the dephosphorylation of the C-terminal domain of subunit IIo by inhibiting the TFIIH-associated kinase. The identity of p255 was confirmed by showing that CC-3-immunoprecipitated p255 was recognized by POL3/3 and 8WG16, two antibodies specific to RNA polymerase II largest subunit. Lastly, the recovery of RNA polymerase II largest subunit from HeLa splicing mixtures was compromised by EDTA, which prevents the interaction of p255 with splicing complexes and inhibits splicing. Our results indicate that p255 represents a highly phosphorylated form of RNA polymerase II largest subunit physically associated with spliceosomes and possibly involved in coupling transcription to RNA processing. PMID:8972849

  14. PML nuclear bodies and SATB1 are associated with HLA class I expression in EBV+ Hodgkin lymphoma.

    PubMed

    Liu, Yuxuan; van den Berg, Anke; Veenstra, Rianne; Rutgers, Bea; Nolte, Ilja; van Imhoff, Gustaaf; Visser, Lydia; Diepstra, Arjan

    2013-01-01

    Tumor cells of classical Hodgkin lymphoma (cHL) are characterized by a general loss of B cell phenotype, whereas antigen presenting properties are commonly retained. HLA class I is expressed in most EBV+ cHL cases, with an even enhanced expression in a proportion of the cases. Promyelocytic leukemia protein (PML) and special AT-rich region binding protein 1 (SATB1) are two global chromatin organizing proteins that have been shown to regulate HLA class I expression in Jurkat cells. We analyzed HLA class I, number of PML nuclear bodies (NBs) and SATB1 expression in tumor cells of 54 EBV+ cHL cases and used 27 EBV- cHL cases as controls. There was a significant difference in presence of HLA class I staining between EBV+ and EBV- cases (p<0.0001). We observed normal HLA class I expression in 35% of the EBV+ and in 19% of the EBV- cases. A stronger than normal HLA class I expression was observed in approximately 40% of EBV+ cHL and not in EBV- cHL cases. 36 EBV+ cHL cases contained less than 10 PML-NBs per tumor cell, whereas 16 cases contained more than 10 PML-NBs. The number of PML-NBs was positively correlated to the level of HLA class I expression (p<0.01). The percentage of SATB1 positive cells varied between 0% to 100% in tumor cells and was inversely correlated with the level of HLA class I expression, but only between normal and strong expression (p<0.05). Multivariable analysis indicated that the number of PML-NBs and the percentage of SATB1+ tumor cells are independent factors affecting HLA class I expression in EBV+ cHL. In conclusion, both PML and SATB1 are correlated to HLA class I expression levels in EBV+ cHL.

  15. Evaluation of radiation doses and associated risk from the Fukushima nuclear accident to marine biota and human consumers of seafood.

    PubMed

    Fisher, Nicholas S; Beaugelin-Seiller, Karine; Hinton, Thomas G; Baumann, Zofia; Madigan, Daniel J; Garnier-Laplace, Jacqueline

    2013-06-25

    Radioactive isotopes originating from the damaged Fukushima nuclear reactor in Japan following the earthquake and tsunami in March 2011 were found in resident marine animals and in migratory Pacific bluefin tuna (PBFT). Publication of this information resulted in a worldwide response that caused public anxiety and concern, although PBFT captured off California in August 2011 contained activity concentrations below those from naturally occurring radionuclides. To link the radioactivity to possible health impairments, we calculated doses, attributable to the Fukushima-derived and the naturally occurring radionuclides, to both the marine biota and human fish consumers. We showed that doses in all cases were dominated by the naturally occurring alpha-emitter (210)Po and that Fukushima-derived doses were three to four orders of magnitude below (210)Po-derived doses. Doses to marine biota were about two orders of magnitude below the lowest benchmark protection level proposed for ecosystems (10 µGy⋅h(-1)). The additional dose from Fukushima radionuclides to humans consuming tainted PBFT in the United States was calculated to be 0.9 and 4.7 µSv for average consumers and subsistence fishermen, respectively. Such doses are comparable to, or less than, the dose all humans routinely obtain from naturally occurring radionuclides in many food items, medical treatments, air travel, or other background sources. Although uncertainties remain regarding the assessment of cancer risk at low doses of ionizing radiation to humans, the dose received from PBFT consumption by subsistence fishermen can be estimated to result in two additional fatal cancer cases per 10,000,000 similarly exposed people.

  16. Evaluation of radiation doses and associated risk from the Fukushima nuclear accident to marine biota and human consumers of seafood

    PubMed Central

    Fisher, Nicholas S.; Beaugelin-Seiller, Karine; Hinton, Thomas G.; Baumann, Zofia; Madigan, Daniel J.; Garnier-Laplace, Jacqueline

    2013-01-01

    Radioactive isotopes originating from the damaged Fukushima nuclear reactor in Japan following the earthquake and tsunami in March 2011 were found in resident marine animals and in migratory Pacific bluefin tuna (PBFT). Publication of this information resulted in a worldwide response that caused public anxiety and concern, although PBFT captured off California in August 2011 contained activity concentrations below those from naturally occurring radionuclides. To link the radioactivity to possible health impairments, we calculated doses, attributable to the Fukushima-derived and the naturally occurring radionuclides, to both the marine biota and human fish consumers. We showed that doses in all cases were dominated by the naturally occurring alpha-emitter 210Po and that Fukushima-derived doses were three to four orders of magnitude below 210Po-derived doses. Doses to marine biota were about two orders of magnitude below the lowest benchmark protection level proposed for ecosystems (10 µGy⋅h−1). The additional dose from Fukushima radionuclides to humans consuming tainted PBFT in the United States was calculated to be 0.9 and 4.7 µSv for average consumers and subsistence fishermen, respectively. Such doses are comparable to, or less than, the dose all humans routinely obtain from naturally occurring radionuclides in many food items, medical treatments, air travel, or other background sources. Although uncertainties remain regarding the assessment of cancer risk at low doses of ionizing radiation to humans, the dose received from PBFT consumption by subsistence fishermen can be estimated to result in two additional fatal cancer cases per 10,000,000 similarly exposed people. PMID:23733934

  17. Evaluation of radiation doses and associated risk from the Fukushima nuclear accident to marine biota and human consumers of seafood.

    PubMed

    Fisher, Nicholas S; Beaugelin-Seiller, Karine; Hinton, Thomas G; Baumann, Zofia; Madigan, Daniel J; Garnier-Laplace, Jacqueline

    2013-06-25

    Radioactive isotopes originating from the damaged Fukushima nuclear reactor in Japan following the earthquake and tsunami in March 2011 were found in resident marine animals and in migratory Pacific bluefin tuna (PBFT). Publication of this information resulted in a worldwide response that caused public anxiety and concern, although PBFT captured off California in August 2011 contained activity concentrations below those from naturally occurring radionuclides. To link the radioactivity to possible health impairments, we calculated doses, attributable to the Fukushima-derived and the naturally occurring radionuclides, to both the marine biota and human fish consumers. We showed that doses in all cases were dominated by the naturally occurring alpha-emitter (210)Po and that Fukushima-derived doses were three to four orders of magnitude below (210)Po-derived doses. Doses to marine biota were about two orders of magnitude below the lowest benchmark protection level proposed for ecosystems (10 µGy⋅h(-1)). The additional dose from Fukushima radionuclides to humans consuming tainted PBFT in the United States was calculated to be 0.9 and 4.7 µSv for average consumers and subsistence fishermen, respectively. Such doses are comparable to, or less than, the dose all humans routinely obtain from naturally occurring radionuclides in many food items, medical treatments, air travel, or other background sources. Although uncertainties remain regarding the assessment of cancer risk at low doses of ionizing radiation to humans, the dose received from PBFT consumption by subsistence fishermen can be estimated to result in two additional fatal cancer cases per 10,000,000 similarly exposed people. PMID:23733934

  18. Flower-enhanced expression of a nuclear-encoded mitochondrial respiratory protein is associated with changes in mitochondrion number.

    PubMed Central

    Huang, J; Struck, F; Matzinger, D F; Levings, C S

    1994-01-01

    The mitochondrial Rieske iron-sulfur protein is an obligatory component of the respiratory electron transport chain that is encoded by a single-copy gene in mammals and fungi. In contrast, this protein is encoded by a small gene family in dicotyledonous tobacco and monocotyledonous maize. We cloned four cDNAs from tobacco that encode the mitochondrial Rieske iron-sulfur protein. These clones, along with a previously isolated cDNA, represent five independent members of the gene family that can be divided into three subfamilies. All of these genes were derived from the two progenitor species and were expressed in amphidiploid tobacco. The proteins encoded by these five genes are probably functional because they all contain the universally conserved hexyl peptides necessary for the 2Fe-2S cluster formation. The expression of the Rieske protein gene family is differentially regulated; a 6- to 11-fold higher level of steady state transcripts was found in flowers than in leaves, stems, and roots. Members of at least two subfamilies were preferentially expressed in flowers, indicating that they share a common cis-regulatory element(s), which can respond to a flower-specific signal(s). Although approximately 10 times more transcripts occurred in flowers than in leaves, flower and leaf mitochondria contained a similar amount of the Rieske protein. Flowers, however, contained seven times more Rieske proteins than leaves. These results indicated an increase in mitochondrion number in flowers. High-energy demands during anther development might bring about an increase in mitochondrion numbers in flowers and the flower-enhanced expression of the Rieske protein gene family. Our results suggested that nuclear genes encoding mitochondrial respiratory proteins could sense and respond to changes in energy metabolism and/or changes in mitochondrion numbers. PMID:8180500

  19. Osteoprotegerin (OPG), but not Receptor Activator for Nuclear Factor Kappa B Ligand (RANKL), is Associated with Subclinical Coronary Atherosclerosis in HIV-infected Men

    PubMed Central

    Ketlogetswe, Kerunne S; McKibben, Rebeccah; Jacobson, Lisa P; Li, Xuihong; Dobs, Adrian S; Budoff, Matthew; Witt, Mallory D; Palella, Frank J; Kingsley, Lawrence; Margolick, Joseph B.; Post, Wendy S; Brown, Todd T.

    2015-01-01

    Context Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease pathogenesis in the general population. Objective To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis. Design Cross-sectional study nested within the Multicenter AIDS Cohort Study Setting Four US academic medical centers Participants There were 578 HIV-infected and 344 HIV-uninfected men. Main Outcome Measures Coronary artery calcium (CAC) was measured by non-contrast cardiac computed tomography (CT), and coronary stenosis and plaque characteristics (composition, presence and extent) were measured by coronary CT angiography. All statistical models were adjusted for traditional cardiovascular risk factors. Results OPG concentrations were higher and RANKL concentrations were lower among HIV-infected men compared to –uninfected men (p<0.0001 each). Among the HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis > 50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with extent of both CAC and calcified plaque, but not their presence. RANKL concentrations were not associated with plaque presence or extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque. Conclusions OPG and RANKL are dysregulated in HIV-infected men and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV-status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men. PMID:26090754

  20. Response to the Point of View of Gregory B. Pauly, David M. Hillis, and David C. Cannatella, by the Anuran Subcommittee of the SSAR/HL/ASIH Scientific and Standard English Names List

    USGS Publications Warehouse

    Frost, Darrel R.; McDiarmid, Roy W.; Mendelson, Joseph R.

    2009-01-01

    The Point of View by Gregory Pauly, David Hillis, and David Cannatella misrepresents the motives and activities of the anuran subcommittee of the Scientific and Standard English Names Committee, contains a number of misleading statements, omits evidence and references to critical literature that have already rejected or superseded their positions, and cloaks the limitations of their nomenclatural approach in ambiguous language. Their Point of View is not about promoting transparency in the process of constructing the English Names list, assuring that its taxonomy is adequately reviewed, or promoting nomenclatural stability in any global sense. Rather, their Point of View focuses in large part on a single publication, The Amphibian Tree of Life, which is formally unrelated to the Standard English Names List, and promotes an approach to nomenclature mistakenly asserted by them to be compatible with both the International Code of Zoological Nomenclature and one of its competitors, the PhyloCode.

  1. Downregulation of Nuclear Factor Erythroid 2-Related Factor and Associated Antioxidant Genes Contributes to Redox-Sensitive Vascular Dysfunction in Hypertension.

    PubMed

    Lopes, Rhéure A; Neves, Karla B; Tostes, Rita C; Montezano, Augusto C; Touyz, Rhian M

    2015-12-01

    Oxidative stress is implicated in vascular dysfunction in hypertension. Although mechanisms regulating vascular pro-oxidants are emerging, there is a paucity of information on antioxidant systems, particularly nuclear factor erythroid 2-related factor (Nrf2), a master regulator of antioxidants enzymes. We evaluated the vascular regulatory role of Nrf2 in hypertension and examined molecular mechanisms, whereby Nrf2 influences redox signaling in small arteries and vascular smooth muscle cells from Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Cells were stimulated with angiotensin II in the absence/presence of Nrf2 activators (bardoxolone/L-sulforaphane). Increased vascular reactive oxygen species production (chemiluminescence and amplex red) was associated with reduced Nrf2 activity in arteries (18%) and vascular smooth muscle cells (48%) in SHRSP (P<0.05 versus WKY). Expression of antioxidant enzymes, including superoxide dismutase-1 (64%), catalase (60%), peroxiredoxin 1 (75%), and glutathione peroxidase (54%), was reduced in SHRSP. L-sulforaphane reversed these effects. Angiotensin II increased nuclear accumulation of Nrf2 in vascular smooth muscle cells from WKY (197% versus vehicle), with blunted effects in SHRSP (44% versus vehicle). These responses were associated with increased antioxidant expression (superoxide dismutase-1, 32%; catalase, 42%; thioredoxin, 71%; peroxiredoxin, 1%-90%; quinone oxidoreductase, 84%; P<0.05 versus vehicle) and increased activity of superoxide dismutase-1, catalase, and thioredoxin in WKY but not in SHRSP, which exhibited increased Bach1 expression. Nrf2 activators blocked angiotensin II-induced reactive oxygen species generation. Vascular function demonstrated increased contractility (Emax WKY 113.4±5.6 versus SHRSP 159.0±8.3) and decreased endothelial-dependent relaxation (Emax WKY 88.6±3.1 versus SHRSP 74.6±3.2, P<0.05) in SHRSP, effects corrected by L-sulforaphane. Our findings suggest that

  2. Early embryonic death-associated changes in genome-wide gene expression profiles in the fetal placenta of the cow carrying somatic nuclear-derived cloned embryo.

    PubMed

    Oishi, Masahito; Gohma, Hiroshi; Hashizume, Kazuyoshi; Taniguchi, Yukio; Yasue, Hiroshi; Takahashi, Seiya; Yamada, Takahisa; Sasaki, Yoshiyuki

    2006-04-01

    Successful somatic nuclear transfer-derived cloning has been reported in cattle; however, the cloned embryo is highly susceptible to death around day 60 of gestation leading to early embryonic loss. The early embryonic death is postulated to possibly arise in part from an atypical placentation. We have performed cDNA macroarray analysis using 3,353 of the previously cataloged 4,165 genes, in order to characterize the early embryonic death-associated changes in genome-wide gene expression profiles in the fetal placenta of the cow carrying somatic nuclear transfer-derived cloned embryo. A more marked difference in the expression profiles was observed between the fetal placentas of the cows with the cloned immotile embryo (CD) and with the cloned motile embryo (CL) or artificial insemination-derived motile embryo (AI), as compared to between the CL and AI placentas, suggesting an aberration of the expression profile in the CD placenta among the three placentas. Further, 291 and 77 genes showed more than twofold elevation and less than 50% reduction, respectively, in either or both of two CD (CD1 and CD2) placentas in comparison with the CL placenta, but no differential expression between the CL and AI placentas. The expression patterns of six genes in the AI, CL, and CD placentas were confirmed in an experiment with an additional sample for each of the three placentas. Among the placental genes showing the early embryonic death-associated changes of expression in the cow with the cloned embryo, IGF2 (elevated gene), and HBA1, HBA2, SPTB, and SPTBN1 genes (reduced gene) are intriguing in that the changes of expression in these genes were observed in an additional sample of CD placenta as well as the CD1 and CD2 placentas, and in that overexpression (for IGF2) and dysfunction or deficiency (for HBA1, HBA2, SPTB, and SPTBN1) result in embryonic lethality.

  3. Plasticity, stability, and yield: the origins of Anthony David Bradshaw's model of adaptive phenotypic plasticity.

    PubMed

    Peirson, B R Erick

    2015-04-01

    Plant ecologist Anthony David Bradshaw's account of the evolution of adaptive phenotypic plasticity remains central to contemporary research aimed at understanding how organisms persist in heterogeneous environments. Bradshaw suggested that changes in particular traits in response to specific environmental factors could be under direct genetic control, and that natural selection could therefore act directly to shape those responses: plasticity was not "noise" obscuring a genetic signal, but could be specific and refined just as any other adaptive phenotypic trait. In this paper, I document the contexts and development of Bradshaw's investigation of phenotypic plasticity in plants, including a series of unreported experiments in the late 1950s and early 1960s. Contrary to the mythology that later emerged around Bradshaw's ideas, Bradshaw was engaged in a serious and sustained empirical research program concerning plasticity in the 1950s and 1960s that went far beyond a single review paper. Moreover, that work was not isolated, but was surrounded by an already rich theoretical discourse and a substantial body of empirical research concerning the evolution of developmental plasticity and stability. Bradshaw recast the problem of how to understand (and control) plasticity and stability within an epistemic framework focused on genetic differences and natural selection. PMID:25641217

  4. David J. Triggle: Medicinal chemistry, to pharmacology, calcium channels, and beyond.

    PubMed

    Walker, Michael J A

    2015-11-15

    David Triggle's scientific career began as a chemist, went through medicinal chemistry into pharmacology, and finally on to somewhat more philosophical interests in later years. It was a career marked by many contributions to all of those aspects of science. Chief amongst his many contributions, in addition to those in medicinal chemistry, was his work on the drugs known as calcium ion channel blockers or (calcium antagonists). In the calcium ion channel field he was a particularly instrumental figure in sorting out the mechanisms, actions and roles of the class of calcium channel blockers, known chemical and pharmacologically as the dihydropyridines (DHPs) in particular, as well as other calcium blockers of diverse structures. During the course of a long career, and extensive journeys into medicinal chemistry and pharmacology, he published voluminously in terms of papers, reviews, conference proceedings and books. Notably, many of his papers often had limited authorship where, as senior author it reflected his deep involvement in all aspects of the reported work. His work always helped clarify the field while his incisive reviews, together with his role in coordinating and running scientific meetings, were a great help in clarifying and organizing various fields of study. He has had a long and illustrious career, and is wellknown in the world of biomedical science; his contributions are appreciated, and well recognized everywhere. The following article attempts to chart a path through his work and contributions to medicinal chemistry, pharmacology, science, academia and students.

  5. Integration of approaches in David Wake's model-taxon research platform for evolutionary morphology.

    PubMed

    Griesemer, James

    2013-12-01

    What gets integrated in integrative scientific practices has been a topic of much discussion. Traditional views focus on theories and explanations, with ideas of reduction and unification dominating the conversation. More recent ideas focus on disciplines, fields, or specialties; models, mechanisms, or methods; phenomena, problems. How integration works looks different on each of these views since the objects of integration are ontologically and epistemically various: statements, boundary conditions, practices, protocols, methods, variables, parameters, domains, laboratories, and questions all have their own structures, functions and logics. I focus on one particular kind of scientific practice, integration of "approaches" in the context of a research system operating on a special kind of "platform." Rather than trace a network of interactions among people, practices, and theoretical entities to be integrated, in this essay I focus on the work of a single investigator, David Wake. I describe Wake's practice of integrative evolutionary biology and how his integration of approaches among biological specialties worked in tandem with his development of the salamanders as a model taxon, which he used as a platform to solve, re-work and update problems that would not have been solved so well by non-integrative approaches. The larger goal of the project to which this paper contributes is a counter-narrative to the story of 20th century life sciences as the rise and march of the model organisms and decline of natural history.

  6. DEVELOPMENT OF PLASTICITY MODEL USING NON ASSOCIATED FLOW RULE FOR HCP MATERIALS INCLUDING ZIRCONIUM FOR NUCLEAR APPLICATIONS

    SciTech Connect

    Michael V. Glazoff; Jeong-Whan Yoon

    2013-08-01

    In this report (prepared in collaboration with Prof. Jeong Whan Yoon, Deakin University, Melbourne, Australia) a research effort was made to develop a non associated flow rule for zirconium. Since Zr is a hexagonally close packed (hcp) material, it is impossible to describe its plastic response under arbitrary loading conditions with any associated flow rule (e.g. von Mises). As a result of strong tension compression asymmetry of the yield stress and anisotropy, zirconium displays plastic behavior that requires a more sophisticated approach. Consequently, a new general asymmetric yield function has been developed which accommodates mathematically the four directional anisotropies along 0 degrees, 45 degrees, 90 degrees, and biaxial, under tension and compression. Stress anisotropy has been completely decoupled from the r value by using non associated flow plasticity, where yield function and plastic potential have been treated separately to take care of stress and r value directionalities, respectively. This theoretical development has been verified using Zr alloys at room temperature as an example as these materials have very strong SD (Strength Differential) effect. The proposed yield function reasonably well models the evolution of yield surfaces for a zirconium clock rolled plate during in plane and through thickness compression. It has been found that this function can predict both tension and compression asymmetry mathematically without any numerical tolerance and shows the significant improvement compared to any reported functions. Finally, in the end of the report, a program of further research is outlined aimed at constructing tensorial relationships for the temperature and fluence dependent creep surfaces for Zr, Zircaloy 2, and Zircaloy 4.

  7. David Blackwell’s Forty Years in the Idaho Desert, The Foundation for 21st Century Geothermal Research

    SciTech Connect

    McLing, Travis; McCurry, Mike; Cannon, Cody; Neupane, Ghanashyam; Wood, Thomas; Podgorney, Robert; Welhan, John; Mines, Greg; Mattson, Earl; Wood, Rachel; Palmer, Carl

    2015-04-01

    Dr. David Blackwell has had a profound influence on geo-thermal exploration and R&D in Idaho. Forty years have elapsed since the first Southern Methodist University (SMU) temperature logging truck rolled onto the high desert in Southern Idaho, yet even after so much time has elapsed, most recent and ongoing geothermal R&D can trace its roots to the foundational temperature studies led by Dr. Blackwell. We believe that the best way to honor any scientist is to see their work carried forward by others. As this paper demonstrates, it has been an easy task to find a host of Idaho researchers and students eager to contribute to this tribute paper. We organize this paper by ongoing or recent projects that continue to benefit left to Idaho by Dr. David Blackwell.

  8. Human THAP7 is a chromatin-associated, histone tail-binding protein that represses transcription via recruitment of HDAC3 and nuclear hormone receptor corepressor.

    PubMed

    Macfarlan, Todd; Kutney, Sara; Altman, Brian; Montross, Rebecca; Yu, Jiujiu; Chakravarti, Debabrata

    2005-02-25

    The identities of signal transducer proteins that integrate histone hypoacetylation and transcriptional repression are largely unknown. Here we demonstrate that THAP7, an uncharacterized member of the recently identified THAP (Thanatos-associated protein) family of proteins, is ubiquitously expressed, associates with chromatin, and represses transcription. THAP7 binds preferentially to hypoacetylated (un-, mono-, and diacetylated) histone H4 tails in vitro via its C-terminal 77 amino acids. Deletion of this domain, or treatment of cells with the histone deacetylase inhibitor TSA, which leads to histone hyperacetylation, partially disrupts THAP7/chromatin association in living cells. THAP7 coimmunoprecipitates with histone deacetylase 3 (HDAC3) and the nuclear hormone receptor corepressor (NCoR) and represses transcription as a Gal4 fusion protein. Chromatin immunoprecipitation assays demonstrate that these corepressors are recruited to promoters in a THAP7 dependent manner and promote histone H3 hypoacetylation. The conserved THAP domain is a key determinant for full HDAC3 association in vitro, and both the THAP domain and the histone interaction domain are important for the repressive properties of THAP7. Full repression mediated by THAP7 is also dependent on NCoR expression. We hypothesize that THAP7 is a dual function repressor protein that actively targets deacetylation of histone H3 necessary to establish transcriptional repression and functions as a signal transducer of the repressive mark of hypoacetylated histone H4. This is the first demonstration of the transcriptional regulatory properties of a human THAP domain protein, and a critical identification of a potential transducer of the repressive signal of hypoacetylated histone H4 in higher eukaryotes. PMID:15561719

  9. Affirming Psychological Science--For Students, Teachers, and the Larger World: An Interview With David G. Myers

    ERIC Educational Resources Information Center

    Miller, Jr., Harold L.

    2005-01-01

    David G. Myers received a BA in chemistry, magna cum laude from Whitworth College and an MA and PhD in psychology from the University of Iowa. Since 1982 he has been the John Dirk Werkman Professor of Psychology at Hope College. He is best known for his authorship of Psychology (2004), now in its 7th edition, and Social Psychology (2005a), now in…

  10. STS-57 MS and PLC G. David Low examines CGBA pack in OV-105's SPACEHAB module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-57 Mission Specialist (MS) and Payload Commander (PLC) G. David Low examines Commercial Generic Bioprocessing Apparatus (CGBA) group activation pack (GAP) incubator while in front of the SPACEHAB-01 (Commercial Middeck Augmentation Module (CMAM)) aft lockers. Low has temporarily removed the GAP from its locker location. Crewmembers are conducting a variety of experiments inside SPACEHAB-01 module which is positioned in the payload bay (PLB) of the Earth-orbiting Endeavour, Orbiter Vehicle (OV) 105.

  11. STS-32 MS G. David Low dons LES CCA in KSC LC Pad 39A white room

    NASA Technical Reports Server (NTRS)

    1990-01-01

    STS-32 Mission Specialist (MS) G. David Low, wearing launch and entry suit (LES), fastens strap on LES communications carrier assembly (CCA) cap in the white room on the orbiter access arm at Kennedy Space Center (KSC) Launch Complex (LC) Pad 39A. Technicians oversee the suiting operations. MS Marsha S. Ivins sits next to Low. When fully equipped, Low and Ivins will enter Columbia, Orbiter Vehicle (OV) 102, side hatch which appears in the background.

  12. Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15 years.

    PubMed

    Selmi, Carlo; Ceribelli, Angela; Generali, Elena; Scirè, Carlo A; Alborghetti, Fausto; Colloredo, Guido; Porrati, Luisa; Achenza, Maria I S; De Santis, Maria; Cavaciocchi, Francesca; Massarotti, Marco; Isailovic, Natasa; Paleari, Valentina; Invernizzi, Pietro; Matthias, Torsten; Zucchi, Alberto; Meroni, Pier Luigi

    2016-02-01

    The prevalence of ANA and anti-ENA in the general population is not well established, especially their clinical significance in healthy subjects. We herein determined the prevalence and predictive value of serum ANA and anti-ENA for connective tissue diseases (CTD), cancer, and mortality. We took advantage of a randomly selected sample of the 1998 general population (Isola I) consisting of 2828 subjects (53% women, age 43±13 years) from a well-defined Northern Italian area. Serum ANA and anti-ENA were tested on the 2690 samples available in 2012 (Isola II, 50% women, age 58±13 years). Administrative databases were searched for CTD, cancer diagnosis, and death cases occurring between enrollment and December 31, 2013. The hazard ratio (HR) was calculated for incident cases. Serum ANA is positive in 18.1% for any titer and 6.1% for titers ≥1:160, 23% in subjects over 50 years and 13.1% and 6.1% for any titer and titers ≥1:160, respectively, in women. The HR for CTD development was significantly high for all ANA titers, with the highest for ANA ≥1:160 (HR 14.19, 95% CI 3.07-65.68). ANA positivity was not associated with cancer (HR 1.03; 95% CI 0.75-1.43), or with mortality (HR adjusted for age and sex 1.40; 95% CI 0.94-2.09). Serum anti-ENA is positive in a minority of subjects with highest figures for anti-nucleosome (1.9%), -histone (1.6%) and -PM/Scl (1.5%). In conclusion, serum ANA prevalence in the general population is highest in senior subjects and in women, while the female predominance is significantly lower compared to overt CTD. Serum ANA is associated with an increased probability of CTD development over time, but does not influence survival or cancer risk.

  13. Evaluation of MLC leaf positioning accuracy for static and dynamic IMRT treatments using DAVID in vivo dosimetric system.

    PubMed

    Karagoz, Gulay; Zorlu, Faruk; Yeginer, Mete; Yildiz, Demet; Ozyigit, Gokhan

    2016-01-01

    Accuracy and precision of leaf positioning in multileaf collimators (MLCs) are significant factors for the accuracy of IMRT treatments. This study aimed to inves-tigate the accuracy and repeatability of the MLC leaf positioning via the DAVID invivo dosimetric system for dynamic and static MLC systems. The DAVID system was designed as multiwire transmission ionization chamber which is placed in accessory holder of linear accelerators. Each wire of DAVID system corresponds to a MLC leaf-pair to verify the leaf positioning accuracy during IMRT treatment and QA. In this study, verifications of IMRT plans of five head and neck (H&N) and five prostate patients treated in a Varian DHX linear accelerator with 80-leaf MLC were performed using DAVID system. Before DAVID-based dosimetry, Electronics Portal Imaging Device (EPID) and PTW 2D ARRAY dosimetry system were used for 2D verification of each plan. The measurements taken by DAVID system in the first day of the treatments were used as reference for the following measurements taken over the next four weeks. The deviations in leaf positioning were evaluated by "Total Deviation (TD)" parameter calculated by DAVID software. The delivered IMRT plans were originally prepared using dynamic MLC method. The same plans were subsequently calculated based on static MLC method with three different intensity levels of five (IL5), 10 (IL10) and 20 (IL20) in order to compare the performances of MLC leaf positioning repeatability for dynamic and static IMRT plans. The leaf positioning accuracy is also evaluated by analyzing DynaLog files based on error histograms and root mean square (RMS) errors of leaf pairs' positions. Moreover, a correlation analysis between simultaneously taken DAVID and EPID measurements and DynaLog file recordings was subsequently performed. In the analysis of DAVID outputs, the overall deviations of dynamic MLC-based IMRT calculated from the deviations of the four weeks were found as 0.55% ± 0.57% and 1.48% ± 0

  14. Evaluation of MLC leaf positioning accuracy for static and dynamic IMRT treatments using DAVID in vivo dosimetric system.

    PubMed

    Karagoz, Gulay; Zorlu, Faruk; Yeginer, Mete; Yildiz, Demet; Ozyigit, Gokhan

    2016-03-08

    Accuracy and precision of leaf positioning in multileaf collimators (MLCs) are significant factors for the accuracy of IMRT treatments. This study aimed to inves-tigate the accuracy and repeatability of the MLC leaf positioning via the DAVID invivo dosimetric system for dynamic and static MLC systems. The DAVID system was designed as multiwire transmission ionization chamber which is placed in accessory holder of linear accelerators. Each wire of DAVID system corresponds to a MLC leaf-pair to verify the leaf positioning accuracy during IMRT treatment and QA. In this study, verifications of IMRT plans of five head and neck (H&N) and five prostate patients treated in a Varian DHX linear accelerator with 80-leaf MLC were performed using DAVID system. Before DAVID-based dosimetry, Electronics Portal Imaging Device (EPID) and PTW 2D ARRAY dosimetry system were used for 2D verification of each plan. The measurements taken by DAVID system in the first day of the treatments were used as reference for the following measurements taken over the next four weeks. The deviations in leaf positioning were evaluated by "Total Deviation (TD)" parameter calculated by DAVID software. The delivered IMRT plans were originally prepared using dynamic MLC method. The same plans were subsequently calculated based on static MLC method with three different intensity levels of five (IL5), 10 (IL10) and 20 (IL20) in order to compare the performances of MLC leaf positioning repeatability for dynamic and static IMRT plans. The leaf positioning accuracy is also evaluated by analyzing DynaLog files based on error histograms and root mean square (RMS) errors of leaf pairs' positions. Moreover, a correlation analysis between simultaneously taken DAVID and EPID measurements and DynaLog file recordings was subsequently performed. In the analysis of DAVID outputs, the overall deviations of dynamic MLC-based IMRT calculated from the deviations of the four weeks were found as 0.55% ± 0.57% and 1.48% ± 0

  15. Nuclear accumulation of Yes-Associated Protein (YAP) maintains the survival of doxorubicin-induced senescent cells by promoting survivin expression.

    PubMed

    Ma, Kai; Xu, Qing; Wang, Shuren; Zhang, Weina; Liu, Mei; Liang, Shufang; Zhu, Hongxia; Xu, Ningzhi

    2016-05-28

    Although chemotherapeutic drugs can induce senescence to prohibit further division of tumor cells, senescence could also promote tumorigenesis mainly through a senescence-associated secretory phenotype. Therefore, senescent tumor cells should be eliminated immediately to prevent drug resistance and recurrence. Here, we used a doxorubicin-induced senescence model to explore the mechanism underlying the survival of therapy-induced senescent cells. After low-dose doxorubicin treatment, tumor cells turned on a senescence program and became large and flattened, increasing their contact area with the extracellular matrix (ECM). Furthermore, Yes-associated protein (YAP) accumulated in the nucleus and YAP activity was increased in doxorubicin-induced senescent cells. Knockdown of YAP increased the sensitivity of cells to low-dose doxorubicin treatment, causing apoptosis rather than senescence. Moreover, the anti-apoptotic gene survivin, a YAP target gene, was overexpressed in senescent cells. Inhibition of survivin could lead to selective elimination of senescent cells through apoptosis. Our study indicates that nuclear accumulation of YAP could promote the survival of senescent cells by increasing survivin expression. Therefore, targeting YAP or survivin might be a new strategy for clearing senescent cancer cells during drug treatment.

  16. Cooperativity among Rev-Associated Nuclear Export Signals Regulates HIV-1 Gene Expression and Is a Determinant of Virus Species Tropism

    PubMed Central

    Aligeti, Mounavya; Behrens, Ryan T.; Pocock, Ginger M.; Schindelin, Johannes; Dietz, Christian; Eliceiri, Kevin W.; Swanson, Chad M.; Malim, Michael H.; Ahlquist, Paul

    2014-01-01

    ABSTRACT Murine cells exhibit a profound block to HIV-1 virion production that was recently mapped to a species-specific structural attribute of the murine version of the chromosomal region maintenance 1 (mCRM1) nuclear export receptor and rescued by the expression of human CRM1 (hCRM1). In human cells, the HIV-1 Rev protein recruits hCRM1 to intron-containing viral mRNAs encoding the Rev response element (RRE), thereby facilitating viral late gene expression. Here we exploited murine 3T3 fibroblasts as a gain-of-function system to study hCRM1's species-specific role in regulating Rev's effector functions. We show that Rev is rapidly exported from the nucleus by mCRM1 despite only weak contributions to HIV-1's posttranscriptional stages. Indeed, Rev preferentially accumulates in the cytoplasm of murine 3T3 cells with or without hCRM1 expression, in contrast to human HeLa cells, where Rev exhibits striking en masse transitions between the nuclear and cytoplasmic compartments. Efforts to bias Rev's trafficking either into or out of the nucleus revealed that Rev encoding a second CRM1 binding domain (Rev-2xNES) or Rev-dependent viral gag-pol mRNAs bearing tandem RREs (GP-2xRRE), rescue virus particle production in murine cells even in the absence of hCRM1. Combined, these results suggest a model wherein Rev-associated nuclear export signals cooperate to regulate the number or quality of CRM1's interactions with viral Rev/RRE ribonucleoprotein complexes in the nucleus. This mechanism regulates CRM1-dependent viral gene expression and is a determinant of HIV-1's capacity to produce virions in nonhuman cell types. IMPORTANCE Cells derived from mice and other nonhuman species exhibit profound blocks to HIV-1 replication. Here we elucidate a block to HIV-1 gene expression attributable to the murine version of the CRM1 (mCRM1) nuclear export receptor. In human cells, hCRM1 regulates the nuclear export of viral intron-containing mRNAs through the activity of the viral Rev

  17. Opposing roles of nuclear receptor HNF4α isoforms in colitis and colitis-associated colon cancer

    PubMed Central

    Chellappa, Karthikeyani; Deol, Poonamjot; Evans, Jane R; Vuong, Linh M; Chen, Gang; Briançon, Nadege; Bolotin, Eugene; Lytle, Christian; Nair, Meera G; Sladek, Frances M

    2016-01-01

    HNF4α has been implicated in colitis and colon cancer in humans but the role of the different HNF4α isoforms expressed from the two different promoters (P1 and P2) active in the colon is not clear. Here, we show that P1-HNF4α is expressed primarily in the differentiated compartment of the mouse colonic crypt and P2-HNF4α in the proliferative compartment. Exon swap mice that express only P1- or only P2-HNF4α have different colonic gene expression profiles, interacting proteins, cellular migration, ion transport and epithelial barrier function. The mice also exhibit altered susceptibilities to experimental colitis (DSS) and colitis-associated colon cancer (AOM+DSS). When P2-HNF4α-only mice (which have elevated levels of the cytokine resistin-like β, RELMβ, and are extremely sensitive to DSS) are crossed with Retnlb-/- mice, they are rescued from mortality. Furthermore, P2-HNF4α binds and preferentially activates the RELMβ promoter. In summary, HNF4α isoforms perform non-redundant functions in the colon under conditions of stress, underscoring the importance of tracking them both in colitis and colon cancer. DOI: http://dx.doi.org/10.7554/eLife.10903.001 PMID:27166517

  18. Spotlight: David Wood, MD, MSc, FRCP, FESC. A journey from a remote area of Scotland to the capital of the United Kingdom. Interview by Hannah Brown.

    PubMed

    Wood, David

    2007-12-01

    The death of an ambulance driver prompted David Wood, MD, MSc, FRCP, FESC, now Garfield Weston Professor of Cardiovascular Medicine at Imperial College, London, United Kingdom, to pursue cardiology as a career.

  19. David L. Parkhurst as the recipient of the 2012 O.E. Meinzer Award of the Hydrogeology Division of the Geological Society of America

    USGS Publications Warehouse

    Glynn, Pierre D.

    2012-01-01

    Describes the impact of USGS scientist David Parkhurst's influential contributions to the fields of aqueous geochemistry and hydrogeology. Parkhurst is the recipient of the 2012 O.E. Meinzer award of the Geological Society of America's Hydrogeology Division.

  20. A rendezvous with the queen of ion channels: Three decades of ion channel research by David T Yue and his Calcium Signals Laboratory

    PubMed Central

    Dick, Ivy E; Limpitikul, Worawan B; Niu, Jacqueline; Banerjee, Rahul; Issa, John B; Ben-Johny, Manu; Adams, Paul J; Kang, Po Wei; Lee, Shin Rong; Sang, Lingjie; Yang, Wanjun; Babich, Jennifer; Zhang, Manning; Bazazzi, Hojjat; Yue, Nancy C; Tomaselli, Gordon F

    2016-01-01

    David T. Yue was a renowned biophysicist who dedicated his life to the study of Ca2+ signaling in cells. In the wake of his passing, we are left not only with a feeling of great loss, but with a tremendous and impactful body of work contributed by a remarkable man. David's research spanned the spectrum from atomic structure to organ systems, with a quantitative rigor aimed at understanding the fundamental mechanisms underlying biological function. Along the way he developed new tools and approaches, enabling not only his own research but that of his contemporaries and those who will come after him. While we cannot hope to replicate the eloquence and style we are accustomed to in David's writing, we nonetheless undertake a review of David's chosen field of study with a focus on many of his contributions to the calcium channel field. PMID:26176690

  1. Involvement of elevated expression of multiple cell-cycle regulator, DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells.

    PubMed

    Ueki, T; Nishidate, T; Park, J H; Lin, M L; Shimo, A; Hirata, K; Nakamura, Y; Katagiri, T

    2008-09-25

    To investigate the detailed molecular mechanism of mammary carcinogenesis and discover novel therapeutic targets, we previously analysed gene expression profiles of breast cancers. We here report characterization of a significant role of DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein) in mammary carcinogenesis. Semiquantitative RT-PCR and northern blot analyses confirmed upregulation of DTL/RAMP in the majority of breast cancer cases and all of breast cancer cell lines examined. Immunocytochemical and western blot analyses using anti-DTL/RAMP polyclonal antibody revealed cell-cycle-dependent localization of endogenous DTL/RAMP protein in breast cancer cells; nuclear localization was observed in cells at interphase and the protein was concentrated at the contractile ring in cytokinesis process. The expression level of DTL/RAMP protein became highest at G(1)/S phases, whereas its phosphorylation level was enhanced during mitotic phase. Treatment of breast cancer cells, T47D and HBC4, with small-interfering RNAs against DTL/RAMP effectively suppressed its expression and caused accumulation of G(2)/M cells, resulting in growth inhibition of cancer cells. We further demonstrate the in vitro phosphorylation of DTL/RAMP through an interaction with the mitotic kinase, Aurora kinase-B (AURKB). Interestingly, depletion of AURKB expression with siRNA in breast cancer cells reduced the phosphorylation of DTL/RAMP and decreased the stability of DTL/RAMP protein. These findings imply important roles of DTL/RAMP in growth of breast cancer cells and suggest that DTL/RAMP might be a promising molecular target for treatment of breast cancer.

  2. An Assessment of the Current Day Impact of Various Materials Associated with the U.S. Nuclear Test Program in the Marshall Island

    SciTech Connect

    Robison, W L; Noshkin, V E; Hamilton, T F; Conrado, C L; Bogen, K T

    2001-05-01

    Different stable elements, and some natural and man-made radionuclides, were used as tracers or associated in other ways with nuclear devices that were detonated at Bikini and Enewetak Atolls as part of the U.S. nuclear testing program from 1946 through 1958. The question has been raised whether any of these materials dispersed by the explosions could be of sufficient concentration in either the marine environment or on the coral islands to be of a health concern to people living, or planning to live, on the atolls. This report addresses that concern. An inventory of the materials involved during the test period was prepared and provided to us by the Office of Defense Programs (DP) of the United States Department of Energy (DOE). The materials that the DOE and the Republic of the Marshall Islands (RMI) ask to be evaluated are--sulfur, arsenic, yttrium, tantalum, gold, rhodium, indium, tungsten, thallium, thorium-230,232 ({sup 230,232}Th), uranium-233,238 ({sup 233,238}U), polonium-210 ({sup 210}Po), curium-232 ({sup 232}Cu), and americium-241 ({sup 241}Am). The stable elements were used primarily as tracers for determining neutron energy and flux, and for other diagnostic purposes in the larger yield, multistage devices. It is reasonable to assume that these materials would be distributed in a similar manner as the fission products subsequent to detonation. A large inventory of fission product and uranium data was available for assessment. Detailed calculations show only a very small fraction of the fission products produced during the entire test series remain at the test site atolls. Consequently, based on the information provided, we conclude that the concentration of these materials in the atoll environment pose no adverse health effects to humans.

  3. Kaposi's sarcoma-associated herpesvirus noncoding polyadenylated nuclear RNA interacts with virus- and host cell-encoded proteins and suppresses expression of genes involved in immune modulation.

    PubMed

    Rossetto, Cyprian C; Pari, Gregory S

    2011-12-01

    During lytic infection, Kaposi's sarcoma-associated herpesvirus (KSHV) expresses a polyadenylated nuclear RNA (PAN RNA). This noncoding RNA (ncRNA) is localized to the nucleus and is the most abundant viral RNA during lytic infection; however, to date, the role of PAN RNA in the virus life cycle is unknown. Many examples exist where ncRNAs have a defined key regulatory function controlling gene expression by various mechanisms. Our goal for this study was to identify putative binding partners for PAN RNA in an effort to elucidate a possible function for the transcript in KSHV infection. We employed an in vitro affinity protocol where PAN RNA was used as bait for factors present in BCBL-1 cell nuclear extract to show that PAN RNA interacts with several virus- and host cell-encoded factors, including histones H1 and H2A, mitochondrial and cellular single-stranded binding proteins (SSBPs), and interferon regulatory factor 4 (IRF4). RNA chromatin immunoprecipitation (ChIP) assays confirmed that PAN RNA interacted with these factors in the infected cell environment. A luciferase reporter assay showed that PAN RNA expression interfered with the ability of IRF4/PU.1 to activate the interleukin-4 (IL-4) promoter, strongly suggesting a role for PAN RNA in immune modulation. Since the proteomic screen and functional data suggested a role in immune responses, we investigated if constitutive PAN RNA expression could affect other genes involved in immune responses. PAN RNA expression decreased expression of gamma interferon, interleukin-18, alpha interferon 16, and RNase L. These data strongly suggest that PAN RNA interacts with viral and cellular proteins and can function as an immune modulator. PMID:21957289

  4. Expression of a chimeric helix-loop-helix gene, Id-SCL, in K562 human leukemic cells is associated with nuclear segmentation.

    PubMed Central

    Goldfarb, A. N.; Wolf, M. L.; Greenberg, J. M.

    1992-01-01

    We have designed a chimeric gene, Id-SCL, in which the 3' helix-loop-helix encoding portion of the presumptive oncogene SCL/tal is joined to the 5' coding portion of Id, an inhibitory helix-loop-helix gene. The predicted protein product of this chimeric gene contains the helix-loop-helix dimerization domain of SCL/tal, but, lacking a basic DNA binding domain, is predicted to have the inhibitory function of the Id product. Expression of the Id-SCL fusion gene in stably transfected K562 cells reproducibly resulted in nuclear segmentation and depressed growth rates; both of these phenotypic effects demonstrated a dosage dependence on the levels of Id-SCL mRNA and protein expressed in the various clones. Electron microscopy of cells expressing high levels of Id-SCL mRNA showed a significant increase in cytoplasmic perinuclear thin filaments and diminution of marginal heterochromatin in the nuclei. No other changes in hematopoietic differentiation status were observed in association with Id-SCL expression. Expression of intact Id and SCL/tal genes, as well as deletion mutants of Id and SCL/tal, independently transfected into K562 cells, indicated that the nuclear segmentation effect is dependent on the presence of a protein possessing a helix-loop-helix domain but lacking a basic domain. Our studies suggest that the balance of transcriptional inhibitory and stimulatory helix-loop-helix proteins in cells may be important determinants of proliferation and of structural organization within cells. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 8 Figure 11 PMID:1443047

  5. Atypical Cell Populations Associated with Acquired Resistance to Cytostatics and Cancer Stem Cell Features: The Role of Mitochondria in Nuclear Encapsulation

    PubMed Central

    Gustmann, Sebastian; Jastrow, Holger; Acikelli, Ali Haydar; Dammann, Philip; Klein, Jacqueline; Dembinski, Ulrike; Bardenheuer, Walter; Malak, Sascha; Araúzo-Bravo, Marcos J.; Schultheis, Beate; Aldinger, Constanze; Strumberg, Dirk

    2014-01-01

    Until recently, acquired resistance to cytostatics had mostly been attributed to biochemical mechanisms such as decreased intake and/or increased efflux of therapeutics, enhanced DNA repair, and altered activity or deregulation of target proteins. Although these mechanisms have been widely investigated, little is known about membrane barriers responsible for the chemical imperviousness of cell compartments and cellular segregation in cytostatic-treated tumors. In highly heterogeneous cross-resistant and radiorefractory cell populations selected by exposure to anticancer agents, we found a number of atypical recurrent cell types in (1) tumor cell cultures of different embryonic origins, (2) mouse xenografts, and (3) paraffin sections from patient tumors. Alongside morphologic peculiarities, these populations presented cancer stem cell markers, aberrant signaling pathways, and a set of deregulated miRNAs known to confer both stem-cell phenotypes and highly aggressive tumor behavior. The first type, named spiral cells, is marked by a spiral arrangement of nuclei. The second type, monastery cells, is characterized by prominent walls inside which daughter cells can be seen maturing amid a rich mitochondrial environment. The third type, called pregnant cells, is a giant cell with a syncytium-like morphology, a main nucleus, and many endoreplicative functional progeny cells. A rare fourth cell type identified in leukemia was christened shepherd cells, as it was always associated with clusters of smaller cells. Furthermore, a portion of resistant tumor cells displayed nuclear encapsulation via mitochondrial aggregation in the nuclear perimeter in response to cytostatic insults, probably conferring imperviousness to drugs and long periods of dormancy until nuclear eclosion takes place. This phenomenon was correlated with an increase in both intracellular and intercellular mitochondrial traffic as well as with the uptake of free extracellular mitochondria. All these cellular

  6. Osteopontin is associated with nuclear factor {kappa}B gene expression during tail-suspension-induced bone loss

    SciTech Connect

    Ishijima, Muneaki; Ezura, Yoichi . E-mail: ezura.mph@mril.tmd.ac.jp; Tsuji, Kunikazu

    2006-10-01

    Osteoporosis due to unloading-induced bone loss is a critical issue in the modern aging society. Although the mechanisms underlying this phenomenon are largely unknown, osteopontin (OPN) is one of the critical mediators required for unloading-induced bone loss [M. Ishijima, S.R. Rittling, T. Yamashita, K. Tsuji, H. Kurosawa, A. Nifuji, D.T. Denhardt, and M. Noda, Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin, J Exp Med, 193 (2001) 399-404]. To clarify the molecular bases for OPN actions, we carried out microarray analyses on the genes expressed in the femoral bone marrow cells in wild type and OPN-/- mice. The removal of the mechanical load induced bone loss in wild type, but not in OPN-/- mice, as previously reported. Expression analysis of 9586 cDNAs on a microarray system revealed that OPN deficiency blocked tail-suspension-induced expression of ten genes (group A). This observation was confirmed based on semi-quantitative RT-PCR analyses. On the other hand, expression of four genes (group B) was not altered by tail suspension in wild type but was enhanced in OPN-deficient mice. NF-{kappa}B p105 subunit gene (Nfkb1) was found in group A and Bax in group B. p53 gene expression was upregulated by tail suspension in wild type mice, but it was no longer observed in OPN-/- mice. These data indicate that OPN acts to mediate mechanical stress signaling upstream to the genes encoding apoptosis-related molecules, and its action is associated with alteration of the genes.

  7. Evaluation of the function of the human apolipoprotein B gene nuclear matrix association regions in transgenic mice.

    PubMed

    Wang, D M; Taylor, S; Levy-Wilson, B

    1996-10-01

    The human apolipoprotein B (apoB) gene resides in a 47.5 kb DNasel-sensitive chromosomal domain in hepatic and intestinal cells, flanked by the 5' distal matrix association region (MAR) and the 3' proximal MAR. A third MAR, the 5' proximal MAR, is found only in transcriptionally active hepatic (HepG2) cells. Hepatic expression of the apoB gene requires a tissue-specific promoter (-898 to +121) and an enhancer from the second intron of the gene (+360 to +1064). A vector containing this portion of the gene linked to the beta-galactosidase reporter is sufficient for low level expression in the livers of transgenic mice. Expression in transgenic mice was increased when the promoter-enhancer beta-gal vector was flanked by MARs. The results were similar whether the 5' distal, the 5' proximal or the 3' proximal MARs were placed at both ends of the construct, or whether the construct was flanked by the 5' distal and the 3' MAR, suggesting that the apoB MARs play a role in gene expression in vivo. When the MAR-containing constructs were transiently transfected into HepG2 cells, the resulting beta-gal activities were similar to that of the construct lacking MARs, thus demonstrating that the MARs do not exhibit any enhancer activity. Recent experiments (Kalos, M., and R. E. K. Fournier. 1995. Mol. Cell. Biol. 15: 198-207) examining stable integration of some of our constructs into human and rat hepatoma transfectants suggest that in single and double copy transfectants, the apoB MARs behave as boundary "insulators", protecting the integrated transgenes against position effects regardless of their site of integration. However, multicopy transfectants are transcriptionally inactive and when the MARs are absent, expression of the transgenes drops to background levels. Our results to date with single and low-copy number transgenes do not support an insulator function for the apoB MARs, although they appear to be required to increase the levels of expression.

  8. Nuclear reactor

    DOEpatents

    Wade, Elman E.

    1979-01-01

    A nuclear reactor including two rotatable plugs and a positive top core holddown structure. The top core holddown structure is divided into two parts: a small core cover, and a large core cover. The small core cover, and the upper internals associated therewith, are attached to the small rotating plug, and the large core cover, with its associated upper internals, is attached to the large rotating plug. By so splitting the core holddown structures, under-the-plug refueling is accomplished without the necessity of enlarging the reactor pressure vessel to provide a storage space for the core holddown structure during refueling. Additionally, the small and large rotating plugs, and their associated core covers, are arranged such that the separation of the two core covers to permit rotation is accomplished without the installation of complex lifting mechanisms.

  9. Nuclear rights - nuclear wrongs

    SciTech Connect

    Paul, E.F.; Miller, F.D.; Paul, J.; Ahrens, J.

    1986-01-01

    This book contains 11 selections. The titles are: Three Ways to Kill Innocent Bystanders: Some Conundrums Concerning the Morality of War; The International Defense of Liberty; Two Concepts of Deterrence; Nuclear Deterrence and Arms Control; Ethical Issues for the 1980s; The Moral Status of Nuclear Deterrent Threats; Optimal Deterrence; Morality and Paradoxical Deterrence; Immoral Risks: A Deontological Critique of Nuclear Deterrence; No War Without Dictatorship, No Peace Without Democracy: Foreign Policy as Domestic Politics; Marxism-Leninism and its Strategic Implications for the United States; Tocqueveille War.

  10. Eponymous doctors associated with Edinburgh, Part 2--David Bruce, John Cheyne, William Stokes, Alexander Monro Secundus, Joseph Gamgee.

    PubMed

    Doyle, D

    2006-12-01

    This, the second in a three-paper series with this title, looks at famous doctors who trained in Edinburgh and their eponyms. With one possible exception, none seems to have sought the eponym, nor awarded it to themselves, nor used it for self-promotion. Unlike those in the first paper, all eponyms in this paper are still in use and their brevity is in contrast to the lengthy description needed if the eponym is not used. Examples are Cheyne-Stokes respiration, Stokes-Adam attacks, Brucellosis and Gamgee dressing. Monro Secundus is included because of his vehement defence of his professional reputation and research findings when he suspected others of trying to detract credit from him, a characteristic seldom reported for the others. PMID:17526135

  11. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. PMID:27114368

  12. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system.

  13. Nuclear security

    SciTech Connect

    Dingell, J.D.

    1991-02-01

    The Department of Energy's (DOE) Lawrence Livermore National Laboratory, located in Livermore, California, generates and controls large numbers of classified documents associated with the research and testing of nuclear weapons. Concern has been raised about the potential for espionage at the laboratory and the national security implications of classified documents being stolen. This paper determines the extent of missing classified documents at the laboratory and assesses the adequacy of accountability over classified documents in the laboratory's custody. Audit coverage was limited to the approximately 600,000 secret documents in the laboratory's custody. The adequacy of DOE's oversight of the laboratory's secret document control program was also assessed.

  14. Talk About Nuclear Power

    ERIC Educational Resources Information Center

    Tremlett, Lewis

    1976-01-01

    Presents an overview of the relation of nuclear power to human health and the environment, and discusses the advantages and disadvantages of nuclear power as an energy source urging technical educators to inculcate an awareness of the problems associated with the production of energy. Describes the fission reaction process, the hazards of…

  15. Nuclear Power Plant Technician

    ERIC Educational Resources Information Center

    Randall, George A.

    1975-01-01

    The author recognizes a body of basic knowledge in nuclear power plant technoogy that can be taught in school programs, and lists the various courses, aiming to fill the anticipated need for nuclear-trained manpower--persons holding an associate degree in engineering technology. (Author/BP)

  16. LETTER REPORT. INDEPENDENT CONFIRMATORY SURVEY RESULTS OF SOILS ASSOCIATED WITH THE ARGYLE STREET SEWER LINE AT THE UNITED NUCLEAR CORPORATION NAVAL PRODUCTS SITE, NEW HAVEN, CONNECTICUT

    SciTech Connect

    Adams, Wade C.

    2012-01-24

    Oak Ridge Institute for Science and Education (ORISE) personnel visited the United Nuclear Corporation (UNC) Naval Products site on three separate occasions during the months of October and November 2011. The purpose of these visits was to conduct confirmatory surveys of soils associated with the Argyle Street sewer line that was being removed. Soil samples were collected from six different, judgmentally determined locations in the Argyle Street sewer trench. In addition to the six soil samples collected by ORISE, four replicate soil samples were collected by Cabrera Services, Inc. (CSI) for analysis by the ORISE laboratory. Replicate samples S0010 and S0011 were final status survey (FSS) bias samples; S0012 was an FSS systematic sample; and S0015 was a waste characterization sample. Six soil samples were also collected for background determination. Uranium-235 and uranium-238 concentrations were determined via gamma spectroscopy; the spectra were also reviewed for other identifiable photopeaks. Radionuclide concentrations for these soil samples are provided. In addition to the replicate samples and the samples collected by ORISE, CSI submitted three soil samples for inter-laboratory comparison analyses. One sample was from the background reference area, one was from waste characterization efforts (material inside the sewer line), and one was a FSS sample. The inter-laboratory comparison analyses results between ORISE and CSI were in agreement, except for one sample collected in the reference area. Smear results For Argyle Street sewer pipes are tabulated.

  17. Lack of Association between Nuclear Factor Erythroid-Derived 2-Like 2 Promoter Gene Polymorphisms and Oxidative Stress Biomarkers in Amyotrophic Lateral Sclerosis Patients

    PubMed Central

    Chico, Lucia; Borgia, Loredana; Rocchi, Anna; D'Amelio, Antonia; Carlesi, Cecilia; Mancuso, Michelangelo; Siciliano, Gabriele

    2014-01-01

    Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The intracellular redox balance is finely modulated by numerous complex mechanisms critical for cellular functions, among which the nuclear factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a cohort of ALS patients (n = 145) and healthy controls (n = 168), three SNPs in Nrf2 gene promoter: −653 A/G, −651 G/A, and −617 C/A and evaluated, in a subset (n = 73) of patients, advanced oxidation protein products (AOPP), iron-reducing ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral biomarkers. Nrf2 polymorphisms were not different among patients and controls. Increased levels of AOPP (P < 0.05) and decreased levels of FRAP (P < 0.001) have been observed in ALS patients compared with controls, but no difference in -SH values was found. Furthermore, no association was found between biochemical markers of redox balance and Nrf2 polymorphisms. These data confirm an altered redox balance in ALS and indicate that, while being abnormally modified compared to controls, the oxidative stress biomarkers assessed in this study are independent from the −653 A/G, −651 G/A, and −617 C/A Nrf2 SNPs in ALS patients. PMID:24672634

  18. Lack of association between nuclear factor erythroid-derived 2-like 2 promoter gene polymorphisms and oxidative stress biomarkers in amyotrophic lateral sclerosis patients.

    PubMed

    LoGerfo, Annalisa; Chico, Lucia; Borgia, Loredana; Petrozzi, Lucia; Rocchi, Anna; D'Amelio, Antonia; Carlesi, Cecilia; Caldarazzo Ienco, Elena; Mancuso, Michelangelo; Siciliano, Gabriele

    2014-01-01

    Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The intracellular redox balance is finely modulated by numerous complex mechanisms critical for cellular functions, among which the nuclear factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a cohort of ALS patients (n = 145) and healthy controls (n = 168), three SNPs in Nrf2 gene promoter: -653 A/G, -651 G/A, and -617 C/A and evaluated, in a subset (n = 73) of patients, advanced oxidation protein products (AOPP), iron-reducing ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral biomarkers. Nrf2 polymorphisms were not different among patients and controls. Increased levels of AOPP (P < 0.05) and decreased levels of FRAP (P < 0.001) have been observed in ALS patients compared with controls, but no difference in -SH values was found. Furthermore, no association was found between biochemical markers of redox balance and Nrf2 polymorphisms. These data confirm an altered redox balance in ALS and indicate that, while being abnormally modified compared to controls, the oxidative stress biomarkers assessed in this study are independent from the -653 A/G, -651 G/A, and -617 C/A Nrf2 SNPs in ALS patients. PMID:24672634

  19. Clinical use of quantitative cardiac perfusion PET: rationale, modalities and possible indications. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM).

    PubMed

    Sciagrà, Roberto; Passeri, Alessandro; Bucerius, Jan; Verberne, Hein J; Slart, Riemer H J A; Lindner, Oliver; Gimelli, Alessia; Hyafil, Fabien; Agostini, Denis; Übleis, Christopher; Hacker, Marcus

    2016-07-01

    Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

  20. Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma.

    PubMed

    Bitgen, N; Donmez-Altuntas, H; Bayram, F; Cakir, I; Hamurcu, Z; Diri, H; Baskol, G; Senol, S; Durak, A C

    2016-01-01

    Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically significant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.