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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

    ... Federal Energy Regulatory Commission David E. Cereghino, Idaho County Light & Power Cooperative... 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. David Scott

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Dr. David R. Scott was appointed Director of NASA's Flight Research Center on April 18, 1975. From August 1973 he served as Deputy Director of FRC and was appointed acting director in January 1975. He is retired from the U.S. Air Force where he held the rank of Colonel. Dave left the NASA Dryden Flight Research Center on October 30, 1977 after the Center had been renamed in honor of Hugh L. Dryden. As a NASA astronaut, Scott flew on Gemini 8, Apollo 9 and was spacecraft commander of Apollo 15. When he left the astronaut corps in 1972, Scott was named Technical Assistant to the Apollo Program Manager at Johnson Space Center in Houston. Later he served as Special Assistant for Mission Operations and Government Funded Equipment. Dave earned a Bachelor of Science Degree from the United States Military Academy in 1954, standing fifth in a class of 633, and the degrees of Bachelor and Master of Science in Aeronautics and Astronautics from the Massachusetts Institute of Technology (MIT) in 1962. He was awarded an Honorary Doctorate of Astronautical Science from the University of Michigan in 1971. Dave has graduated from the Air Force Experimental Test Pilot School and Aerospace Research Pilot School. He has over 5,600 hours flying time along with 20 hours of extra vehicular activity (EVA) time. Dr. Scott is a Fellow of the American Astronautical Society; Associate Fellow of the American Institute of Aeronautics and Astronautics; a member of the Society of Experimental Test Pilots, Tau Beta Pi, Sigma Xi, and Sigma Gamma Tau. Among Dr. Scott's special honors are two NASA Distinguished Service Medals, the NASA Exceptional Service Medal, two Air Force Distinguished Service Medals, the Air Force Distinguished Flying Cross, the Air Force Association's David C. Schilling Trophy, and the Robert J. Collier Trophy for 1971.

  3. 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…

  4. 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…

  5. 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.

  6. David Macaulay's Pyramid.

    ERIC Educational Resources Information Center

    Frew, Andrew W.

    1997-01-01

    Integrating literature and mathematics can be meaningful using David Macaulay's "Pyramid." This article provides an annotated bibliography of picture books, fiction, folk tales, nonfiction, videotapes, audio books, and CD-ROMs for grades 1-12 to support a unit on Egypt. Describes related math activities; and highlights a catalog of…

  7. Recollections of David Marr.

    PubMed

    Nishihara, H K

    2012-01-01

    David Marr came to MIT's Artificial Intelligence (AI) Lab in the early 1970s and energized the study of vision at the intersection of computer science, psychology, and neuroscience. As one of his first graduate students, I had the privilege of getting to know him and working with him during that heady period of AI research.

  8. 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.

  9. 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…

  10. 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

  11. 77 FR 66581 - Notice of Renewal of the Civil Nuclear Trade Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-06

    ... associations from across the United States' civil nuclear supply chain. Dated: October 31, 2012. Edward A. O... 20230; phone 202- 482-1706 or email David.Kincaid@trade.gov . SUPPLEMENTARY INFORMATION: The...

  12. Laurance David Hall.

    PubMed

    Coxon, Bruce

    2011-01-01

    An account is given of the life, scientific contributions, and passing of Laurance David Hall (1938-2009), including his early history and education at the University of Bristol, UK, and the synthesis and NMR spectroscopy of carbohydrates and other natural products during ∼20 years of research and teaching at the University of British Columbia in Vancouver, Canada. Lists of graduate students, post-doctoral fellows, and sabbatical visitors are provided for this period. Following a generous endowment by Dr. Herchel Smith, Professor Hall built a new Department of Medicinal Chemistry at Cambridge University, UK, and greatly expanded his researches into the technology and applications of magnetic resonance imaging (MRI) and zero quantum NMR. MRI technology was applied both to medical problems such as the characterization of cartilage degeneration in knee joints, the measurement of ventricular function, lipid localization in animal models of atherosclerosis, paramagnetic metal complexes of polysaccharides as contrast agents, and studies of many other anatomical features, but also to several aspects of materials analysis, including food analyses, process control, and the elucidation of such physical phenomena as the flow of liquids through porous media, defects in concrete, and the visualization of fungal damage to wood. Professor Hall's many publications, patents, lectures, and honors and awards are described, and also his successful effort to keep the Asilomar facility in Pacific Grove, California as the alternating venue for the annual Experimental NMR Conference. Two memorial services for Professor Hall are remembered.

  13. 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.

  14. 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."...

  15. 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...

  16. 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.

  17. A novel family of plant nuclear envelope-associated proteins.

    PubMed

    Pawar, Vidya; Poulet, Axel; Détourné, Gwénaëlle; Tatout, Christophe; Vanrobays, Emmanuel; Evans, David E; Graumann, Katja

    2016-10-01

    This paper describes the characterisation of a new family of higher plant nuclear envelope-associated proteins (NEAPs) that interact with other proteins of the nuclear envelope. In the model plant Arabidopsis thaliana, the family consists of three genes expressed ubiquitously (AtNEAP1-3) and a pseudogene (AtNEAP4). NEAPs consist of extensive coiled-coil domains, followed by a nuclear localisation signal and a C-terminal predicted transmembrane domain. Domain deletion mutants confirm the presence of a functional nuclear localisation signal and transmembrane domain. AtNEAP proteins localise to the nuclear periphery as part of stable protein complexes, are able to form homo- and heteromers, and interact with the SUN domain proteins AtSUN1 and AtSUN2, involved in the linker of nucleoskeleton and cytoskeleton (LINC) complex. An A. thaliana cDNA library screen identified a putative transcription factor called AtbZIP18 as a novel interactor of AtNEAP1, which suggest a connection between NEAP and chromatin. An Atneap1 Atneap3 double-knockout mutant showed reduced root growth, and altered nuclear morphology and chromatin structure. Thus AtNEAPs are suggested as inner nuclear membrane-anchored coiled-coil proteins with roles in maintaining nuclear morphology and chromatin structure.

  18. 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…

  19. A Reply from David Elkind.

    ERIC Educational Resources Information Center

    Elkind, David

    1989-01-01

    Replying to Robert H. Anderson's article in the same "Principal" issue, David Elkind defends his article against classroom rotation. Elkind strongly favors multiage grouping and team teaching, but views the real issue as departmentalization and rotation versus self-contained classrooms. Although multiage grouping and team teaching are…

  20. The association between nuclear receptors and ocular diseases.

    PubMed

    Liu, Ke; Zou, Chang; Qin, Bo

    2017-02-07

    Nuclear hormone receptors (NRs) are one of the most abundant transcription factors in the human cells. They regulate expression of genes via interactions with corresponding ligands, co-activators, and co-repressors. These molecular pathways play important roles in the development, cell differentiation, and physiologic and metabolic processes. Increasingly, targeting nuclear receptors is becoming a promising strategy for new drug development. The aim of this review is to discuss the association between nuclear receptors and eye development, and expand their role in various ocular diseases such as keratitis, cataract, glaucoma, uveitis, retinopathy, and ophthalmic tumors. Recent studies in this area are highlighted as well as future research directions and potential clinical applications. Finally, various strategies will be elucidated to inspire more targeted therapies for ocular diseases through the use of nuclear receptors.

  1. TTRAP is a novel PML nuclear bodies-associated protein

    SciTech Connect

    Xu Guanlan; Pan Yukun; Wang Bingyin; Huang Lu; Tian Ling; Xue Jinglun; Chen Jinzhong Jia, William

    2008-10-24

    PML nuclear body (PML NB) is an important macromolecular nuclear structure that is involved in many essential aspects of cellular function. Tens of proteins have been found in PML NBs, and promyelocytic leukemia protein (PML) has been proven to be essential for the formation of this structure. Here, we showed that TRAF and TNF receptor-associated protein (TTRAP) was a novel PML NBs-associated protein. TTRAP colocalized with three important PML NBs-associated proteins, PML, DAXX and Sp100 in the typical fashion of PML NBs. By yeast mating assay, TTRAP was identified to interact with these PML NBs-associated proteins. The transcription and expression of TTRAP could be induced by IFN-{gamma}, representing another common feature of PML NBs-associated proteins. These results would not only be important for understanding PML NBs but also be helpful in studying the TTRAP function in the future.

  2. Human Leukemia-Associated Anti-Nuclear Reactivity

    PubMed Central

    Klein, George; Steiner, Melita; Wiener, Francis; Klein, Eva

    1974-01-01

    A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological specificity and morphological appearance, although it is visualized by the same method. Serum from acute myeloid leukemia patients gave positive reactions in 73% of the cases. In acute lymphatic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, and Burkitt's lymphoma the sera were positive in 35, 14, 19, and 24%, respectively. Two of five polycythemia and two of eleven myeloma sera were also positive. Among 61 healthy controls, 58 were negative, whereas three showed a diffuse nuclear staining with a different pattern. Among 24 carcinoma patients, 18 were negative, whereas six gave a nuclear staining with a different, diffuse pattern. Sera from 20 patients who had recovered from infectious mononucleosis were all negative. In addition to the blasts of acute myeloid leukemia, a similar reactivity was seen with two Epstein-Barr virus DNA and EBNA-negative African lymphoma biopsies and in a short-lived tissue culture line derived from one of them. LANA could be a fetal or tissue-specific antigen, a virally determined antigen, or a specific form of anti-nuclear reactivity. Images PMID:4595570

  3. Honoring Jean-David Rochaix.

    PubMed

    Govindjee; Redding, Kevin

    2017-02-01

    We honor Jean-David Rochaix, an outstanding scholar of chloroplast biogenesis and photosynthesis, who received the prestigious Lifetime Achievement Award of the International Society of Photosynthesis Research at its 17th International Photosynthesis Congress held in Maastricht, The Netherlands (August 5-12, 2016). With this award he joins other major discoverers in the field of photosynthesis: Pierre Joliot (of France, 2013); Ulrich W. Heber* (of Germany, 2010) and Kenneth Sauer (of USA, 2010); Jan M. Anderson* (of Australia, 2007); and Horst T. Witt* (of Germany, 2004). See "Appendix 1" for the list of those who have received the ISPR Communication, Innovation, Calvin-Benson, and Hill awards.

  4. 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…

  5. Structure and Function of Latency-Associated Nuclear Antigen

    PubMed Central

    Verma, S. C.; Lan, K.

    2011-01-01

    Latency-associated nuclear antigen (LANA) encoded by open reading frame 73 (ORF73) is the major latent protein expressed in all forms of KSHV-associated malignancies. LANA is a large (222–234 kDa) nuclear protein that interacts with various cellular as well as viral proteins. LANA has been classified as an oncogenic protein as it dysregulates various cellular pathways including tumor suppressor pathways associated with pRb and p53 and can transform primary rat embryo fibroblasts in cooperation with the cellular oncogene Hras. It associates with GSK-3β, an important modulator of Wnt signaling pathway leading to the accumulation of cytoplasmic β-catenin, which upregulates Tcf/Lef regulated genes after entering into the nucleus. LANA also blocks the expression of RTA, the reactivation transcriptional activator, which is critical for the latency to lytic switch, and thus helps in maintaining viral latency. LANA tethers the viral episomal DNA to the host chromosomes by directly binding to its cognate binding sequence within the TR region of the genome through its C terminus and to the nucleosomes through the N terminus of the molecule. Tethering to the host chromosomes helps in efficient partitioning of the viral episomes in the dividing cells. Disruptions of LANA expression led to reduction in the episomal copies of the viral DNA, supporting its role in persistence of the viral DNA. The functions known so far suggest that LANA is a key player in KSHV-mediated pathogenesis. PMID:17089795

  6. 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.

  7. [Book review] Green engineering: environmentally conscious design, by David T. Allen and David R. Shonnard

    USGS Publications Warehouse

    Boustany, R.G.

    2002-01-01

    Review of: Green engineering: Environmentally conscious design / David T. Allen and David R. Shonnard / Prentice-Hall, Inc., One Lake Street, Upper Saddle River, NJ 07458. 2002. 552 pages. ISBN 0-13-061908-6.

  8. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies.

    PubMed

    Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

    2015-03-21

    Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB's function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB's role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy.

  9. 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

  10. 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.

  11. 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.

  12. 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…

  13. Akinetic mutism and the story of David.

    PubMed

    Sinden, Rebecca; Wilson, Barbara A; Rose, Anita; Mistry, Nimisha

    2017-02-02

    Following a description about the characteristics of akinetic mutism (AM) and how it differs from locked-in syndrome (LIS) and a disorder of consciousness (DOC), we present the case of David, a 71-year-old man with AM. David sustained a stroke following a middle cerebral artery (MCA) thrombus. A CT scan at the time detected old ischaemic infarcts affecting the right frontal lobe, the left occipital lobe and the left parietal lobe so David had bilateral brain damage. Initially thought to have a DOC, further neuropsychological assessments administered when David had improved a little, resulted in the diagnosis of AM. Although David spoke little, when he did speak, his words and phrases were well articulated, grammatical and with appropriate intonation. He was alert and visually aware and he was not paralysed. We discuss whether the diagnosis was correct and address the difficulties in assessing such patients.

  14. Nuclear processes associated with plant immunity and pathogen susceptibility

    PubMed Central

    Motion, Graham B.; Amaro, Tiago M.M.M.; Kulagina, Natalja

    2015-01-01

    Plants are sessile organisms that have evolved exquisite and sophisticated mechanisms to adapt to their biotic and abiotic environment. Plants deploy receptors and vast signalling networks to detect, transmit and respond to a given biotic threat by inducing properly dosed defence responses. Genetic analyses and, more recently, next-generation -omics approaches have allowed unprecedented insights into the mechanisms that drive immunity. Similarly, functional genomics and the emergence of pathogen genomes have allowed reciprocal studies on the mechanisms governing pathogen virulence and host susceptibility, collectively allowing more comprehensive views on the processes that govern disease and resistance. Among others, the identification of secreted pathogen molecules (effectors) that modify immunity-associated processes has changed the plant–microbe interactions conceptual landscape. Effectors are now considered both important factors facilitating disease and novel probes, suited to study immunity in plants. In this review, we will describe the various mechanisms and processes that take place in the nucleus and help regulate immune responses in plants. Based on the premise that any process required for immunity could be targeted by pathogen effectors, we highlight and describe a number of functional assays that should help determine effector functions and their impact on immune-related processes. The identification of new effector functions that modify nuclear processes will help dissect nuclear signalling further and assist us in our bid to bolster immunity in crop plants. PMID:25846755

  15. 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.

  16. Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes.

    PubMed

    Rappa, Germana; Santos, Mark F; Green, Toni M; Karbanová, Jana; Hassler, Justin; Bai, Yongsheng; Barsky, Sanford H; Corbeil, Denis; Lorico, Aurelio

    2017-02-28

    Extracellular membrane vesicles (EVs) function as vehicles of intercellular communication, but how the biomaterials they carry reach the target site in recipient cells is an open question. We report that subdomains of Rab7+ late endosomes and nuclear envelope invaginations come together to create a sub-nuclear compartment, where biomaterials associated with CD9+ EVs are delivered. EV-derived biomaterials were also found in the nuclei of host cells. The inhibition of nuclear import and export pathways abrogated the nuclear localization of EV-derived biomaterials or led to their accumulation therein, respectively, suggesting that their translocation is dependent on nuclear pores. Nuclear envelope invagination-associated late endosomes were observed in ex vivo biopsies in both breast carcinoma and associated stromal cells. The transcriptome of stromal cells exposed to cancer cell-derived CD9+ EVs revealed that the regulation of eleven genes, notably those involved in inflammation, relies on the nuclear translocation of EV-derived biomaterials. Our findings uncover a new cellular pathway used by EVs to reach nuclear compartment.

  17. Heterogeneous distributed query processing: The DAVID system

    NASA Technical Reports Server (NTRS)

    Jacobs, Barry E.

    1985-01-01

    The objective of the Distributed Access View Integrated Database (DAVID) project is the development of an easy to use computer system with which NASA scientists, engineers and administrators can uniformly access distributed heterogeneous databases. Basically, DAVID will be a database management system that sits alongside already existing database and file management systems. Its function is to enable users to access the data in other languages and file systems without having to learn the data manipulation languages. Given here is an outline of a talk on the DAVID project and several charts.

  18. Polyadenylylated nuclear RNA encoded by Kaposi sarcoma-associated herpesvirus.

    PubMed Central

    Sun, R; Lin, S F; Gradoville, L; Miller, G

    1996-01-01

    A newly recognized gamma herpesvirus known as Kaposi sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is present in Kaposi sarcomas and body-cavity-based lymphomas. Here we identify a novel abundant 1.2-kb RNA, polyadenylated nuclear RNA (PAN RNA), encoded by the virus. The majority of cDNAs produced from poly(A)-selected RNA isolated from a human body cavity lymphoma cell line 48 hr after butyrate induction of KSHV lytic replication represented PAN RNA. Within PAN RNA were two 9 and 16 nt stretches with 89% and 94% identity to U1 RNA. A third stretch of 14 nt was 93% complementary to U1. The 5' upstream region of PAN RNA contained both proximal and distal sequence elements characteristic of regulatory regions of U snRNAs, whereas the 3' end was polyadenylylated. PAN RNA was transcribed by RNA polymerase II, lacked a trimethylguanosine cap, and did not associate with polyribosomes. PAN RNA formed a speckled pattern in the nucleus typical of U snRNAs and colocalized with Sm protein. Therefore, PAN represents a new type of RNA, possessing features of both U snRNA and mRNA. Images Fig. 2 Fig. 3 Fig. 4 PMID:8876232

  19. 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.

  20. Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene.

    PubMed Central

    DeHoratius, C; Silver, P A

    1996-01-01

    To identify components involved in nuclear protein import, we used a genetic selection to isolate mutants that mislocalized a nuclear-targeted protein. We identified temperature-sensitive mutants that accumulated several different nuclear proteins in the cytoplasm when shifted to the semipermissive temperature of 30 degrees C; these were termed npl (nuclear protein localization) mutants. We now present the properties of yeast strains bearing mutations in the NPL4 gene and report the cloning of the NPL4 gene and the characterization of the Np14 protein. The npl4-1 mutant was isolated by the previously described selection scheme. The second allele, npl4-2, was identified from an independently derived collection of temperature-sensitive mutants. The npl4-1 and npl4-2 strains accumulate nuclear-targeted proteins in the cytoplasm at the nonpermissive temperature consistent with a defect in nuclear protein import. Using an in vitro nuclear import assay, we show that nuclei prepared from temperature-shifted npl4 mutant cells are unable to import nuclear-targeted proteins, even in the presence of cytosol prepared from wild-type cells. In addition, npl4-2 cells accumulate poly(A)+ RNA in the nucleus at the nonpermissive temperature, consistent with a failure to export mRNA from the nucleus. The npl4-1 and npl4-2 cells also exhibit distinct, temperature-sensitive structural defects: npl4-1 cells project extra nuclear envelope into the cytoplasm, whereas npl4-2 cells from nuclear envelope herniations that appear to be filled with poly(A)+ RNA. The NPL4 gene encodes an essential M(r) 64,000 protein that is located at the nuclear periphery and localizes in a pattern similar to nuclear pore complex proteins. Taken together, these results indicate that this gene encodes a novel nuclear pore complex or nuclear pore complex-associated component required for nuclear membrane integrity and nuclear transport. Images PMID:8930904

  1. Dangers associated with civil nuclear power programmes: weaponization and nuclear waste.

    PubMed

    Boulton, Frank

    2015-07-24

    The number of nuclear power plants in the world rose exponentially to 420 by 1990 and peaked at 438 in 2002; but by 2014, as closed plants were not replaced, there were just 388. In spite of using more renewable energy, the world still relies on fossil fuels, but some countries plan to develop new nuclear programmes. Spent nuclear fuel, one of the most dangerous and toxic materials known, can be reprocessed into fresh fuel or into weapons-grade materials, and generates large amounts of highly active waste. This article reviews available literature on government and industry websites and from independent analysts on world energy production, the aspirations of the 'new nuclear build' programmes in China and the UK, and the difficulties in keeping the environment safe over an immense timescale while minimizing adverse health impacts and production of greenhouse gases, and preventing weaponization by non-nuclear-weapons states acquiring civil nuclear technology.

  2. 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)

  3. 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.

  4. Association of Chromosome Territories with the Nuclear Matrix

    PubMed Central

    Ma, Hong; Siegel, Alan J.; Berezney, Ronald

    1999-01-01

    To study the possible role of the nuclear matrix in chromosome territory organization, normal human fibroblast cells are treated in situ via classic isolation procedures for nuclear matrix in the absence of nuclease (e.g., DNase I) digestion, followed by chromosome painting. We report for the first time that chromosome territories are maintained intact on the nuclear matrix. In contrast, complete extraction of the internal nuclear matrix components with RNase treatment followed by 2 M NaCl results in the disruption of higher order chromosome territory architecture. Correlative with territorial disruption is the formation of a faint DNA halo surrounding the nuclear lamina and a dispersive effect on the characteristically discrete DNA replication sites in the nuclear interior. Identical results were obtained using eight different human chromosome paints. Based on these findings, we developed a fractionation strategy to release the bulk of nuclear matrix proteins under conditions where the chromosome territories are maintained intact. A second treatment results in disruption of the chromosome territories in conjunction with the release of a small subset of acidic proteins. These proteins are distinct from the major nuclear matrix proteins and may be involved in mediating chromosome territory organization. PMID:10444063

  5. The Emergence of the Nuclear Industry and Associated Crime

    DTIC Science & Technology

    1991-08-01

    was Martin Sobell, who was convicted and sentenced to thirty years in prison. He was confined for five years at Alcatraz and was later transferred to...Washington: GPO, 1973): 111-1. 11 Dan O’Niel, "Project Chariot: How Alaska Escaped Nuclear Excavation," The Bulletin of thg Atomic Scientists 45, no...Chariot: How Alaska Escaped Nuclear Excavation." The Bulletin of the Atomic Scientists 45, no. 10 (1989): 28-37. Otway, Harry J., Dagmar Maurer, and

  6. An Interview with David Florio.

    ERIC Educational Resources Information Center

    Educational Evaluation and Policy Analysis, 1981

    1981-01-01

    American Educational Research Association's (AERA) lobbyist in Washington promotes educational research as a positive resource for educators. He acts to influence governmental policies which affect research. AERA represents a diversified membership by supporting a broad portfolio of government investments in educational research. AERA never takes…

  7. 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…

  8. 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.…

  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. 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…

  11. 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…

  12. 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.

  13. 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 Gandhi…

  14. A Case of You: Remembering David Fowler

    ERIC Educational Resources Information Center

    Pimm, David

    2004-01-01

    The author has framed this brief appreciation of David Flower in terms of influence; specifically, his influence as a teacher, both in person and through his writing (most of all his attempted rewriting of much of the history of Greek mathematics). The author will also make some second-order remarks about the influence of teachers.

  15. 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…

  16. 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…

  17. Speaking Personally--With Mark David Milliron

    ERIC Educational Resources Information Center

    American Journal of Distance Education, 2008

    2008-01-01

    This article presents an interview with Mark David Milliron, board chair of the Institute for the Study of Knowledge Management in Education, a trustee with Western Governors University, and a member of the advisory board for the University of Texas (UT) TeleCampus. He is also president and CEO of Catalyze Learning International, a private…

  18. Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

    PubMed Central

    Domingo-Domenech, J; Mellado, B; Ferrer, B; Truan, D; Codony-Servat, J; Sauleda, S; Alcover, J; Campo, E; Gascon, P; Rovira, A; Ross, J S; Fernández, P L; Albanell, J

    2005-01-01

    Nuclear factor (NF)-κB/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-κB/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-κB active state. Nuclear localisation of NF-κB was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-κB was detected in 57 (66.3%) specimens, and nuclear NF-κB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-κB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-κB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P=0.02), Gleason score (P=0.03) and nuclear NF-κB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-κB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-κB is an independent prognostic factor of biochemical relapse in prostate cancer. PMID:16278667

  19. 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.

  20. 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...

  1. David Gill: clock maker to global astronomer

    NASA Astrophysics Data System (ADS)

    Haley, P. A.

    2014-04-01

    Reduction in the uncertainty of physical measurements underpinned many advances in solar and stellar parallax, the determination of longitude, geodesy, and the accurate mapping of the heavens using celestial photography in the late nineteenth century. A pioneer in these areas, who successfully made the transition from clock maker in Aberdeen to H.M. Astronomer at the Cape of Good Hope was David Gill (1843-1914); Sir David Gill, K.C.B. from 1900. This paper celebrates the first third of Gill's career in astronomy and geodesy up to the time he was made redundant from Dun Echt Observatory at the end of 1875. It highlights how his horological skills were applied to telescope design and also how his aspirations to become a global astronomer started. The paper is timed to coincide with Gill's centenary anniversary year - he died 24 January 1914.

  2. Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma.

    PubMed

    Liu, Shuli; Shi, Lei; Yang, Xi; Ye, Dongxia; Wang, Tong; Dong, Cunshan; Guo, Wenzheng; Liao, Yueling; Song, Hongyong; Xu, Dongliang; Hu, Jingzhou; Zhang, Zhiyuan; Deng, Jiong

    2017-04-06

    Defects in apoptotic pathway contribute to development and progression of oral cancer. Survivin, a member of the inhibitors of apoptosis protein (IAP) family, is increased in many types of cancers. However, it is unclear whether increased survivin is associated with oral squamous cell carcinomas (OSCC), and what mechanisms may involve in. In this study, we examined survivin expression in OSCC compared to normal oral tissues via immunohistochemical staining. The results showed that, not only total survivin is increased in OSCCs, but also the subcellular location of survivin is changed in OSCCs compared to normal oral tissues. In most of normal oral tissues, survivin staining was either negative, or cytoplasmic positive/nuclear negative; whereas in most of OSCC tissues, survivin staining was nuclear positive. Statistic analysis indicates that nuclear survivin, rather than total or cytoplasmic one, correlates with tumor TNM stage and differentiation grade. Consistently, in vitro analysis showed that survivin is in cytoplasm in normal human oral kinotinocyte (HOK) cells; whereas it is in nucleus in OSCC HN6 cells. Importantly, treatment of HOK cells with HDAC inhibitor Trichostatin A (TSA) induces survivin acetylation and promotes its nuclear localization. Moreover, nuclear survivin in OSCC cells was acetylated at K129 in its C-terminal, suggesting that the acetylation is important for nuclear location of survivin. Our study demonstrates that it is nuclear survivin, rather than total or cytoplasmic one, associates with TNM stage and tumor grade of OSCC. Thus, we propose nuclear survivin as a prognostic marker for the progression of OSCC.

  3. 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.

  4. Nuclear Energy Policy

    DTIC Science & Technology

    2010-05-27

    small modular reactors and extend the lives and improve the operation of existing commercial nuclear power plants. 40 Interdisciplinary MIT Study, The Future of Nuclear Power, Massachusetts Institute of Technology, 2003, p. 79. 41 Gronlund, Lisbeth, David Lochbaum, and Edwin Lyman, Nuclear Power in a Warming World, Union of Concerned Scientists, December 2007. 42 Travis Madsen, Tony Dutzik, and Bernadette Del Chiaro, et al., Generating Failure: How Building Nuclear Power Plants

  5. 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.

  6. 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.

  7. 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.

  8. Kaposi's sarcoma-associated herpesvirus polyadenylated nuclear RNA: a structural scaffold for nuclear, cytoplasmic and viral proteins.

    PubMed

    Sztuba-Solinska, Joanna; Rausch, Jason W; Smith, Rodman; Miller, Jennifer T; Whitby, Denise; Le Grice, Stuart F J

    2017-04-05

    Kaposi's sarcoma-associated herpes virus (KSHV) polyadenylated nuclear (PAN) RNA facilitates lytic infection, modulating the cellular immune response by interacting with viral and cellular proteins and DNA. Although a number nucleoprotein interactions involving PAN have been implicated, our understanding of binding partners and PAN RNA binding motifs remains incomplete. Herein, we used SHAPE-mutational profiling (SHAPE-MaP) to probe PAN in its nuclear, cytoplasmic or viral environments or following cell/virion lysis and removal of proteins. We thus characterized and put into context discrete RNA structural elements, including the cis-acting Mta responsive element and expression and nuclear retention element (1,2). By comparing mutational profiles in different biological contexts, we identified sites on PAN either protected from chemical modification by protein binding or characterized by a loss of structure. While some protein binding sites were selectively localized, others were occupied in all three biological contexts. Individual binding sites of select KSHV gene products on PAN RNA were also identified in in vitro experiments. This work constitutes the most extensive structural characterization of a viral lncRNA and interactions with its protein partners in discrete biological contexts, providing a broad framework for understanding the roles of PAN RNA in KSHV infection.

  9. 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

  10. Reconstructing the Foreign Teacher: The Nativization of David Crook in Beijing

    ERIC Educational Resources Information Center

    Jacobsen, Craig K.

    2012-01-01

    This paper is a critical examination of the life and work of David Crook (1910-2000) as an English teacher in China from just prior to 1949 through the 1980's. It describes Crook's struggle to transcend attitudes of superiority commonly associated with native speaking English teachers at the time as well as his efforts to introduce innovations in…

  11. 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

  12. 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

  13. Nuclear γ-tubulin associates with nucleoli and interacts with tumor suppressor protein C53.

    PubMed

    Hořejší, Barbora; Vinopal, Stanislav; Sládková, Vladimíra; Dráberová, Eduarda; Sulimenko, Vadym; Sulimenko, Tetyana; Vosecká, Věra; Philimonenko, Anatoly; Hozák, Pavel; Katsetos, Christos D; Dráber, Pavel

    2012-01-01

    γ-Tubulin is assumed to be a typical cytosolic protein necessary for nucleation of microtubules from microtubule organizing centers. Using immunolocalization and cell fractionation techniques in combination with siRNAi and expression of FLAG-tagged constructs, we have obtained evidence that γ-tubulin is also present in nucleoli of mammalian interphase cells of diverse cellular origins. Immunoelectron microscopy has revealed γ-tubulin localization outside fibrillar centers where transcription of ribosomal DNA takes place. γ-Tubulin was associated with nucleolar remnants after nuclear envelope breakdown and could be translocated to nucleoli during mitosis. Pretreatment of cells with leptomycin B did not affect the distribution of nuclear γ-tubulin, making it unlikely that rapid active transport via nuclear pores participates in the transport of γ-tubulin into the nucleus. This finding was confirmed by heterokaryon assay and time-lapse imaging of photoconvertible protein Dendra2 tagged to γ-tubulin. Immunoprecipitation from nuclear extracts combined with mass spectrometry revealed an association of γ-tubulin with tumor suppressor protein C53 located at multiple subcellular compartments including nucleoli. The notion of an interaction between γ-tubulin and C53 was corroborated by pull-down and co-immunoprecipitation experiments. Overexpression of γ-tubulin antagonized the inhibitory effect of C53 on DNA damage G(2) /M checkpoint activation. The combined results indicate that aside from its known role in microtubule nucleation, γ-tubulin may also have nuclear-specific function(s).

  14. A-type Lamins Form Distinct Filamentous Networks with Differential Nuclear Pore Complex Associations.

    PubMed

    Xie, Wei; Chojnowski, Alexandre; Boudier, Thomas; Lim, John S Y; Ahmed, Sohail; Ser, Zheng; Stewart, Colin; Burke, Brian

    2016-10-10

    The nuclear lamina is a universal feature of metazoan nuclear envelopes (NEs) [1]. In mammalian cells, it appears as a 10-30 nm filamentous layer at the nuclear face of the inner nuclear membrane (INM) and is composed primarily of A- and B-type lamins, members of the intermediate filament family [2]. While providing structural integrity to the NE, the lamina also represents an important signaling and regulatory platform [3]. Two A-type lamin isoforms, lamins A and C (LaA and LaC), are expressed in most adult human cells. Encoded by a single gene, these proteins are largely identical, diverging only in their C-terminal tail domains. By contrast with that of LaC, the unique LaA tail undergoes extensive processing, including farnesylation and endo-proteolysis [4, 5]. However, functional differences between LaA and LaC are still unclear. Compounding this uncertainty, the structure of the lamina remains ill defined. In this study, we used BioID, an in vivo proximity-labeling method to identify differential interactors of A-type lamins [6]. One of these, Tpr, a nuclear pore complex (NPC) protein, is highlighted by its selective association with LaC. By employing superresolution microscopy, we demonstrate that this Tpr association is mirrored in enhanced interaction of LaC with NPCs. Further superresolution studies visualizing both endogenous A- and B-type lamins have allowed us to construct a nanometer-scale model of the mammalian nuclear lamina. Our data indicate that different A- and B-type lamin species assemble into separate filament networks that together form an extended composite structure at the nuclear periphery providing attachment sites for NPCs, thereby regulating their distribution.

  15. 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.

  16. David D. Derse, 1949-2009.

    PubMed

    Shuh, Maureen

    2009-12-01

    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.

  17. 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.

  18. The MUC1 Extracellular Domain Subunit Is Found in Nuclear Speckles and Associates with Spliceosomes

    PubMed Central

    Kumar, Priyadarsina; Ji, Jennifer W.; Martsching, Lindsay; Douglas, Gordon C.

    2012-01-01

    MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C) can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N) does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity ligation assay, subcellular fractionation, and immunoprecipitation suggests that MUC1-N is located in nuclear speckles (interchromatin granule clusters) and closely associates with the spliceosome protein U2AF65. Nuclear localization of MUC1-N was abolished when cells were treated with RNase A and nuclear localization was altered when cells were incubated with the transcription inhibitor 5,6-dichloro-1-b-d-ribofuranosylbenzimidazole (DRB). While MUC1-N predominantly associated with speckles, MUC1-C was present in the nuclear matrix, nucleoli, and the nuclear periphery. In some nuclei, confocal microscopic analysis suggest that MUC1-C staining is located close to, but only partially overlaps, MUC1-N in speckles. However, only MUC1-N was found in isolated speckles by Western blotting. Also, MUC1-C and MUC1-N distributed differently during mitosis. These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC1-C have

  19. 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.

  20. 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...

  1. 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…

  2. 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.

  3. 75 FR 10244 - Ellsworth, David C.; Notice of Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ... [Federal Register Volume 75, Number 43 (Friday, March 5, 2010)] [Notices] [Page 10244] [FR Doc No: 2010-4611] DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ID-3716-001] Ellsworth, David C.; Notice of Filing February 25, 2010. Take notice that on February 12, 2010, David C....

  4. 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.

  5. Self-association of Coilin Reveals a Common Theme in Nuclear Body Localization

    PubMed Central

    Hebert, Michael D.; Matera, A. Gregory

    2000-01-01

    We have found that coilin, the marker protein for Cajal bodies (coiled bodies, CBs), is a self-interacting protein, and we have mapped the domain responsible for this activity to the amino-terminus. Together with a nuclear localization signal, the self-interaction domain is necessary and sufficient for localization to CBs. Overexpression of various wild-type and mutant coilin constructs in HeLa cells results in disruption of both CBs and survival motor neurons (SMN) gems. Additionally, we have identified a cryptic nucleolar localization signal (NoLS), within the coilin protein, which may be exposed in specific coilin phospho-isoforms. The implications of these findings are discussed in light of the fact that other proteins known to localize within nuclear bodies (e.g., PML, SMN and Sam68) can also self-associate. Thus protein self-interaction appears to be a general feature of nuclear body marker proteins. PMID:11102515

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. Nuclear actin is partially associated with Cajal bodies in human cells in culture and relocates to the nuclear periphery after infection of cells by adenovirus 5.

    PubMed

    Gedge, L J E; Morrison, E E; Blair, G E; Walker, J H

    2005-02-15

    Cajal bodies are intra-nuclear structures enriched in proteins involved in transcription and mRNA processing. In this study, immunofluorescence microscopy experiments using a highly specific antibody to actin revealed nuclear actin spots that colocalized in part with p80 coilin-positive Cajal bodies. Actin remained associated with Cajal bodies in cells extracted to reveal the nuclear matrix. Adenovirus infection, which is known to disassemble Cajal bodies, resulted in loss of actin from these structures late in infection. In infected cells, nuclear actin was observed to relocate to structures at the periphery of the nucleus, inside the nuclear envelope. Based on these findings, it is suggested that actin may play an important role in the organization or function of the Cajal body.

  13. TECHNICAL BASIS FOR THE NUCLEAR CRITICALITY REPRESENTATIVE ACCIDENT & ASSOCIATED REPRESENTED HAZARDOUS CONDITIONS

    SciTech Connect

    GOETZ, T.G.

    2003-06-17

    This document was developed to support the documented safety analysis (DSA) and describes the process and basis for assigning risk bins for the nuclear criticality representative accident and associated hazardous conditions. Revision 1 incorporates ORP IRT comments to enhance the technical presentation and also makes editorial changes. This technical basis document was developed to support the documented safety analysis (DSA), and describes the risk binning process and the technical basis for assigning risk bins for the nuclear criticality representative accident and associated hazardous conditions. The purpose of the risk binning process is to determine the need for safety-significant structures, systems, and components (SSC) and technical safety requirement (TSR)-level controls for a given representative accident or represented hazardous condition based on an evaluation of the frequency and consequence.

  14. The JIM interview. David Korn, MD.

    PubMed

    Korn, D

    1995-04-01

    When David Korn, MD, was named dean of the Stanford University School of Medicine on October 9, 1984, he assumed leadership of a world class research institution. Stanford was at the forefront of medicine in the areas of transplantation and oncology, and the steady influx of privately insured patients had generated a net operating surplus of $17 million in that year alone. However, in the same issue of the Stanford University Hospital newsletter which announced the selection of Korn as Dean, a small article appeared on a new prospective payment system based on diagnosis-related groups (DRGs). The article stated that the new system had begun smoothly, though some payments for cost outliers had been delayed. Other cost containment measures soon followed, most notably the implementation of managed care, and by 1990, Stanford was $14 million in the red. Buffeted by changes in medical reimbursement, competition with less costly hospitals, and a nasty squabble with Congress over indirect research costs, Stanford has been on the frontlines of a struggle now confronting many academic medical centers. After successfully consolidating the university's clinical services into a unified Stanford Health System, Korn announced that he would be stepping down as Dean on April 1. Interviewed in his office in Palo Alto, Korn reflected on the difficulties of dealing with managed care, the current financial state of the institution, and what Stanford's experience may predict for other academic medical centers.

  15. Adenovirus DNA is associated with the nuclear matrix of infected cells.

    PubMed Central

    Younghusband, H B; Maundrell, K

    1982-01-01

    Viral DNA was found to be tightly associated with the nuclear matrix from HeLa cells lytically infected with human adenovirus type 5. The bound viral DNA, like cell DNA, was resistant to nonionic detergent and to extraction with high-salt (2 M NaCl) solution. However, whereas over 95% of the cell DNA was recovered in the matrix fraction, the amount of associated viral DNA varied during infection. Throughout the lytic cycle, the amount of matrix-associated adenovirus type 5 DNA increased until it reached a plateau level at 20 to 24 h after infection. At this stage, the matrix-bound DNA represented 87% of the total viral DNA; after this stage, additional newly synthesized viral DNA accumulated as non-matrix-associated DNA. DNase digestion studies revealed that all viral DNA sequences were equally represented in the matrix-bound DNA both early and late in infection; thus, unlike cell DNA, there seem to be no preferred attachment sites on the viral genome. An enrichment of viral DNA relative to cell DNA was found in the matrix-associated DNA after extensive DNase I digestion. This finding, together with an in situ hybridization study, suggests that the viral DNA is more intimately associated with the nuclear matrix than is cell DNA and probably does not exist in extended loops. Images PMID:6287038

  16. ELYS/MEL-28 chromatin association coordinates nuclear pore complex assembly and replication licensing.

    PubMed

    Gillespie, Peter J; Khoudoli, Guennadi A; Stewart, Graeme; Swedlow, Jason R; Blow, J Julian

    2007-10-09

    Xenopus egg extract supports all the major cell-cycle transitions in vitro. We have used a proteomics approach to identify proteins whose abundance on chromatin changes during the course of an in vitro cell cycle. One of the proteins we identified was ELYS/MEL-28, which has recently been described as the earliest-acting factor known to be required for nuclear pore complex (NPC) assembly [1-4]. ELYS interacts with the Nup107-160 complex and is required for its association with chromatin. ELYS contains an AT-hook domain, which we show binds to chromatin with a high affinity. This domain can compete with full-length ELYS for chromatin association, thereby blocking NPC assembly. This provides evidence that ELYS interacts directly with chromatin and that this interaction is essential for NPC assembly and compartmentalization of chromosomal DNA within the cell. Furthermore, we detected a physical association on chromatin between ELYS and the Mcm2-7 replication-licensing proteins. ELYS chromatin loading, NPC assembly, and nuclear growth were delayed when Mcm2-7 was prevented from loading onto chromatin. Because nuclear assembly is required to shut down licensing prior to entry into S phase, our results suggest a mechanism by which these two early cell-cycle events are coordinated with one another.

  17. The latency-associated nuclear antigen of Kaposi sarcoma–associated herpesvirus induces B cell hyperplasia and lymphoma

    PubMed Central

    Fakhari, Farnaz D.; Jeong, Joseph H.; Kanan, Yogita; Dittmer, Dirk P.

    2006-01-01

    Kaposi sarcoma–associated herpesvirus (KSHV) is a human lymphotropic herpesvirus. It is implicated in B cell neoplasias such as primary effusion lymphoma and multicentric Castleman disease in AIDS patients. The KSHV latency-associated nuclear antigen (LANA) is consistently expressed in all KSHV-associated tumor cells and was shown to bind the tumor suppressor proteins p53 and pRb. To test LANA’s contribution to lymphomagenesis in vivo we generated transgenic mice expressing LANA under the control of its own promoter, which is B cell specific. All of the transgenic mice developed splenic follicular hyperplasia due to an expansion of IgM+IgD+ B cells and showed increased germinal center formation. We also observed lymphomas, implying that LANA can activate B cells and provide the first step toward lymphomagenesis. PMID:16498502

  18. 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.

  19. A photographic diary of travels with David Kupfer.

    PubMed

    Estabrook, Ronald W

    2006-01-01

    The present article focuses on David Kupfer as a colleague and fellow traveler who participated in numerous meetings on cytochrome P450 held at exotic venues. It was always a pleasure to renew a long-standing friendship with David by meeting him at these meetings. His inscrutable smile combined with residues of an accent derived from his earlier background in Poland and Israel characterized this warm and delightful man. A number of photos of David in various locales are presented with this article in an attempt to fully capture the outstanding qualities of this man.

  20. Boundaries and interfaces in materials: The David A. Smith symposium

    SciTech Connect

    Pond, R.C. . Dept. of Materials Science and Engineering); Clark, W.A.T. . Dept. of Materials Science and Engineering); King, A.H. . Dept. of Materials Science and Engineering); Williams, D.B. (Lehigh Univ., Bethlehem, PA (United States

    1998-01-01

    Just over a year ago David Smith died. Then the loss of a distinguished scientist and dedicated teacher was mourned. Now it is time to celebrate his accomplishments both as a scientist and teacher and this book serves as a reminder of his many contributions to the field of boundaries and interfaces. Researchers from ten countries contributed their work to the symposium, many of whom were former students of David from his years in Oxford. This emphasizes David's tremendous effect on the career of many established scientists through his role as both a teacher and an advisor. Separate abstracts were prepared for 38 papers in this book.

  1. 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.

  2. 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.

  3. 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.

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

    PubMed

    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.

  5. 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.

  6. An Interview with Author/Screen Writer David Klass.

    ERIC Educational Resources Information Center

    Carroll, Sissi

    2002-01-01

    Presents an interview with Author/Screen Writer David Klass. Discusses his dual role as young adult author and Hollywood screenwriter. Illuminates important differences that Klass finds when working as writer of young adult books and as a screenwriter. (SG)

  7. 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

  8. 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

  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. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. David Simpson Receives 2012 Waldo E. Smith Medal: Citation

    NASA Astrophysics Data System (ADS)

    Lerner-Lam, Arthur

    2013-01-01

    David Simpson was awarded the 2012 Waldo E. Smith Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is for "extraordinary service to geophysics".

  17. David Haussler, Ph.D., Lectures on Cancer Genomics - TCGA

    Cancer.gov

    In this lecture, Dr. David Haussler provides a historical overview of the field of genomics leading up to TCGA, including the Cancer Genomics Hub at the University of California, Santa Cruz, and the TCGA Pan-Cancer initiative.

  18. 2. David Ames, Photographer, October 1982 VIEW EAST SHOWING WEST ...

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

    2. David Ames, Photographer, October 1982 VIEW EAST SHOWING WEST (FRONT) ELEVATION - Jacob Dingee House, 105 East Seventh Street (moved to 500 Block North Market Street), Wilmington, New Castle County, DE

  19. 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

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

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

    20. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR EAST WING LOOKING SOUTHWEST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

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

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

    10. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE OF EAST WING - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  2. 13. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    13. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH CENTRAL ENTRANCE/BREEZEWAY - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  3. 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 SOUTH FACADE OF WEST WING - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  4. 18. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    18. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR EAST WING LOOKING NORTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  5. 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 LOOKING NORTHEAST TO BREEZEWAY BETWEEN BARN AND MILKHOUSE - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  6. 7. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    7. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH FACADE CENTRAL DOORS - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  7. 14. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    14. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR WEST WING LOOKING NORTHEAST - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

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

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

    1. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH ELEVATION OF CENTRAL PORTION, CLOSER - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  9. 24. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    24. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR LOOKING EAST-SOUTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  10. 5. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    5. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH FACADE OF WEST WING FROM EAST NORTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

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

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

    2. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE WITH MANURE PIT IN FOREGROUND - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

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

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

    9. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH AND EAST FACADES OF EAST WING - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  13. 21. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    21. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR EAST WING LOOKING SOUTH - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  14. 22. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    22. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR CENTRAL STAIR LANDING LOOKING NORTH - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  15. 5. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    5. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 SOUTH FACADE OF CENTRAL PORTION, OBLIQUE VIEW - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

  16. 6. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    6. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH FACADE OF WEST WING FROM NORTHEAST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  17. 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

  18. 25. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    25. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR EAST ROOM LOOKING TO SOUTHWEST CORNER - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  19. 9. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    9. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 EAST FACADE, PART OF NORTH FACADE, TAKEN FROM NORTHWEST - Longview Farm, North Dairy Barn, Longview Road, Lees Summit, Jackson County, MO

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

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

    19. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR FIRST FLOOR EAST WING LOOKING NORTH - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

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

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

    2. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 NORTH ELEVATION OF CENTRAL PORTION - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  2. 23. Historic American Buildings Survey David J. Kaminsky, Photographer August ...

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

    23. Historic American Buildings Survey David J. Kaminsky, Photographer August 1978 INTERIOR SECOND FLOOR CENTRAL ROOM LOOKING WEST - Longview Farm, South Dairy Barn-Milkhouse, Longview Road, Lees Summit, Jackson County, MO

  3. 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)

  4. Downregulation of Iduna is associated with AIF nuclear translocation in neonatal brain after hypoxia-ischemia.

    PubMed

    Yang, Xiaoxia; Cheng, Jianhua; Gao, Yubo; Ding, Juan; Ni, Xinli

    2017-03-27

    In adult stroke models, the neuroprotective protein, Iduna, inhibits poly (ADP-ribose) polymerase-1 (PARP-1)-dependent cell death by decreasing apoptosis-inducing factor (AIF) nuclear translocation. Because the PARP1-dependent pathway and Iduna, which promotes AIF degradation, contribute to hypoxic-ischemic (HI) brain damage in the immature brain, we examined the relationship between Iduna expression and AIF nuclear translocation in the cerebral cortex of postnatal day 7 rats after HI. Ninety rats were divided into three groups: sham, 1-h hypoxia and 2-h hypoxia. The HI insult was induced by permanent ligation of the left common carotid artery plus 1 or 2h of hypoxia. Brain damage pathological features were evaluated by hematoxylin and eosin staining, Nissl staining, transmission electron microscopy, TUNEL staining and immunofluorescence. Immunohistochemistry and western blot analysis were used to assess protein expression and ubiquitination status of AIF. The interaction between Iduna and AIF was tested by co-immunoprecipitation. Learning and memory were analyzed by the Morris water maze test. Compared with sham animals, the number of surviving neurons in the cerebral cortex decreased, and cell damage and DNA breakage were severe in rats with HI, with worse damage in the 2-h group. Iduna expression significantly decreased, whereas nuclear AIF expression increased. Furthermore, Iduna downregulation negatively correlated with nuclear AIF abundance in the 2-h HI group (r=-0.950; P<0.0001). Additionally, learning and memory ability decreased with hypoxic time. These results suggest that AIF nuclear translocation and neuronal cell death are associated with Iduna loss after severe HI in the immature brain.

  5. 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.

  6. Ribosomal Protein S6 Interacts with the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus ▿

    PubMed Central

    Chen, Wuguo; Dittmer, Dirk P.

    2011-01-01

    The latency-associated nuclear antigen (LANA) is central to the maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) and to the survival of KSHV-carrying tumor cells. In an effort to identify interaction partners of LANA, we purified authentic high-molecular-weight complexes of LANA by conventional chromatography followed by immunoprecipitation from the BC-3 cell line. This is the first analysis of LANA-interacting partners that is not based on forced ectopic expression of LANA. Subsequent tandem mass spectrometry (MS/MS) analysis identified many of the known LANA-interacting proteins. We confirmed LANA's interactions with histones. Three classes of proteins survived our stringent four-step purification procedure (size, heparin, anion, and immunoaffinity chromatography): two heat shock proteins (Hsp70 and Hsp96 precursor), signal recognition particle 72 (SRP72), and 10 different ribosomal proteins. These proteins are likely involved in structural interactions within LANA high-molecular-weight complexes. Here, we show that ribosomal protein S6 (RPS6) interacts with LANA. This interaction is mediated by the N-terminal domain of LANA and does not require DNA or RNA. Depletion of RPS6 from primary effusion lymphoma (PEL) cells dramatically decreases the half-life of full-length LANA. The fact that RPS6 has a well-established nuclear function beyond its role in ribosome assembly suggests that RPS6 (and by extension other ribosomal proteins) contributes to the extraordinary stability of LANA. PMID:21734034

  7. 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.

  8. 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

  9. 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

  10. Identifying Novel Transcriptional and Epigenetic Features of Nuclear Lamina-associated Genes.

    PubMed

    Wu, Feinan; Yao, Jie

    2017-12-01

    Because a large portion of the mammalian genome is associated with the nuclear lamina (NL), it is interesting to study how native genes resided there are transcribed and regulated. In this study, we report unique transcriptional and epigenetic features of nearly 3,500 NL-associated genes (NL genes). Promoter regions of active NL genes are often excluded from NL-association, suggesting that NL-promoter interactions may repress transcription. Active NL genes with higher RNA polymerase II (Pol II) recruitment levels tend to display Pol II promoter-proximal pausing, while Pol II recruitment and Pol II pausing are not correlated among non-NL genes. At the genome-wide scale, NL-association and H3K27me3 distinguishes two large gene classes with low transcriptional activities. Notably, NL-association is anti-correlated with both transcription and active histone mark levels among genes not significantly enriched with H3K9me3 or H3K27me3, suggesting that NL-association may represent a novel gene repression pathway. Interestingly, an NL gene subgroup is not significantly enriched with H3K9me3 or H3K27me3 and is transcribed at higher levels than the rest of NL genes. Furthermore, we identified distal enhancers associated with active NL genes and reported their epigenetic features.

  11. David Hartley's psychobiological associationism and the legacy of Aristotle.

    PubMed

    Buckingham, H W; Finger, S

    1997-04-01

    The idea that there are certain "laws" of learning (similarity, contrast, contiguity) can be traced to Aristotle. He maintained that external stimuli cause small movements in the vessels to the dominant heart, the vestiges of which can be linked to one another. Aristotle's laws of learning were incorporated into the writings of Hobbes, Locke, and Berkeley, men who said nothing about the physiological correlates of mental associations. This left the door open for David Hartley to combine mental associationism with the Newtonian idea that sensations can cause minute particle vibrations in the nerves. Hartley's amalgam of psychology, philosophy, and neurology was first presented in 1746, as a "trial balloon" at the end a little-known monograph on a treatment for kidney stones. It was repeated three years later in his better-known Observations on Man. In many ways, modern psychobiological connectionism can be traced back to Hartley's Conjectures of 1746, in which Aristotle's original thoughts were modified with then current ideas about functions of the mind and the nervous system.

  12. 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

  13. Nucleophosmin/B23 is a proliferate shuttle protein associated with nuclear matrix.

    PubMed

    Yun, Jing-Ping; Chew, Eng Ching; Liew, Choong-Tsek; Chan, John Y H; Jin, Mei-Lin; Ding, Ming-Xiao; Fai, Yam Hin; Li, H K Richard; Liang, Xiao-Man; Wu, Qiu-Liang

    2003-12-15

    It has become obvious that a better understanding and potential elucidation of the nucleolar phosphoprotein B23 involving in functional interrelationship between nuclear organization and gene expression. In present study, protein B23 expression were investigated in the regenerative hepatocytes at different periods (at days 0, 1, 2, 3, 4, 7) during liver regeneration after partial hepatectomy on the rats with immunohistochemistry and Western blot analysis. Another experiment was done with immunolabeling methods and two-dimensional (2-D) gel electrophoresis for identification of B23 in the regenerating hepatocytes and HepG2 cells (hepatoblastoma cell line) after sequential extraction with detergents, nuclease, and salt. The results showed that its expression in the hepatocytes had a locative move and quantitative change during the process of liver regeneration post-operation. Its immunochemical localization in the hepatocytes during the process showed that it moved from nucleoli of the hepatocytes in the stationary stage to nucleoplasm, cytoplasm, mitotic spindles, and mitotic chromosomes of the hepatocytes in the regenerating livers. It was quantitatively increased progressively to peak level at day 3 post-operation and declined gradually to normal level at day 7. It was detected in nuclear matrix protein (NMP) composition extracted from the regenerating hepatocytes and HepG2 cells and identified with isoelectric point (pI) value of 5.1 and molecular weight of 40 kDa. These results indicated that B23 was a proliferate shuttle protein involving in cell cycle and cell proliferation associated with nuclear matrix.

  14. 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.

  15. Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence.

    PubMed

    Smith, Carolyn L; Migliaccio, Ilenia; Chaubal, Vaishali; Wu, Meng-Fen; Pace, Margaret C; Hartmaier, Ryan; Jiang, Shiming; Edwards, Dean P; Gutiérrez, M Carolina; Hilsenbeck, Susan G; Oesterreich, Steffi

    2012-11-01

    Silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), also known as nuclear corepressor 2 (NCOR2) is a transcriptional corepressor for multiple members of the nuclear receptor superfamily of transcription factors, including estrogen receptor-α (ERα). In the classical model of corepressor action, SMRT binds to antiestrogen-bound ERα at target promoters and represses ERα transcriptional activity and gene expression. Herein SMRT mRNA and protein expression was examined in a panel of 30 breast cancer cell lines. Expression of both parameters was found to vary considerably amongst lines and the correlation between protein and mRNA expression was very poor (R (2) = 0.0775). Therefore, SMRT protein levels were examined by immunohistochemical staining of a tissue microarray of 866 patients with stage I-II breast cancer. Nuclear and cytoplasmic SMRT were scored separately according to the Allred score. The majority of tumors (67 %) were negative for cytoplasmic SMRT, which when detected was found at very low levels. In contrast, nuclear SMRT was broadly detected. There was no significant difference in time to recurrence (TTR) according to SMRT expression levels in the ERα-positive tamoxifen-treated patients (P = 0.297) but the difference was significant in the untreated patients (P = 0.01). In multivariate analysis, ERα-positive tamoxifen-untreated patients with high nuclear SMRT expression (SMRT 5-8, i.e., 2nd to 4th quartile) had a shorter TTR (HR = 1.94, 95 % CI, 1.24-3.04; P = 0.004) while there was no association with SMRT expression for ERα-positive tamoxifen-treated patients. There was no association between SMRT expression and overall survival for patients, regardless of whether they received tamoxifen. Thus while SMRT protein expression was not predictive of outcome after antiestrogen therapy, it may have value in predicting tumor recurrence in patients not receiving adjuvant tamoxifen therapy.

  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 Melcher: Award for Distinguished Scientific Early Career Contributions to Psychology.

    PubMed

    2011-11-01

    Presents David Melcher, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For his elegant and groundbreaking work on one of the most important problems in perceptual psychology, the transfer of perceptual representations across eye movements. David Melcher's innovative experiments used perceptual aftereffects to show how remapping of visual locations underlies the creation of the percept of a clear and stable world. His work on the accumulation of memory contributed importantly to the understanding of natural perceptual representations and their neural underpinnings. His elegant reviews of transsaccadic perception communicated to a broad audience the remarkable capacity of the brain to create seamless perceptual representations despite the disruptions produced by eye movements." (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  18. 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

  19. Anhydrobiosis-associated nuclear DNA damage and repair in the sleeping chironomid: linkage with radioresistance.

    PubMed

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

    2010-11-16

    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 ((4)He). 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

  20. Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status.

    PubMed

    Kumar, Bhavna; Yadav, Arti; Brown, Nicole V; Zhao, Songzhu; Cipolla, Michael J; Wakely, Paul E; Schmitt, Alessandra C; Baiocchi, Robert A; Teknos, Theodoros N; Old, Matthew; Kumar, Pawan

    2017-01-17

    Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. Our results show that nuclear PRMT5 was associated with poor overall survival (p < 0.012) and these patients had 1.732 times higher hazard of death (95% CI: 1.127-2.661) as compared to patients in whom PRMT5 was not present in the nucleus of the tumors. Nuclear PRMT5 expression was inversely correlated with p16-status (p < 0.001) and was significantly higher in tumor samples from patients who smoked > 10 pack-years (p = 0.013). In addition, nuclear PRMT5 was directly correlated with cyclin D1 (p = 0.0101) and IL-6 expression (p < 0.001). In a subgroup survival analysis, nuclear PRMT5-positive/IL-6-positive group had worst survival, whereas nuclear PRMT5-negative/IL-6-negative group had the best survival. Similarly, patients with p16-negative/nuclear PRMT5-positive tumors had worse survival compared to patients with p16-positive/nuclear PRMT5-negative tumors. Our mechanistic results suggest that IL-6 promotes nuclear translocation of PRMT5. Taken together, our results demonstrate for the first time that nuclear PRMT5 expression is associated with poor clinical outcome in OPSCC patients and IL-6 plays a role in the nuclear translocation of PRMT5.

  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. Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus.

    PubMed

    Jeong, Joseph H; Orvis, Joshua; Kim, Jong Wook; McMurtrey, Curtis P; Renne, Rolf; Dittmer, Dirk P

    2004-04-16

    Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 has been established as the etiological agent of Kaposi's sarcoma and certain AIDS-associated lymphomas. KSHV establishes latent infection in these tumors, invariably expressing high levels of the viral latency-associated nuclear antigen (LANA) protein. LANA is necessary and sufficient to maintain the KSHV episome. It also modulates viral and cellular transcription and has been implicated directly in oncogenesis because of its ability to bind to the p53 and pRb tumor suppressor proteins. Previously, we identified the LANA promoter (LANAp) and showed that it was positively regulated by LANA itself. Here, we present a detailed mutational analysis and define cis-acting elements and trans-acting factors for the core LANAp. We found that a downstream promoter element, TATA box, and GC box/Sp1 site at -29 are all individually required for activity. This architecture places LANAp into the small and unusual group of eukaryotic promoters that contain both the downstream promoter element and TATA element but lack a defined initiation site. Furthermore, we demonstrate that LANA regulates its own promoter via its C-terminal domain and does bind to a defined site within the core promoter.

  3. Self-association of cromolyn sodium in aqueous solution characterized by nuclear magnetic resonance spectroscopy.

    PubMed

    Ding, Xuan; Stringfellow, Thomas C; Robinson, Joseph R

    2004-05-01

    The major objective of this study was to investigate and characterize the solution properties of cromolyn sodium (in D(2)O or D(2)O/H(2)O phosphate buffer at pH 7.5) using nuclear magnetic resonance (NMR) spectroscopy. The self-association of cromolyn molecules was examined primarily via one-dimensional (1)H and (13)C, and two-dimensional homonuclear NOESY NMR. Significant spectral shifts were observed for a majority of cromolyn (1)H and (13)C resonances, and are attributed to inter-molecular ring-stacking association accompanied by intra-molecular conformational changes. The critical self-association concentration was determined to be 10 mg/mL at pH 7.5 and 25 degrees C by measuring the chemical shift of a specific cromolyn (1)H resonance. The observed magnitude and sign changes of NOESY correlations indicate the formation of cromolyn aggregates with restricted molecular mobility. Mesomorphic liquid crystal formation is suggested by uniformly pronounced line broadening in concentrated cromolyn solutions; the transition concentration was approximately 60 mg/mL at 25 degrees C, which is consistent with literature findings based on other techniques. A stronger tendency toward association was observed at lower temperature but aggregation appeared to be independent of pH. Lastly, it was concluded that self-association of cromolyn is promoted by the presence of monovalent cations as a result of reduced electrostatic repulsive forces.

  4. Association of Nuclear Localization of a Long Interspersed Nuclear Element-1 Protein in Breast Tumors with Poor Prognostic Outcomes

    PubMed Central

    Harris, Chris R.; Normart, Robin; Yang, Qifeng; Stevenson, Elizabeth; Haffty, Bruce G.; Ganesan, Shridar; Cordon-Cardo, Carlos; Levine, Arnold J.; Tang, Laura H.

    2010-01-01

    Within healthy human somatic cells, retrotransposition by long interspersed nuclear element-1 (also known as LINE-1 or L1) is thought to be held in check by a variety of mechanisms, including DNA methylation and RNAi. The expression of L1-ORF1 protein, which is rarely found in normal tissue, was assayed using antibodies with a variety of clinical cancer specimens and cancer cell lines. L1-ORF1p expression was detected in nearly all breast tumors that the authors examined, and the protein was also present in a high percentage of ileal carcinoids, bladder, and pancreatic neuroendocrine tumors, as well as in a smaller percentage of prostate and colorectal tumors. Tumors generally demonstrated cytoplasmic L1-ORF1p; however, in several breast cancers, L1-ORF1p was nuclear. Patients with breast tumors displaying nuclear L1-ORF1p had a greater incidence of both local recurrence and distal metastases and also showed poorer overall survival when compared with patients with tumors displaying cytoplasmic L1-ORF1p. These data suggest that expression of L1-ORF1p is widespread in many cancers and that redistribution from cytoplasm to nucleus could be a poor prognostic indicator during breast cancer. High expression and nuclear localization of L1-ORF1p may result in a higher rate of L1 retrotransposition, which could increase genomic instability. PMID:20948976

  5. 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:…

  6. Genetic analysis of Père David's x red deer interspecies hybrids.

    PubMed

    Tate, M L; Goosen, G J; Patene, H; Pearse, A J; McEwan, K M; Fennessy, P F

    1997-01-01

    Interspecies hybrids provide unique opportunities for fundamental genetic analyses and for genetic improvement of farmed deer. We have bred F1 hybrids by artificial insemination of red deer hinds (Cervus elaphus) with semen from Père David's deer (Elaphurus davidianus). The male and female F1 Père David deer x red deer hybrids were fertile and in matings with red deer have produced over 300 viable backcross hybrids. DNA was collected from the backcross progeny as an international reference panel for gene linkage mapping and to investigate associations between segregating species-specific genetic markers and phenotypic traits. We have measured a range of phenotypic traits in the backcross hybrids and red deer. Several traits appear suitable for genetic analysis using mapped genetic markers, including gestation length, growth rate, live weight, head morphometrics, and tail length. Typically these traits show a large difference between Père David's deer and red deer and a high variance in the backcross so that many individuals have a phenotype outside the range observed in red deer.

  7. Mental disorder that afflicted King David the Great.

    PubMed

    Ben-Noun, Liubov

    2004-12-01

    This research uses the tools of modern medical science to study ancient descriptions of the symptoms suffered by King David. Biblical texts were examined, with a close study of verses relating to the mental disorder that afflicted King David, the second and greatest King of Israel, who ruled more than 3525 years ago. We include no commentaries, but refer only to the words of the Bible exactly as written. Evaluation of the passages referring to King David indicated that he was afflicted by some mental disorder, and among the many possibilities major depression, dysthymia and minor depression are the most likely. Of these diagnoses, major depression seems the most acceptable. This report suggests that the roots of contemporary psychiatry can be traced back to Biblical times.

  8. 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.

  9. A general nuclear magnetic resonance analysis of hetero-association of aromatic molecules in aqueous solution

    NASA Astrophysics Data System (ADS)

    Veselkov, Alexei N.; Evstigneev, Maxim P.; Veselkov, Dennis A.; Davies, David B.

    2001-08-01

    A general nuclear magnetic resonance analysis of a statistical-thermodynamical model of hetero-association of aromatic molecules in solution has been developed to take "edge effects" into consideration, i.e., the dependence of proton chemical shifts on the position of the molecule situated inside or at the edge of the aggregate. This generalized approach is compared with a previously published model, where an average contribution to proton shielding is considered irrespective of the position of the molecule in the stack. Association parameters have been determined from experimental concentration and temperature dependences of 500 MHz proton chemical shifts of the hetero-association of the acridine dye, proflavine, and the phenanthridinium dye, ethidium bromide, in aqueous solution. Differences in the parameters in the range 10%-30% calculated using the basic and generalized approaches have been found to depend substantially on the magnitude of the equilibrium hetero-association constant Khet—the larger the value of Khet, the higher the discrepancy between the two methods.

  10. 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

  11. Human GTPases associate with RNA polymerase II to mediate its nuclear import.

    PubMed

    Carré, Clément; Shiekhattar, Ramin

    2011-10-01

    Small GTPases share a biochemical mechanism and act as binary molecular switches. One important function of small GTPases in the cell is nucleocytoplasmic transport of both proteins and RNA. Here, we show the stable association of human GPN1 and GPN3, small GTPases related to Ran, with RNA polymerase II (RNAPII) isolated from either the cytoplasmic or nuclear fraction. GPN1 and GPN3 directly interact with RNAPII subunit 7 (RPB7)/RPB4 and the C-terminal domain (CTD) of RNAPII. Depletion of GPN1 or GPN3 using small interfering RNAs led to decreased RNAPII levels in the nucleus and an accumulation of this enzyme in the cytoplasm of human cells. Furthermore, isolation of a GPN1/GPN3/RNAPII complex from stable cell lines expressing a dominant negative GPN1 harboring mutations in the GTP-binding pocket demonstrated a role for these proteins in nuclear import of RNAPII. Thus, GPN1/GPN3 define a new family of small GTPases that are specialized for the transport of RNA polymerase II into the nucleus.

  12. The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression

    PubMed Central

    Schneider, Maren; Hellerschmied, Doris; Schubert, Tobias; Amlacher, Stefan; Vinayachandran, Vinesh; Reja, Rohit; Pugh, B. Franklin; Clausen, Tim; Köhler, Alwin

    2015-01-01

    Summary Nuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription, and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with the Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent at specific genes. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing. Our data provide mechanistic insight into how an NPC-associated adaptor complex accesses the core transcription machinery. PMID:26317468

  13. A horizontally transferred nuclear gene is associated with microhabitat variation in a natural plant population

    PubMed Central

    Tunlid, Anders; Ghatnekar, Lena

    2015-01-01

    Horizontal gene transfer involves the non-sexual interspecific transmission of genetic material. Even if they are initially functional, horizontally transferred genes are expected to deteriorate into non-expressed pseudogenes, unless they become adaptively relevant in the recipient organism. However, little is known about the distributions of natural transgenes within wild species or the adaptive significance of natural transgenes within wild populations. Here, we examine the distribution of a natural plant-to-plant nuclear transgene in relation to environmental variation within a wild population. Festuca ovina is polymorphic for an extra (second) expressed copy of the nuclear gene (PgiC) encoding cytosolic phosphoglucose isomerase, with the extra PgiC locus having been acquired horizontally from the distantly related grass genus Poa. We investigated variation at PgiC in samples of F. ovina from a fine-scale, repeating patchwork of grassland microhabitats, replicated within spatially separated sites. Even after accounting for spatial effects, the distributions of F. ovina individuals carrying the additional PgiC locus, and one of the enzyme products encoded by the locus, are significantly associated with fine-scale habitat variation. Our results suggest that the PgiC transgene contributes, together with the unlinked ‘native’ PgiC locus, to local adaptation to a fine-scale mosaic of edaphic and biotic grassland microhabitats. PMID:26674953

  14. Characterization of 3'----5' exonuclease associated with DNA polymerase of silkworm nuclear polyhedrosis virus.

    PubMed Central

    Mikhailov, V S; Marlyev, K A; Ataeva, J O; Kullyev, P K; Atrazhev, A M

    1986-01-01

    3'----5' Exonuclease specific for single-stranded DNA copurified with DNA polymerase of nuclear polyhedrosis virus of silkworm Bombyx mori (BmNPV Pol). BmNPV Pol has no detectable 5'----3' exonuclease activity on single-stranded or duplex DNA. Analysis of the products of 3'----5' exonucleolytic reaction showed that deoxynucleoside monophosphates were released during the hydrolysis of single-stranded DNA. The exonuclease activity cosedimented with the polymerase activity during ultracentrifugation of BmNPV Pol in glycerol gradient. The polymerase and the exonuclease activities of BmNPV Pol were inactivated by heat with nearly identical kinetics. The mode of the hydrolysis of single-stranded DNA by BmNPV Pol-associated exonuclease was strictly distributive. The enzyme dissociated from single-stranded DNA after the release of a single dNMP and then reassociated with a next polynucleotide being degradated. Images PMID:3012482

  15. 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

  16. Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients.

    PubMed

    Maciejczyk, Adam; Łacko, Aleksandra; Ekiert, Marcin; Jagoda, Ewa; Wysocka, Teresa; Matkowski, Rafał; Hałoń, Agnieszka; Györffy, Balázs; Lage, Hermann; Surowiak, Paweł

    2013-04-01

    S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.

  17. 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

  18. 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.

  19. Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data.

    PubMed

    Dudbridge, Frank

    2008-01-01

    Missing data occur in genetic association studies for several reasons including missing family members and uncertain haplotype phase. Maximum likelihood is a commonly used approach to accommodate missing data, but it can be difficult to apply to family-based association studies, because of possible loss of robustness to confounding by population stratification. Here a novel likelihood for nuclear families is proposed, in which distinct sets of association parameters are used to model the parental genotypes and the offspring genotypes. This approach is robust to population structure when the data are complete, and has only minor loss of robustness when there are missing data. It also allows a novel conditioning step that gives valid analysis for multiple offspring in the presence of linkage. Unrelated subjects are included by regarding them as the children of two missing parents. Simulations and theory indicate similar operating characteristics to TRANSMIT, but with no bias with missing data in the presence of linkage. In comparison with FBAT and PCPH, the proposed model is slightly less robust to population structure but has greater power to detect strong effects. In comparison to APL and MITDT, the model is more robust to stratification and can accommodate sibships of any size. The methods are implemented for binary and continuous traits in software, UNPHASED, available from the author.

  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. My Journey Into the Physics of David Finkelstein

    NASA Astrophysics Data System (ADS)

    Alexander, Stephon

    2017-01-01

    David Finkelstein was a co-pioneer of the use of topology and solitons in theoretical physics. The author reflects on the great impact Finkelstein had on his research throughout his career. The author provides an application of one of Finkelsteins idea pertaining to the fusion of quantum theory with relativity by utilizing techniques from Loop Quantum Gravity.

  2. Reflections on the Freshman Year: An Interview with David Riesman.

    ERIC Educational Resources Information Center

    Gardner, John N.; Barefoot, Betsy

    1991-01-01

    An interview with David Riesman, founder of Harvard University's (Massachusetts) freshman seminar program, covers the origins and structure of the seminars, Riesman's own college experience, the importance of the college experience, faculty research, and the role of faculty in student intellectual development. (MSE)

  3. 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…

  4. The Sociological Foundations of David Elliott's "Music Matters" Philosophy.

    ERIC Educational Resources Information Center

    Paul, Stephen J.

    2000-01-01

    Focuses on the ideas presented in the book, "Music Matters (David Elliott)." Discusses Elliott's stance on praxialism, stating that his book is based on social mediation of action as its behavioral theory. Addresses Elliott's concept of expertise and topics using an interactionist perspective as a means of interpretation. (CMK)

  5. 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)

  6. Astronaut David Scott practicing for Gemini 8 EVA

    NASA Technical Reports Server (NTRS)

    1966-01-01

    Astronaut David R. Scott practicing for Gemini 8 extravehicular acitivity (EVA) in bldg 4 of the Manned Spacecraft Center on the air bearing floor. He is wearing the the Hand-Held Maneuvering Unit which he will use during the EVA.

  7. David E. Smith Receives 2012 Charles A. Whitten Medal: Citation

    NASA Astrophysics Data System (ADS)

    Phillips, Roger J.

    2013-01-01

    David E. Smith was awarded the 2012 Charles A. Whitten Medal at the AGU Fall Meeting Honors Ceremony, held on 5 December 2012 in San Francisco, Calif. The medal is for "outstanding achievement in research on the form and dynamics of the Earth and planets."

  8. David P. McAllester on Navajo Music.

    ERIC Educational Resources Information Center

    Campbell, Patricia Shehan

    1994-01-01

    Asserts that music teachers increasingly are interested in music that originates outside the Western European tradition. Presents an interview with David P. McAllester on world music, the musical culture of the Navajo people, and how it should be taught in music classrooms. (CFR)

  9. "The Word I Would Use Is 'Aesthetic'": Reading David Hawkins.

    ERIC Educational Resources Information Center

    Featherstone, Helen; Featherstone, Joseph

    2002-01-01

    Discusses the life of David Hawkins, one of the most influential educators involved in school reform in the 1960s. Focuses on the aesthetic as the center of Hawkins' vision of schooling. Compares Hawkins' perspective to Dewey's in terms of the aesthetic. (KHR)

  10. Astronauts David Griggs and Jeff Hoffman in Egress training

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Astronaut David Griggs, wearing an extravehicular mobility unit (EMU), practices emergency egress from the space shuttle during an underwater test in the Weightless Environment Training Facility (WETF) (26473); Griggs (left) and Astronaut Jeff Hoffman train for egress in the WETF (26474).

  11. David Reeder and the History of Urban Education

    ERIC Educational Resources Information Center

    Marsden, Bill; Grosvenor, Ian

    2007-01-01

    David Reeder was one of the most important conservers of the traditions of urban history scholarship established during the 1960s at the University of Leicester under the leadership of Professor H. J. Dyos. Among Reeder's major achievements were the application of the skills and objectives of such scholarship to the history of education, and in…

  12. 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.

  13. 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.

  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. 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…

  16. 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)

  17. 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…

  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. 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.

  20. 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.

  1. 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.

  2. Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes

    SciTech Connect

    Rahayu, Retno; Ohsaki, Eriko; Omori, Hiroko; Ueda, Keiji

    2016-09-15

    In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super-resolution laser confocal microscopy and correlative fluorescence microscopy–electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. - Highlights: • This is the first report showing LANA dots on mitotic chromosomes by fluorescent microscopy followed by electron microscopy. • LANA dots localized randomly on condensed chromosomes other than centromere/pericentromere and telomere/peritelomre. • Cellular mitotic checkpoint should not be always involved in the segregation of KSHV genomes in the latency.

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

    PubMed

    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

    2015-11-24

    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.

  4. 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

  5. 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

  6. 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.

  7. Components of the Human SWI/SNF Complex Are Enriched in Active Chromatin and Are Associated with the Nuclear Matrix

    PubMed Central

    Reyes, Jose C.; Muchardt, Christian; Yaniv, Moshe

    1997-01-01

    Biochemical and genetic evidence suggest that the SWI/SNF complex is involved in the remodeling of chromatin during gene activation. We have used antibodies specific against three human subunits of this complex to study its subnuclear localization, as well as its potential association with active chromatin and the nuclear skeleton. Immunofluorescence studies revealed a punctate nuclear labeling pattern that was excluded from the nucleoli and from regions of condensed chromatin. Dual labeling failed to reveal significant colocalization of BRG1 or hBRM proteins with RNA polymerase II or with nuclear speckles involved in splicing. Chromatin fractionation experiments showed that both soluble and insoluble active chromatin are enriched in the hSWI/SNF proteins as compared with bulk chromatin. hSWI/SNF proteins were also found to be associated with the nuclear matrix or nuclear scaffold, suggesting that a fraction of the hSWI/SNF complex could be involved in the chromatin organization properties associated with matrix attachment regions. PMID:9128241

  8. Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation.

    PubMed

    Chen, Wei-Yen; Lin, Chia-Lung; Chuang, Jen-Hua; Chiu, Fu-Yu; Sun, Yun-Ya; Liang, Mei-Chih; Lin, Yenshou

    2017-01-20

    Mammalian target of rapamycin (mTOR) plays a range of crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, mTOR complex 1 and mTOR complex 2 (mTORC1 and mTORC2), via association with a series of different components; this allows the complexes to execute their wide range of functions. This study explores further the composition of the mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation and mass spectrometry, a novel Rictor associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified. The association between hnRNP M and Rictor was verified using recombinant and endogenous protein and the binding site was found to be within aa 1~532 of hnRNP M. The presence of hnRNP M significantly affects phosphorylation of SGK1 S422, but not of Akt S473, PKCα S657 and PKCζ T560. Furthermore, hnRNP M also plays a critical role in muscle differentiation because knock-down of either hnRNP M or Rictor in C2C12 myoblasts reduced differentiation. This decrease is able to be rescued by overexpression SGK S422D in hnRNP M knockdown C2C12 myoblasts. Taken together, we have identified a novel Rictor/mTOR binding molecule, hnRNP M, that allows mTORC2 signaling to phosphorylate SGK1 thus regulating muscle differentiation.

  9. Heterogeneous nuclear ribonucleoprotein M associates with mTORC2 and regulates muscle differentiation

    PubMed Central

    Chen, Wei-Yen; Lin, Chia-Lung; Chuang, Jen-Hua; Chiu, Fu-Yu; Sun, Yun-Ya; Liang, Mei-Chih; Lin, Yenshou

    2017-01-01

    Mammalian target of rapamycin (mTOR) plays a range of crucial roles in cell survival, growth, proliferation, metabolism, and morphology. However, mTOR forms two distinct complexes, mTOR complex 1 and mTOR complex 2 (mTORC1 and mTORC2), via association with a series of different components; this allows the complexes to execute their wide range of functions. This study explores further the composition of the mTORC2 complex. Utilizing Rictor knock-out cells, immunoprecipitation and mass spectrometry, a novel Rictor associated protein, heterogeneous nuclear ribonucleoprotein M (hnRNP M), was identified. The association between hnRNP M and Rictor was verified using recombinant and endogenous protein and the binding site was found to be within aa 1~532 of hnRNP M. The presence of hnRNP M significantly affects phosphorylation of SGK1 S422, but not of Akt S473, PKCα S657 and PKCζ T560. Furthermore, hnRNP M also plays a critical role in muscle differentiation because knock-down of either hnRNP M or Rictor in C2C12 myoblasts reduced differentiation. This decrease is able to be rescued by overexpression SGK S422D in hnRNP M knockdown C2C12 myoblasts. Taken together, we have identified a novel Rictor/mTOR binding molecule, hnRNP M, that allows mTORC2 signaling to phosphorylate SGK1 thus regulating muscle differentiation. PMID:28106162

  10. 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.

  11. 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.

  12. 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.

  13. 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'.

  14. 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.

  15. Breast Cancer–Associated Abraxas Mutation Disrupts Nuclear Localization and DNA Damage Response Functions

    PubMed Central

    Solyom, Szilvia; Aressy, Bernadette; Pylkäs, Katri; Patterson-Fortin, Jeffrey; Hartikainen, Jaana M.; Kallioniemi, Anne; Kauppila, Saila; Nikkilä, Jenni; Kosma, Veli-Matti; Mannermaa, Arto; Greenberg, Roger A.; Winqvist, Robert

    2013-01-01

    Breast cancer is the most common cancer in women in developed countries and has a well-established genetic component. Germline mutations in a network of genes encoding BRCA1, BRCA2, and their interacting partners confer hereditary susceptibility to breast cancer. Abraxas directly interacts with the BRCA1 BRCT (BRCA1 carboxyl-terminal) repeats and contributes to BRCA1-dependent DNA damage responses, making Abraxas a candidate for yet unexplained disease susceptibility. Here, we have screened 125 Northern Finnish breast cancer families for coding region and splice-site Abraxas mutations and genotyped three tagging single-nucleotide polymorphisms within the gene from 991 unselected breast cancer cases and 868 female controls for common cancer-associated variants. A novel heterozygous alteration, c.1082G>A (Arg361Gln), that results in abrogated nuclear localization and DNA response activities was identified in three breast cancer families and in one additional familial case from an unselected breast cancer cohort, but not in healthy controls (P = 0.002). On the basis of its exclusive occurrence in familial cancers, disease cosegregation, evolutionary conservation, and disruption of critical BRCA1 functions, the recurrent Abraxas c.1082G>A mutation connects to cancer predisposition. These findings contribute to the concept of a BRCA-centered tumor suppressor network and provide the identity of Abraxas as a new breast cancer susceptibility gene. PMID:22357538

  16. 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.

  17. Identification and Evaluation of Human Factors Issues Associated with Emerging Nuclear Plant Technology

    SciTech Connect

    O'Hara,J.M.; Higgins,J.; Brown, William S.

    2009-04-01

    This study has identified human performance research issues associated with the implementation of new technology in nuclear power plants (NPPs). To identify the research issues, current industry developments and trends were evaluated in the areas of reactor technology, instrumentation and control technology, human-system integration technology, and human factors engineering (HFE) methods and tools. The issues were prioritized into four categories based on evaluations provided by 14 independent subject matter experts representing vendors, utilities, research organizations and regulators. Twenty issues were categorized into the top priority category. The study also identifies the priority of each issue and the rationale for those in the top priority category. The top priority issues were then organized into research program areas of: New Concepts of Operation using Multi-agent Teams, Human-system Interface Design, Complexity Issues in Advanced Systems, Operating Experience of New and Modernized Plants, and HFE Methods and Tools. The results can serve as input to the development of a long-term strategy and plan for addressing human performance in these areas to support the safe operation of new NPPs.

  18. Small-molecule targeting of proliferating cell nuclear antigen chromatin association inhibits tumor cell growth.

    PubMed

    Tan, Zongqing; Wortman, Matthew; Dillehay, Kelsey L; Seibel, William L; Evelyn, Chris R; Smith, Shanna J; Malkas, Linda H; Zheng, Yi; Lu, Shan; Dong, Zhongyun

    2012-06-01

    Proliferating cell nuclear antigen (PCNA), a potential anticancer target, forms a homotrimer and is required for DNA replication and numerous other cellular processes. The purpose of this study was to identify novel small molecules that modulate PCNA activity to affect tumor cell proliferation. An in silico screen of a compound library against a crystal structure of PCNA and a subsequent structural similarity search of the ZINC chemical database were carried out to derive relevant docking partners. Nine compounds, termed PCNA inhibitors (PCNA-Is), were selected for further characterization. PCNA-I1 selectively bound to PCNA trimers with a dissociation constant (K(d)) of ~0.2 to 0.4 μM. PCNA-Is promoted the formation of SDS-refractory PCNA trimers. PCNA-I1 dose- and time-dependently reduced the chromatin-associated PCNA in cells. Consistent with its effects on PCNA trimer stabilization, PCNA-I1 inhibited the growth of tumor cells of various tissue types with an IC(50) of ~0.2 μM, whereas it affected the growth of nontransformed cells at significantly higher concentrations (IC(50), ~1.6 μM). Moreover, uptake of BrdU was dose-dependently reduced in cells treated with PCNA-I1. Mechanistically the PCNA-Is mimicked the effect of PCNA knockdown by siRNA, inducing cancer cell arrest at both the S and G(2)/M phases. Thus, we have identified a class of compounds that can directly bind to PCNA, stabilize PCNA trimers, reduce PCNA association with chromatin, and inhibit tumor cell growth by inducing a cell cycle arrest. They are valuable tools in studying PCNA function and may be useful for future PCNA-targeted cancer therapy.

  19. Evaluation of the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing.

    PubMed

    Ferrari, Robert

    2015-09-01

    The objective of this study was to evaluate the Canadian Rheumatology Association Choosing Wisely recommendation concerning anti-nuclear antibody (ANA) testing. Patients with joint pain/stiffness/swelling were assessed to determine if ANA testing was indicated. An a priori threshold was set before ANA testing would be considered. Those who did not have ANA testing ordered were followed for 1 year to determine if any of them went on to have a diagnosis of systemic lupus erythematosus (SLE) or other connective tissue disease. A parallel study was conducted with a similar a priori threshold for the use of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody testing in the diagnosis of rheumatoid arthritis (RA), and again, patients were followed for 1 year. A total of 866 subjects were examined, 509 females (58.8 %) and 357 males (41.2 %). The mean age of the group was 47.5 ± 16.8 years. The mean duration of symptoms was 12.0 ± 5.6 weeks. Of the 866 subjects, 68 met an a priori threshold for ordering ANA, RF, and anti-CCP testing. Of these 68, there was a newly diagnosed case of SLE, 4 newly diagnosed cases of RA, and 3 cases of polymyalgia rheumatica. The remaining 798 subjects were followed for approximately 1 year and none developed evidence of SLE, RA, or other connective tissue disease. In the evaluation of non-specific musculoskeletal symptoms, setting an a priori threshold for ordering serology in keeping with the spirit of the Canadian Rheumatology Association Choosing Wisely recommendation for antibody testing results in a very low risk of missing a case of systemic lupus erythematosus or rheumatoid arthritis.

  20. 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.

  1. 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.

  2. About David Ruelle, After His 80th Birthday

    NASA Astrophysics Data System (ADS)

    Gallavotti, Giovanni

    2017-02-01

    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.

  3. Digital Anthropometric Video-Imaging Device (DAVID) Operational Manual

    DTIC Science & Technology

    2002-08-29

    wish to thank John Joseph ofIsoperformance, Inc., for developing the initial Visual Basic program for the DAVID and the staff of SPA WAR System Center...operator in demographic data field of Remote Program 3. DIMENSIONNAME: Name of dimension in Microsoft Visual Basic program 4. SHORTNAME: Abbreviation for...measurement (e.g., SH, HT, etc.) in Microsoft Visual Basic program 5. ISCALIB: Switch in Microsoft Visual Basic program to indicate if measurement is

  4. 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. |

  5. Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (KSHV) upregulates survivin expression in KSHV-Associated B-lymphoma cells and contributes to their proliferation.

    PubMed

    Lu, Jie; Verma, Subhash C; Murakami, Masanao; Cai, Qiliang; Kumar, Pankaj; Xiao, Bingyi; Robertson, Erle S

    2009-07-01

    Survivin is a master regulator of cell proliferation and cell viability and is highly expressed in most human tumors. The molecular network linked to survivin expression in tumors has not been completely elucidated. In this study, we show that latency-associated nuclear antigen (LANA), a multifunctional protein of Kaposi's sarcoma-associated herpesvirus (KSHV) that is found in Kaposi's sarcoma tumors, upregulates survivin expression and increases the proliferation of KSHV-infected B cells. Analysis of pathway-specific gene arrays showed that survivin expression was highly upregulated in BJAB cells expressing LANA. The mRNA levels of survivin were also upregulated in HEK 293 and BJAB cells expressing LANA. Similarly, protein levels of survivin were significantly higher in LANA-expressing, as well as KSHV-infected, cells. Survivin promoter activity assays identified GC/Sp1 and p53 cis-acting elements within the core promoter region as being important for LANA activity. Gel mobility shift assays revealed that LANA forms a complex with Sp1 or Sp1-like proteins bound to the GC/Sp1 box of the survivin promoter. In addition, a LANA/p53 complex bound to the p53 cis-acting element within the survivin promoter, indicating that upregulation of survivin expression can also occur through suppression of p53 function. Furthermore, immunohistochemistry analyses revealed that survivin expression was upregulated in KSHV-associated Kaposi's sarcoma tissue, suggesting that LANA plays an important role in the upregulation of survivin expression in KSHV-infected endothelial cells. Knockdown of survivin expression by lentivirus-delivered small hairpin RNA resulted in loss of cell proliferation in KSHV-infected cells. Therefore, upregulation of survivin expression in KSHV-associated human cells contributes to their proliferation.

  6. Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function

    PubMed Central

    2011-01-01

    Background Central to the fully competent replication cycle of the human immunodeficiency virus type 1 (HIV-1) is the nuclear export of unspliced and partially spliced RNAs mediated by the Rev posttranscriptional activator and the Rev response element (RRE). Results Here, we introduce a novel method to explore the proteome associated with the nuclear HIV-1 RNAs. At the core of the method is the generation of cell lines harboring an integrated provirus carrying RNA binding sites for the MS2 bacteriophage protein. Flag-tagged MS2 is then used for affinity purification of the viral RNA. By this approach we found that the viral RNA is associated with the host nuclear matrix component MATR3 (Matrin 3) and that its modulation affected Rev activity. Knockdown of MATR3 suppressed Rev/RRE function in the export of unspliced HIV-1 RNAs. However, MATR3 was able to associate with Rev only through the presence of RRE-containing viral RNA. Conclusions In this work, we exploited a novel proteomic method to identify MATR3 as a cellular cofactor of Rev activity. MATR3 binds viral RNA and is required for the Rev/RRE mediated nuclear export of unspliced HIV-1 RNAs. PMID:21771346

  7. Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix- associated PML bodies

    PubMed Central

    1995-01-01

    The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells due to the expression of the PML-RAR alpha hybrid. Here we report that adenovirus infection causes a drastic redistribution of PML from spherical nuclear bodies into fibrous structures. The product encoded by adenovirus E4- ORF3 is shown to be responsible for this reorganization and to colocalize with PML into these fibers. In addition, we demonstrate that E1A oncoproteins concentrate in the PML domains, both in infected and transiently transfected cells, and that this association requires the conserved amino acid motif (D)LXCXE, common to all viral oncoproteins that bind pRB or the related p107 and p130 proteins. The SV-40 large T antigen, another member of this oncoprotein family is also found in close association with the PML nuclear bodies. Taken together, the present data indicate that the subnuclear domains containing PML represent a preferential target for DNA tumor viruses, and therefore suggest a more general involvement of the PML nuclear bodies in oncogenic processes. PMID:7559785

  8. 75 FR 77920 - Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 2 and 3; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ..., Contact: Mr. Andrew Stuyvenberg, Projects Branch 2, Division of License Renewal, Office of Nuclear Reactor... Commission. David J. Wrona, Chief, Projects Branch 2, Division of License Renewal, Office of Nuclear Reactor... From the Federal Register Online via the Government Publishing Office NUCLEAR...

  9. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects.

    PubMed

    Hashizume, Osamu; Ohnishi, Sakiko; Mito, Takayuki; Shimizu, Akinori; Ishikawa, Kaori; Iashikawa, Kaori; Nakada, Kazuto; Soda, Manabu; Mano, Hiroyuki; Togayachi, Sumie; Miyoshi, Hiroyuki; Okita, Keisuke; Hayashi, Jun-Ichi

    2015-05-22

    Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. We carried out reprogramming of human fibroblast lines derived from elderly subjects by generating their induced pluripotent stem cells (iPSCs), and examined another possibility, namely that these aging phenotypes are controlled not by mutations but by epigenetic regulation. Here, we show that reprogramming of elderly fibroblasts restores age-associated mitochondrial respiration defects, indicating that these aging phenotypes are reversible and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either the nuclear or the mitochondrial genome. Microarray screening revealed that epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes.

  10. Epigenetic regulation of the nuclear-coded GCAT and SHMT2 genes confers human age-associated mitochondrial respiration defects

    PubMed Central

    Hashizume, Osamu; Ohnishi, Sakiko; Mito, Takayuki; Shimizu, Akinori; Ishikawa, Kaori; Nakada, Kazuto; Soda, Manabu; Mano, Hiroyuki; Togayachi, Sumie; Miyoshi, Hiroyuki; Okita, Keisuke; Hayashi, Jun-Ichi

    2015-01-01

    Age-associated accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed to be responsible for the age-associated mitochondrial respiration defects found in elderly human subjects. We carried out reprogramming of human fibroblast lines derived from elderly subjects by generating their induced pluripotent stem cells (iPSCs), and examined another possibility, namely that these aging phenotypes are controlled not by mutations but by epigenetic regulation. Here, we show that reprogramming of elderly fibroblasts restores age-associated mitochondrial respiration defects, indicating that these aging phenotypes are reversible and are similar to differentiation phenotypes in that both are controlled by epigenetic regulation, not by mutations in either the nuclear or the mitochondrial genome. Microarray screening revealed that epigenetic downregulation of the nuclear-coded GCAT gene, which is involved in glycine production in mitochondria, is partly responsible for these aging phenotypes. Treatment of elderly fibroblasts with glycine effectively prevented the expression of these aging phenotypes. PMID:26000717

  11. 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.

  12. Magnesium Presence Prevents Removal of Antigenic Nuclear-Associated Proteins from Bovine Pericardium for Heart Valve Engineering.

    PubMed

    Dalgliesh, Ailsa J; Liu, Zhi Zhao; Griffiths, Leigh G

    2017-03-10

    Current heart valve prostheses are associated with significant complications, including aggressive immune response, limited valve life expectancy, and inability to grow in juvenile patients. Animal derived "tissue" valves undergo glutaraldehyde fixation to mask tissue antigenicity; however, chronic immunological responses and associated calcification still commonly occur. A heart valve formed from an unfixed bovine pericardium (BP) extracellular matrix (ECM) scaffold, in which antigenic burden has been eliminated or significantly reduced, has potential to overcome deficiencies of current bioprostheses. Decellularization and antigen removal methods frequently use sequential solutions extrapolated from analytical chemistry approaches to promote solubility and removal of tissue components from resultant ECM scaffolds. However, the extent to which such prefractionation strategies may inhibit removal of antigenic tissue components has not been explored. We hypothesize that presence of magnesium in prefractionation steps causes DNA precipitation and reduces removal of nuclear-associated antigenic proteins. Keeping all variables consistent bar the addition or absence of magnesium (2 mM magnesium chloride hexahydrate), residual BP ECM scaffold antigenicity and removed antigenicity were assessed, along with residual and removed DNA content, ECM morphology, scaffold composition, and recellularization potential. Furthermore, we used proteomic methods to determine the mechanism by which magnesium presence or absence affects scaffold residual antigenicity. This study demonstrates that absence of magnesium from antigen removal solutions enhances solubility and subsequent removal of antigenic nuclear-associated proteins from BP. We therefore conclude that the primary mechanism of action for magnesium removal during antigen removal processes is avoidance of DNA precipitation, facilitating solubilization and removal of nuclear-associated antigenic proteins. Future studies are

  13. GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes.

    PubMed Central

    Elefanty, A G; Antoniou, M; Custodio, N; Carmo-Fonseca, M; Grosveld, F G

    1996-01-01

    The nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse nucleoplasmic localization. These foci, which were preferentially found adjacent to nucleoli or at the nuclear periphery, did not represent sites of active transcription or binding of GATA-1 to consensus sites in the beta-globin loci. Immunoelectron microscopy demonstrated the presence of intensely labelled structures likely to represent the GATA-1 foci seen by immunofluorescence. The GATA-1 nuclear bodies differed from previously described nuclear structures and there was no co-localization with nuclear antigens involved in RNA processing or other ubiquitous (Spl, c-Jun and TBP) or haemopoietic (NF-E2) transcription factors. Interestingly, GATA-2 and GATA-3 proteins also localized to the same nuclear bodies in cell lines co-expressing GATA-1 and -2 or GATA-1 and -3 gene products. This pattern of distribution is, thus far, unique to the GATA transcription factors and suggests a protein-protein interaction with other components of the nuclear bodies via the GATA zinc finger domain. Images PMID:8617207

  14. NRP/B, a Novel Nuclear Matrix Protein, Associates With p110RB and Is Involved in Neuronal Differentiation

    PubMed Central

    Kim, Tae-Aug; Lim, Jinkyu; Ota, Setsuo; Raja, Sandhya; Rogers, Rick; Rivnay, Benjamin; Avraham, Hava; Avraham, Shalom

    1998-01-01

    The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain–like structure in the predicted NH2 terminus, and a “kelch motif” in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110RB) is found to be associated with the nuclear matrix and overexpression of p110RB induces neuronal differentiation, we investigated whether NRP/B is associated with p110RB. Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110RB during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110RB and participates in the regulation of neuronal process formation. PMID:9566959

  15. 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.

  16. Muscular dystrophy-associated SUN1 and SUN2 variants disrupt nuclear-cytoskeletal connections and myonuclear organization.

    PubMed

    Meinke, Peter; Mattioli, Elisabetta; Haque, Farhana; Antoku, Susumu; Columbaro, Marta; Straatman, Kees R; Worman, Howard J; Gundersen, Gregg G; Lattanzi, Giovanna; Wehnert, Manfred; Shackleton, Sue

    2014-09-01

    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.

  17. 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

  18. 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.

  19. 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

  20. 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.

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

    PubMed

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

    2016-06-03

    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.

  2. Post Cold War Nuclear Weapons Policy

    DTIC Science & Technology

    2012-03-20

    contrary position are those, like Scott D. Sagan , who believe that more nuclear armed states contribute to instability and a greater potential for...direct conflict with the NPT). According to Sagan and those who agree with him more nuclear armed states will lead to even more proliferation as new...Harvard Magazine, volume 103, issue 1, 34-35. 29 David Cortright, Overcoming Nuclear Dangers, 2. 30 Scott D. Sagan and Kenneth N. Waltz, The Spread of

  3. Decreased Expression of Nuclear p300 Is Associated with Disease Progression and Worse Prognosis of Melanoma Patients

    PubMed Central

    Rotte, Anand; Bhandaru, Madhuri; Cheng, Yabin; Sjoestroem, Cecilia; Martinka, Magdalena; Li, Gang

    2013-01-01

    Background Genomic instability due to UV radiation is one of the leading causes for melanoma. Histone acetyltransferase p300 plays an indispensible role in DNA repair and maintenance of genomic integrity. The present study was performed to analyze the correlation between p300 expression, melanoma progression and patient survival. Methods Tissue microarray and immunohistochemical analysis was employed to study the expression of p300 in melanoma patients. A total of 358 melanoma patients (250 primary melanoma and 108 metastatic melanoma) were used for the study. Kaplan-Meier, univariate and multivariate Cox regression analysis, and receiver-operating characteristic curves, were used to elucidate the prognostic significance of p300 expression. Results Our results demonstrate that p300 is expressed in both nucleus and cytoplasm but the nuclear expression of p300 is predominant. The progression of disease from dysplastic nevi to primary melanoma and to metastatic melanoma was associated with decreased nuclear and increased cytoplasmic p300 expression. Especially, the loss of nuclear and gain in cytoplasmic p300 was correlated with the progression of melanoma from AJCC stage II to stage III, which requires the migration and metastasis of cancer cells from primary sites to lymph nodes. Similarly, decrease in nuclear, and increase in cytoplasmic p300 expression correlated with worse survival of melanoma patients. Nuclear p300 but not cytoplasmic p300 could predict the patient survival independent of AJCC stage, age and gender. Conclusion Loss of nuclear p300 expression is an indicator of worse patient survival and is an independent prognostic marker for melanoma. PMID:24098694

  4. 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

  5. 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

  6. 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.

  7. 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.``

  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. Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma.

    PubMed

    van der Watt, Pauline J; Zemanay, Widaad; Govender, Dhirendra; Hendricks, Denver T; Parker, M I; Leaner, Virna D

    2014-08-01

    The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.

  10. Biological Significance of Unwinding Capability of Nuclear Matrix-Associating DNAs

    NASA Astrophysics Data System (ADS)

    Bode, J.; Kohwi, Y.; Dickinson, L.; Joh, T.; Klehr, D.; Mielke, C.; Kohwi-Shigematsu, T.

    1992-01-01

    Matrix attachment regions (MARs) are thought to separate chromatin into topologically constrained loop domains. A MAR located 5' of the human β-interferon gene becomes stably base-unpaired under superhelical strain, as do the MARs flanking the immunoglobulin heavy chain gene enhancer; in both cases a nucleation site exists for DNA unwinding. Concatemerized oligonucleotides containing the unwinding nucleation site exhibited a strong affinity for the nuclear scaffold and augmented SV40 promoter activity in stable transformants. Mutated concatemerized oligonucleotides resisted unwinding, showed weak affinity for the nuclear scaffold, and did not enhance promoter activity. These results suggest that the DNA feature capable of relieving superhelical strain is important for MAR functions.

  11. 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.

  12. 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

  13. Genome assembly of citrus leprosis virus nuclear type reveals a close association with orchid fleck virus.

    PubMed

    Roy, Avijit; 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; Brlansky, Ronald H

    2013-07-25

    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.

  14. 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.

  15. 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.

  16. Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi’s Sarcoma-Associated Herpesvirus for Viral Latency

    PubMed Central

    Zhang, Liming; Li, Yuhong; Feng, Yanling; Xu, Jianqing; Wang, Bin; Yuan, Zhenghong; Robertson, Erle S.; Cai, Qiliang

    2017-01-01

    Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi’s sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonstrated that KSHV blocks IL-4-induced STAT6 phosphorylation and retains a basal IL-13/STAT6 constitutive activation for cell survival and proliferation. However, the mechanism by which KSHV regulates STAT6 remains largely unknown. Here, we found that KSHV-encoded LANA interacts with STAT6 and promotes nuclear localization of STAT6 independent of the tyrosine 641-phosphorylation state. Moreover, nuclear localization of STAT6 is also dramatically increased in KS tissue. The latent antigen LANA induces serine protease-mediated cleavage of STAT6 in the nucleus, where the cleaved STAT6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of Replication and Transcription Activator (RTA) and in turn shut off viral lytic replication. Blockade of STAT6 by small interference RNA dramatically enhances expression of RTA, and in turn reduces KSHV-infected endothelial cell growth and colony formation. Taken together, these results suggest that nuclear localization and cleavage of STAT6 is important for modulating the viral latency and pathogenesis of KSHV. PMID:28099521

  17. Nuclear Localization and Cleavage of STAT6 Is Induced by Kaposi's Sarcoma-Associated Herpesvirus for Viral Latency.

    PubMed

    Wang, Chong; Zhu, Caixia; Wei, Fang; Gao, Shujun; Zhang, Liming; Li, Yuhong; Feng, Yanling; Tong, Yin; Xu, Jianqing; Wang, Bin; Yuan, Zhenghong; Robertson, Erle S; Cai, Qiliang

    2017-01-01

    Emerging evidence implies that STAT6 plays an important role in both the adaptive and innate immune responses to virus infection. Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic γ-herpesvirus agent associated with several human malignancies, including Kaposi's sarcoma (KS) and primary effusion lymphomas (PELs). Previously, we demonstrated that KSHV blocks IL-4-induced STAT6 phosphorylation and retains a basal IL-13/STAT6 constitutive activation for cell survival and proliferation. However, the mechanism by which KSHV regulates STAT6 remains largely unknown. Here, we found that KSHV-encoded LANA interacts with STAT6 and promotes nuclear localization of STAT6 independent of the tyrosine 641-phosphorylation state. Moreover, nuclear localization of STAT6 is also dramatically increased in KS tissue. The latent antigen LANA induces serine protease-mediated cleavage of STAT6 in the nucleus, where the cleaved STAT6 lacking transactivation domain functions as a dominant-negative regulator to repress transcription of Replication and Transcription Activator (RTA) and in turn shut off viral lytic replication. Blockade of STAT6 by small interference RNA dramatically enhances expression of RTA, and in turn reduces KSHV-infected endothelial cell growth and colony formation. Taken together, these results suggest that nuclear localization and cleavage of STAT6 is important for modulating the viral latency and pathogenesis of KSHV.

  18. The scope for nuclear selection within Termitomyces fungi associated with fungus-growing termites is limited

    PubMed Central

    2014-01-01

    Background We investigate the scope for selection at the level of nuclei within fungal individuals (mycelia) of the mutualistic Termitomyces cultivated by fungus-growing termites. Whereas in most basidiomycete fungi the number and kind of nuclei is strictly regulated to be two per cell, in Termitomyces mycelia the number of nuclei per cell is highly variable. We hypothesised that natural selection on these fungi not only occurs between mycelia, but also at the level of nuclei within the mycelium. We test this hypothesis using in vitro tests with five nuclear haplotypes of a Termitomyces species. Results First, we studied the transition from a mixture of five homokaryons (mycelia with identical nuclei) each with a different nuclear haplotype to heterokaryons (mycelia with genetically different nuclei). In vitro cultivation of this mixture for multiple asexual transfers led to the formation of multiple heterokaryotic mycelia, and a reduction of mycelial diversity over time. All heterokaryotic mycelia contained exactly two types of nucleus. The success of a heterokaryon during in vitro cultivation was mainly determined by spore production and to a lesser extent by mycelial growth rate. Second, heterokaryons invariably produced more spores than homokaryons implying that homokaryons will be outcompeted. Third, no homokaryotic ‘escapes’ from a heterokaryon via the formation of homokaryotic spores were found, despite extensive spore genotyping. Fourth, in contrast to most studied basidiomycete fungi, in Termitomyces sp. no nuclear migration occurs during mating, limiting the scope for nuclear competition within the mycelium. Conclusions Our experiments demonstrate that in this species of Termitomyces the scope for selection at the level of the nucleus within an established mycelium is limited. Although ‘mate choice’ of a particular nuclear haplotype is possible during mating, we infer that selection primarily occurs between mycelia with two types of nucleus

  19. Novel Problems Associated with Accounting and Control of Nuclear Material from Decontamination and Decommissioning and in Waste

    SciTech Connect

    Schlegel, Steven C.

    2007-01-10

    The United States is eliminating many facilities that support the nuclear weapons program. With the changing political conditions around the world and changes in military capabilities, the decreased emphasis on nuclear weapons has eliminated the need for many of the aging facilities. Since weapons program and commercial applications do not mix in the United States, the facilities in the weapons complex that no longer have a mission are being deinventoried, decontaminated, decommissioned, and dismantled/demolished. The materials from these activities are then disposed of in various ways but usually in select waste burial sites. Additionally, the waste in many historical burial sites associated with the weapons complex are being recovered, repackaged if necessary, and disposed of in either geological sites or low-level waste sites.

  20. Electron Distributions in Hexagonal Selenium and Tellurium and Monoclinic Selenium with Dilute Impurities and Associated Nuclear Quadrupole Interactions*.

    NASA Astrophysics Data System (ADS)

    Maharjan, N. B.; Paudyal, D. D.; Mishra, D. R.; Byahut, S.; Aryal, M. M.; Cho, Hwa-Suck; Scheicher, R. H.; Chow, Lee; Jeong, Junho; Das, T. P.

    2006-03-01

    The electron structures of Selenium chains and rings with Te impurities in hexagonal and monoclinic structures respectively and Se impurities in Te chains in hexagonal lattice have been studied using Hartree-Fock cluster model including many-body effects, including lattice relaxation effects. The calculated electronic wave-functions are utilized to obtain ^77Se and ^125Te nuclear quadrupole coupling constants e^2qQ and asymmetry parameters η and compared with available experimental data from Mossbauer and perturbed angular correlation measurements. From our results, the expected nature of nuclear quadrupole interactions associated with Sb impurities will be discussed. *Supported by NSF US-Nepal Program and UGC Nepal **Also at UCF, Orlando

  1. 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.

  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. High levels of nuclear heat-shock factor 1 (HSF1) are associated with poor prognosis in breast cancer.

    PubMed

    Santagata, Sandro; Hu, Rong; Lin, Nancy U; Mendillo, Marc L; Collins, Laura C; Hankinson, Susan E; Schnitt, Stuart J; Whitesell, Luke; Tamimi, Rulla M; Lindquist, Susan; Ince, Tan A

    2011-11-08

    Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to heat and a wide variety of other stressors. We previously reported that HSF1 promotes the survival and proliferation of malignant cells. At this time, however, the clinical and prognostic significance of HSF1 in cancer is unknown. To address this issue breast cancer samples from 1,841 participants in the Nurses' Health Study were scored for levels of nuclear HSF1. Associations of HSF1 status with clinical parameters and survival outcomes were investigated by Kaplan-Meier analysis and Cox proportional hazard models. The associations were further delineated by Kaplan-Meier analysis using publicly available mRNA expression data. Our results show that nuclear HSF1 levels were elevated in ∼80% of in situ and invasive breast carcinomas. In invasive carcinomas, HSF1 expression was associated with high histologic grade, larger tumor size, and nodal involvement at diagnosis (P < 0.0001). By using multivariate analysis to account for the effects of covariates, high HSF1 levels were found to be independently associated with increased mortality (hazards ratio: 1.62; 95% confidence interval: 1.21-2.17; P < 0.0013). This association was seen in the estrogen receptor (ER)-positive population (hazards ratio: 2.10; 95% confidence interval: 1.45-3.03; P < 0.0001). In public expression profiling data, high HSF1 mRNA levels were also associated with an increase in ER-positive breast cancer-specific mortality. We conclude that increased HSF1 is associated with reduced breast cancer survival. The findings indicate that HSF1 should be evaluated prospectively as an independent prognostic indicator in ER-positive breast cancer. HSF1 may ultimately be a useful therapeutic target in cancer.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence

    PubMed Central

    Jin, Jing; Jung, Hae Yoen; Lee, Kyu Ho; Yi, Nam-Joon; Suh, Kyung-Suk; Jang, Ja-June; Lee, Kyoung-Bun

    2016-01-01

    Background: Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients. Methods: HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining. Results: The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015). Conclusions: Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs. PMID:27086597

  9. DNA-PK/Ku complex binds to latency-associated nuclear antigen and negatively regulates Kaposi's sarcoma-associated herpesvirus latent replication

    SciTech Connect

    Cha, Seho; Lim, Chunghun; Lee, Jae Young; Song, Yoon-Jae; Park, Junsoo; Choe, Joonho; Seo, Taegun

    2010-04-16

    During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-terminal region of LANA. LANA was phosphorylated by DNA-PK and overexpression of Ku70, but not Ku86, impaired transient replication. The efficiency of transient replication was significantly increased in the HCT116 (Ku86 +/-) cell line, compared to the HCT116 (Ku86 +/+) cell line, suggesting that the DNA-PK/Ku complex negatively regulates KSHV latent replication.

  10. Molecular anatomy of tunicate senescence: reversible function of mitochondrial and nuclear genes associated with budding cycles.

    PubMed

    Kawamura, Kaz; Kitamura, Seigo; Sekida, Satoko; Tsuda, Masayuki; Sunanaga, Takeshi

    2012-11-01

    Zooids of the asexual strain of Polyandrocarpa misakiensis have a lifespan of 4-5 months; before dying, they produce many buds, enabling continuation of the strain. This study was designed to investigate the nature of gene inactivation and reactivation during this continuous process of senescence and budding. During senescence, the zooidal epidermis showed acid β-galactosidase activity, lost proliferating cell nuclear antigen immunoreactivity and became ultrastructurally worn, indicating that the epidermis is a major tissue affected by the ageing process. Semi-quantitative PCR analysis showed that the genes encoding mitochondrial respiratory chains (MRCs) engaged in decreased transcriptional activity in senescent adults compared with younger adults. The results of in situ hybridization showed that the epidermis dramatically attenuates MRC expression during ageing but restores gene activity when budding commences. During budding and ageing, the nuclear gene Eed (a polycomb group component) was activated and inactivated in a pattern similar to that observed in MRCs. In buds, RNA interference (RNAi) of Eed attenuated Eed transcripts but did not affect the gene expression of pre-activated MRCs. A tunicate humoral factor, TC14-3, could induce Eed, accompanying the reactivation of MRC in adult zooids. When RNAi of Eed and Eed induction were performed simultaneously, zooidal cells and tissues failed to engage in MRC reactivation, indicating the involvement of Eed in MRC activation. Results of this study provide evidence that the mitochondrial gene activities of Polyandrocarpa can be reversed during senescence and budding, suggesting that they are regulated by nuclear polycomb group genes.

  11. 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.

  12. 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.

  13. Complex alternative cytoplasmic protein isoforms of the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 generated through noncanonical translation initiation.

    PubMed

    Toptan, Tuna; Fonseca, Lidia; Kwun, Hyun Jin; Chang, Yuan; Moore, Patrick S

    2013-03-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) protein is constitutively expressed in all KSHV-infected cells, as well as in all forms of KSHV-associated malignancies. LANA1 is a multifunctional KSHV oncoprotein containing multiple repeat sequences that is important for viral episome maintenance and the regulation of cellular and viral gene expression. We characterize here multiple LANA1 isoforms and show that ∼50% of LANA1 is naturally generated as N-terminally truncated shoulder proteins that are detected on SDS-PAGE as faster-migrating shoulder bands designated LANA1(S). Higher-molecular-weight LANA1(S) isoforms initiate downstream at noncanonical sites within the N-terminal region, whereas lower-molecular-weight LANA1(S) isoforms initiate downstream within the central repeat 1 domain. LANA1(S) proteins lack an N-terminal nuclear localization signal motif, and some isoforms differ from full-length, canonical LANA1 by localizing to perinuclear and cytoplasmic sites. Although LANA1 has until now been assumed to be solely active in the nucleus, this finding indicates that this major KSHV oncoprotein may have cytoplasmic activities as well. KSHV overcomes its limited genetic coding capacity by generating alternatively initiated protein isoforms that may have distinct biological functions.

  14. HLA-DR antigens in systemic lupus erythematosus: association with specificity of autoantibody responses to nuclear antigens.

    PubMed Central

    Smolen, J S; Klippel, J H; Penner, E; Reichlin, M; Steinberg, A D; Chused, T M; Scherak, O; Graninger, W; Hartter, E; Zielinski, C C

    1987-01-01

    HLA-DR antigens and autoantibodies to the nuclear or cytoplasmic antigens Ro/SSA, La/SSB, Sm, and RNP were determined in North American and Austrian patients with systemic lupus erythematosus (SLE). Analysis of the association of antibodies to these ribonucleic acid (RNA)-protein antigens with HLA-DR antigens showed that HLA-DR3 was related to the presence of anti-Ro/SSA or anti-La/SSB, or both. In contrast, anti-Sm or anti-RNP, or both were associated with HLA-DR4. HLA-DR5 was associated with absence of these autoantibodies. The data extend evidence for the complexity and heterogeneity of SLE. Moreover, they indicate that, in SLE, genes linked to those coding for HLA-DR antigens, are related to the specificity of autoantibody responses rather than to the primary immunological abnormalities of this disorder. PMID:3498447

  15. The challenges and future of oral drug delivery: An interview with David Brayden.

    PubMed

    Brayden, David J

    2016-12-01

    David Brayden speaks to Hannah Makin, Commissioning Editor: David Brayden is a Full Professor (Advanced Drug Delivery) at the School of Veterinary Medicine, University College Dublin (UCD) and also a Fellow of the UCD Conway Institute. Following a PhD in Pharmacology at the University of Cambridge, UK (1989), and a postdoctoral research fellowship at Stanford University, CA, USA, he set up Elan Biotechnology Research's in vitro pharmacology laboratory in Dublin (1991). At Elan, he became a senior scientist and project manager of several of Elan's joint-venture drug delivery research collaborations with US biotech companies. In 2001, he joined UCD as a lecturer in veterinary pharmacology and was appointed Associate Professor in 2006 and Full Professor in 2014. He was a Director of the Science Foundation Ireland Research Cluster (The Irish Drug Delivery Research Network) from 2007 to 2013, is a Deputy Coordinator of an FP7 Consortium on oral peptides in nanoparticles ('TRANS-INT', 2012-2017), and is a Co-Principal Investigator in 'CURAM', Science Foundation Ireland's new Centre for Medical Devices (2014-2020 [ 1 ]). He was made a Fellow of the Controlled Release Society in 2012. He is the author or co-author of >200 research publications and patents. D Brayden serves on the Editorial Advisory Boards of Drug Discovery Today, European Journal of Pharmaceutical Sciences, Advanced Drug Delivery Reviews and the Journal of Veterinary Pharmacology and Therapeutics, and is an Associate Editor of Therapeutic Delivery. D Brayden works as an independent consultant for drug delivery companies.

  16. 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).

  17. 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.

  18. David Bohm's Hidden Variables Interpretation of Quantum Mechanics

    NASA Astrophysics Data System (ADS)

    Hall, Ned; Feldman, Gary; Wulsin, Wells

    2001-04-01

    This talk presents the hidden variables interpretation of quantum mechanics as proposed by David Bohm in 1952. Using a pilot-wave, Bohm’s theory reproduces the standard predictions of quantum mechanics while at the same time postulating that particles at all times are localized at definite positions. By way of introduction, the foundational issue of the quantum mechanics measurement problem will be discussed. The talk will then focus on how Bohm’s formulation of a hidden variables theory stands up to philosophical examination. Traditional objections to the theory, such as the EPR paradox, will be addressed, as well as the deeper metaphysical implications it holds for our view of the universe.

  19. STS-107 Crew Interviews: David Brown MS1

    NASA Technical Reports Server (NTRS)

    2002-01-01

    STS-107 Mission Specialist 1 David Brown is seen during this preflight interview where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his career. Brown outlines his role in the mission in general, and specifically during the conducting of on-board science experiments. Brown discusses the following instruments and experiments in detail: ARMS (Advanced Respiratory Monitoring System), MEIDEX (Mediterranean Israeli Dust Experiment), Combustion Module 2, and FREESTAR (Fast Reaction Enables Science Technology and Research). He also describes the new primary payload carrier, the SPACEHAB research double module which doubles the amount of space available for research. Brown shares his thoughts about the importance of international cooperation in mission planning and the need for scientific research in space.

  20. 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.

  1. 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.

  2. 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.

  3. Highlights of the Annual Congress of the European Association of Nuclear Medicine, Helsinki 2004, and a dash of horizon scanning.

    PubMed

    Ell, Peter J

    2005-01-01

    The Annual Congress of the European Association of Nuclear Medicine represents the major scientific and professional event in the field of nuclear medicine in Europe. Specialists from all allied professions meet to discuss the latest findings and discoveries. A very large industrial exhibition demonstrates the latest technological innovations and developments. This Highlights Lecture summarises the scientific and medical advances discussed at this important gathering. The lecture covers a significant proportion of the data presented and/or discussed in up-to-date reviews, and places some of the trends encountered in the context of the evolution of the field as a whole. There is much food for thought in most areas of nuclear medicine: advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in known areas of clinical application such as neurology and psychiatry, cardiology, oncology, endocrine disorders, paediatrics, nephro-urology and musculoskeletal disorders. This Highlights Lecture is, however, only a brief resume of the vast amount of data discussed, which can be found in much greater detail in the Congress Proceedings, published as volume 31, supplement 2 of Eur J Nucl Med Mol Imaging in August 2004.

  4. 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

  5. Characterization of the bipartite nuclear localization signal of protein LANA2 from Kaposi's sarcoma-associated herpesvirus.

    PubMed Central

    Muñoz-Fontela, Cesar; Rodríguez, Estefanía; Nombela, Cesar; Arroyo, Javier; Rivas, Carmen

    2003-01-01

    LANA2 is a nuclear latent protein detected exclusively in Kaposi's sarcoma-associated herpesvirus-infected B cells. The protein inhibits p53-dependent transactivation and apoptosis, suggesting an important role in the transforming activity of the virus. To explore the molecular mechanisms of its nuclear localization, fusion proteins of green fluorescent protein (EGFP) and deletion constructs of LANA2 were expressed in HeLa cells. Only the fragment comprising amino acid residues 355-440 of LANA2 localized in the cell nucleus. This fragment contains two closely located basic domains and forms a putative bipartite nuclear localization signal (NLS). The putative LANA2 NLS was able to target EGFP to the nucleus consistently. Site-directed mutation analyses demonstrated that LANA2 contains a functional bipartite NLS between amino acid positions 367 and 384. In addition, analysis of cells transfected with a cytoplasmic LANA2 mutant revealed that an appropriate subcellular localization may be crucial to regulate p53 activity. PMID:12767255

  6. TSH stimulates 32P-labeling of thyroid nuclear HMG 14, a protein associated with actively transcribed chromatin

    SciTech Connect

    Cooper, E.; Palmer, R.J.; Spaulding, S.W.

    1982-04-01

    Thyroid slices were incubated with 32P with or without TSH. 32P-labeling of acid-soluble nuclear proteins was then examined by two-dimensional polyacrylamide gel electrophoresis and autoradiography. We found that TSH enhanced the labeling of the high mobility group protein HMG 14, a protein that is preferentially associated with actively transcribed chromatin. This observation suggests that changes in HMG 14 phosphorylation may be involved in mediating TSH-induced effects on the structure and function of active chromatin.

  7. Overexpression of an enzymically inactive interleukin-1-receptor-associated kinase activates nuclear factor-kappaB.

    PubMed Central

    Maschera, B; Ray, K; Burns, K; Volpe, F

    1999-01-01

    Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT), but not a kinase-defective mutant with Asp340 replaced by an asparagine residue (IRAK-Asp340Asn), is highly phosphorylated and is capable of auto-phosphorylation in vitro. Overexpression of both IRAK-WT and IRAK-Asp340Asn caused activation of nuclear factor kappaB, suggesting that the kinase activity of IRAK is not required outside of the IL-1R complex. PMID:10191251

  8. Nuclear localization of heme oxygenase-1 is associated with tumor progression of head and neck squamous cell carcinomas.

    PubMed

    Gandini, Norberto A; Fermento, María E; Salomón, Débora G; Blasco, Jorge; Patel, Vyomesh; Gutkind, J Silvio; Molinolo, Alfredo A; Facchinetti, María M; Curino, Alejandro C

    2012-10-01

    The expression of heme oxygenase-1 (HO-1) was shown to be increased in multiple tumors compared with their surrounding healthy tissues and was also observed to be up-regulated in oral squamous cell carcinomas (OSCC). However, conflicting results were obtained and little information is available regarding HO-1 significance in head and neck squamous cell carcinoma (HNSCC). Therefore, the aim of the present study was to perform a wide screening of HO-1 expression in a large collection of human primary HNSCCs and to correlate the results with clinical and pathological parameters. For this purpose, we investigated the expression of this protein by immunohistochemistry (IHC) in tissue microarrays (TMAs) of HNSCC and in an independent cohort of paraffin-embedded tumor specimens. HO-1 expression was further validated by real-time qPCR performed on selected laser capture-microdissected (LCM) oral tissue samples. Both the number of HO-1-positive samples and HO-1 immunoreactivity in the cancerous tissues were significantly higher than those in the non-tumor tissues. These results were confirmed at the mRNA level. Interestingly, HO-1 localization was observed in the nucleus, and the rate of nuclear HO-1 in HNSCC was higher than that in non-malignant tissues. Nuclear HO-1 was observed in HNSCC cell lines and increased even further following hemin treatment. Analysis of HO-1 expression and sub-cellular localization in a mouse model of squamous cell carcinoma (SCC) and in human HNSCC revealed that nuclear HO-1 increases with tumor progression. Taken together, these results demonstrate that HO-1 is up-regulated in HNSCC and that nuclear localization of HO-1 is associated with malignant progression in this tumor type.

  9. 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.

  10. 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…

  11. 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…

  12. 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...

  13. High expression level and nuclear localization of Sam68 are associated with progression and poor prognosis in colorectal cancer

    PubMed Central

    2013-01-01

    Background Src-associated in mitosis (Sam68; 68 kDa) has been implicated in the oncogenesis and progression of several human cancers. The aim of this study was to investigate the clinicopathologic significance of Sam68 expression and its subcellular localization in colorectal cancer (CRC). Methods Sam68 expression was examined in CRC cell lines, nine matched CRC tissues and adjacent noncancerous tissues using reverse transcription (RT)-PCR, quantitative RT-PCR and Western blotting. Sam68 protein expression and localization were determined in 224 paraffin-embedded archived CRC samples using immunohistochemistry. Statistical analyses were applied to evaluate the clinicopathologic significance. Results Sam68 was upregulated in CRC cell lines and CRC, as compared with normal tissues; high Sam68 expression was detected in 120/224 (53.6%) of the CRC tissues. High Sam68 expression correlated significantly with poor differentiation (P = 0.033), advanced T stage (P < 0.001), N stage (P = 0.023) and distant metastasis (P = 0.033). Sam68 nuclear localization correlated significantly with poor differentiation (P = 0.002) and T stage (P =0.021). Patients with high Sam68 expression or Sam68 nuclear localization had poorer overall survival than patients with low Sam68 expression or Sam68 cytoplasmic localization. Patients with high Sam68 expression had a higher risk of recurrence than those with low Sam68 expression. Conclusions Overexpression of Sam68 correlated highly with cancer progression and poor differentiation in CRC. High Sam68 expression and Sam68 nuclear localization were associated with poorer overall survival. PMID:23937454

  14. Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

    PubMed

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

    2012-11-01

    Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

  15. Expression of DNAJB12 or DNAJB14 causes coordinate invasion of the nucleus by membranes associated with a novel nuclear pore structure.

    PubMed

    Goodwin, Edward C; Motamedi, Nasim; Lipovsky, Alex; Fernández-Busnadiego, Rubén; DiMaio, Daniel

    2014-01-01

    DNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER) that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, which we designate DJANGOS for DNAJ-associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70 and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are evenly distributed underneath the nuclear envelope and are of uniform size in any one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and sheets that connect to the nuclear envelope via a unique configuration of membranes, in which the nuclear pore complex appears anchored exclusively to the outer nuclear membrane, allowing both the inner and outer nuclear membranes to flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS break down rapidly during cell division and reform synchronously in the daughter cell nuclei, demonstrating that they are dynamic structures that undergo coordinate formation and dissolution. Genetic studies showed that the chaperone activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis of these structures will provide insight into nuclear pore formation and function, activities of molecular chaperones, and mechanisms that maintain membrane identity.

  16. Deep sequencing unearths nuclear mitochondrial sequences under Leber's hereditary optic neuropathy-associated false heteroplasmic mitochondrial DNA variants.

    PubMed

    Petruzzella, Vittoria; Carrozzo, Rosalba; Calabrese, Claudia; Dell'Aglio, Rosa; Trentadue, Raffaella; Piredda, Roberta; Artuso, Lucia; Rizza, Teresa; Bianchi, Marzia; Porcelli, Anna Maria; Guerriero, Silvana; Gasparre, Giuseppe; Attimonelli, Marcella

    2012-09-01

    Leber's hereditary optic neuropathy (LHON) is associated with mitochondrial DNA (mtDNA) ND mutations that are mostly homoplasmic. However, these mutations are not sufficient to explain the peculiar features of penetrance and the tissue-specific expression of the disease and are believed to be causative in association with unknown environmental or other genetic factors. Discerning between clear-cut pathogenetic variants, such as those that appear to be heteroplasmic, and less penetrant variants, such as the homoplasmic, remains a challenging issue that we have addressed here using next-generation sequencing approach. We set up a protocol to quantify MTND5 heteroplasmy levels in a family in which the proband manifests a LHON phenotype. Furthermore, to study this mtDNA haplotype, we applied the cybridization protocol. The results demonstrate that the mutations are mostly homoplasmic, whereas the suspected heteroplasmic feature of the observed mutations is due to the co-amplification of Nuclear mitochondrial Sequences.

  17. [Nuclear gene involves in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation].

    PubMed

    Zhao, Su Ying; Zhang, Hai Jun; Xu, Chun Hong; Shan, Xiang Nian

    2006-02-01

    The human mitochondrial 12S rRNA gene mutation at position 1555 associated with non-syndromic deafness and aminoglycoside-induced deafness. Family of Huaiyin in Jiangsu is one of the biggest non-syndromic deafness family in the world. In this family, deafness is maternally inherited. After establishing immortal lymphoblastoid cell lines of the family by EB virus, we analysed 17 lymphoblastoid cell lines derived, respectively, from symptomatic, asymptomatic and controll members of the family. Compared with control members, symptomatic and asymptomatic members both exhibited significant decreases in the rate of growth as well as in the rates of mitochondrial protein synthesis. But the extent of decreases is different and the severity of mitochondrial defect is related with its clinical phenotype. These results supported that the nuclear factor involves in the phenotypic manifestation of the non-syndromic deafness associated with the A1555G mutation.

  18. 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.

  19. Apoptosis and nuclear factor-kappa B: a tale of association and dissociation.

    PubMed

    Aggarwal, B B

    2000-10-15

    It is not clear why on treatment with certain killer cytokines or chemotherapeutic agents, some cells undergo apoptosis while others do not. The delineation of sensitivity/resistance pathways should provide a more specific therapy for cancer and other hyperproliferative diseases. Most cells die either by apoptosis or by necrosis. The biochemical pathway that mediates these two modes of cell death has recently been described. The nuclear factor (NF)-kappa B and the genes regulated by this transcription factor have been shown to play a critical role in induction of resistance to killer agents. Thus, inhibitors of NF-kappa B activation have a potential in overcoming resistance to apoptosis induced by various agents. The evidence for and against such a notion is discussed.

  20. Identification of a 120-kDa protein associated with aromatic hydrocarbon receptor nuclear translocator.

    PubMed

    Hossain, A; Kikuchi, H; Ikawa, S; Sagami, I; Watanabe, M

    1995-07-06

    The aromatic hydrocarbon receptor nuclear translocator (ARNT) is a basic helix-loop-helix-PAS protein which forms a heterodimer with aromatic hydrocarbon receptor (AHR), this heterodimer mediating the signal transduction in response to the various xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and directly interacting with target genes by binding to xenobiotic responsive elements. An anti-ARNT antibody was raised in rabbits against the bacterially expressed ARNT of amino acids 21-328 from the N-terminal. Using this antibody, besides ARNT itself, we detected at least one protein, 120 kDa, in the immunoprecipitate of anti-ARNT antibodies in HepG2 cells as well as in Hepa-1 cells. However, this protein is not present in the immunoprecipitate of the anti-AHR antisera nor in that of the preimmune sera of the rabbits used for the immunization.

  1. 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.

  2. Nuclear-Cytoplasmic Conflict in Pea (Pisum sativum L.) Is Associated with Nuclear and Plastidic Candidate Genes Encoding Acetyl-CoA Carboxylase Subunits

    PubMed Central

    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. PMID:25789472

  3. PML-associated repressor of transcription (PAROT), a novel KRAB-zinc finger repressor, is regulated through association with PML nuclear bodies

    SciTech Connect

    Fleischer, Sandra; Wiemann, Stefan; Will, Hans; Hofmann, Thomas G. . E-mail: t.hofmann@dkfz.de

    2006-04-01

    Promyelocytic leukemia nuclear bodies (PML-NBs) are implicated in transcriptional regulation. Here we identify a novel transcriptional repressor, PML-associated repressor of transcription (PAROT), which is regulated in its repressor activity through recruitment to PML-NBs. PAROT is a Krueppel-associated box ( KRAB) zinc-finger (ZNF) protein, which comprises an amino terminal KRAB-A and KRAB-B box, a linker domain and 8 tandemly repeated C{sub 2}H{sub 2}-ZNF motifs at its carboxy terminus. Consistent with its domain structure, when tethered to DNA, PAROT represses transcription, and this is partially released by the HDAC inhibitor trichostatin A. PAROT colocalizes with members of the heterochromatin protein 1 (HP1) family and with transcriptional intermediary factor-1{beta}/KRAB-associated protein 1 (TIF-1{beta}/KAP1), a transcriptional corepressor for the KRAB-ZNF family. Interestingly, PML isoform IV, in contrast to PML-III, efficiently recruits PAROT and TIF-1{beta} from heterochromatin to PML-NBs. PML-NB recruitment of PAROT partially releases its transcriptional repressor activity, indicating that PAROT can be regulated through subnuclear compartmentalization. Taken together, our data identify a novel transcriptional repressor and provide evidence for its regulation through association with PML-NBs.

  4. 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

  5. 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

  6. The PML-nuclear inclusion of human supraoptic neurons: a new compartment with SUMO-1- and ubiquitin-proteasome-associated domains.

    PubMed

    Villagra, Nuria T; Navascues, Joaquin; Casafont, Iñigo; Val-Bernal, J Fernando; Lafarga, Miguel; Berciano, Maria T

    2006-01-01

    It is well known that the cell nucleus is organized in structural and functional compartments involved in transcription, RNA processing and protein modifications such as conjugation with SUMO-1 and proteolysis. Promyelocytic leukaemia (PML) bodies are dynamic nuclear structures that concentrate PML protein, SUMO-1 and several sumoylated and non-sumoylated protein regulators of nuclear functions. PML bodies and their associated CBP has been involved in neuronal survival. By light and electron microscopy immunocytochemistry and in situ hybridization we reported the presence, in non-pathological conditions, of a large PML-nuclear inclusion (PML-NI) in human supraoptic neurons. This inclusion appears as a single nuclear structure composed of a capsule enriched in PML, SUMO-1 and CBP proteins and a central lattice of filaments immunoreactive for class III beta-tubulin, ubiquitinated proteins and proteasomes. Furthermore, the PML-NI concentrates the SUMO-conjugating enzyme E2 (UBC9). The PML-NI may be considered a nuclear factory involved in sumoylation and proteolysis via ubiquitin-proteasome system, two nuclear pathways engaged in the control of the nucleoplasmic concentration of active transcriptional regulators. Interestingly, the structural and molecular organization of the PML-NI is related to the Marinesco bodies, age-associated ubiquitinated intranuclear inclusions, and to the intranuclear rodlets enriched in class III beta-tubulin, which are nuclear structures markedly decreased in Alzheimer's disease.

  7. 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.

  8. 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.

  9. Latency-associated nuclear antigen of Kaposi sarcoma-associated herpesvirus promotes angiogenesis through targeting notch signaling effector Hey1.

    PubMed

    Wang, Xing; He, Zhiheng; Xia, Tian; Li, Xiaofan; Liang, Deguang; Lin, Xianzhi; Wen, Hao; Lan, Ke

    2014-04-01

    Notch signaling has been implicated in the pathogenesis of Kaposi sarcoma. Kaposi sarcoma is an angioproliferative neoplasm that originates from Kaposi sarcoma-associated herpesvirus (KSHV) infection. Previously, we showed that the KSHV LANA protein can stabilize intracellular Notch in KSHV-infected tumor cells and promote cell proliferation. However, whether Notch signaling functions in pathologic angiogenesis of Kaposi sarcoma remains largely unknown. Hey1, an essential downstream effector of the Notch signaling pathway, has been demonstrated to play a fundamental role in vascular development. In the present study, we performed whole transcriptome, paired-end sequencing on three patient-matched clinical Kaposi sarcoma specimens and their corresponding adjacent stroma samples, with an average depth of 42 million reads per sample. Dll4, Hey1, and HeyL displayed significant upregulation in Kaposi sarcoma. Further verification based on immunohistochemistry analysis demonstrated that Hey1 was indeed highly expressed in Kaposi sarcoma lesions. Using the Matrigel plug assay, we showed that downregulation of Hey1 and γ-secretase inhibitor treatment caused dramatic reduction in the formation of new blood vessels in mice. Interestingly, LANA was responsible for the elevated level of Hey1 through inhibition of its degradation. Importantly, Hey1 stabilized by LANA promoted the neoplastic vasculature. Taken together, our data suggest that hijacking of the proangiogenic property of Hey1 by LANA is an important strategy utilized by KSHV to achieve pathologic angiogenesis and that Hey1 is a potential therapeutic target in Kaposi sarcoma.

  10. Sir David Brewster's changing ideas on the plurality of worlds

    NASA Astrophysics Data System (ADS)

    de Asúa, Miguel

    2006-06-01

    In the course of his long life the Scottish physicist David Brewster wrote copiously about the plurality of worlds. More Worlds than One (1854), perhaps his strongest statement on the question, was written as an answer to William Whewell's On the Plurality of Worlds (1853), which argued that life was a privilege of the Earth. Brewster's ideas changed drastically along the years in many crucial issues such as the habitability of the Sun and the Moon, the possibility that extraterrestrials could be different from humans, and the occupation of the Earth by intelligent races in the distant past. This paper succinctly surveys Brewster's main lines of thought about the plurality of worlds underlining the significance of his first two articles devoted exclusively to this topic. They were published in 1838 in The Monthly Chronicle, and affirm the habitability of the planets while denying that of the Moon. As is the case with many Victorian scientists, belief in pluralism was for Brewster part and parcel of a complex of ideas and attitudes in which it is hard to distinguish science from religion. I shall argue that a fair number of the shifting opinions and inconsistencies detectable in Brewster's ideas on the plurality of worlds can be attributed to the fact that these were used as pliable apologetic instruments in his scientific writings, many of which are permeated by strong religious concerns.

  11. 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

  12. Impaired protein stability and nuclear localization of NOBOX variants associated with premature ovarian insufficiency.

    PubMed

    Ferrari, Ilaria; Bouilly, Justine; Beau, Isabelle; Guizzardi, Fabiana; Ferlin, Alberto; Pollazzon, Marzia; Salerno, Mariacarolina; Binart, Nadine; Persani, Luca; Rossetti, Raffaella

    2016-10-23

    Premature ovarian insufficiency (POI) is a clinical syndrome defined by a loss of ovarian activity before the age of 40. Its pathogenesis is still largely unknown, but increasing evidences support a genetic basis in most cases. Among these, heterozygous mutations in NOBOX, a homeobox gene encoding a transcription factor expressed specifically by oocyte and granulosa cells within the ovary, have been reported in ∼6% of women with sporadic POI. The pivotal role of NOBOX in early folliculogenesis is supported by findings in knock-out mice. Here, we report the genetic screening of 107 European women with idiopathic POI, recruited in various settings, and the molecular and functional characterization of the identified variants to evaluate their involvement in POI onset. Specifically, we report the identification of two novel and two recurrent heterozygous NOBOX variants in 7 out of 107 patients, with a prevalence of 6.5% (upper 95% confidence limit of 11.17%). Furthermore, immunolocalization, Western Blot and transcriptional assays conducted in either HEK293T or CHO cells revealed that all the studied variants (p.R44L, p.G91W, p.G111R, p.G152R, p.K273*, p.R449* and p.D452N) display variable degrees of functional impairment, including defects in transcriptional activity, autophagosomal degradation, nuclear localization or protein instability. Several variants conserve the ability to interact with FOXL2 in intracellular aggregates. Their inability to sustain gene expression, together with their likely aberrant effects on protein stability and degradation, make the identified NOBOX mutations a plausible cause of POI onset.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Pakistan’s Nuclear Weapons: Proliferation and Security Issues

    DTIC Science & Technology

    2009-04-01

    2007,” ibid.; SIPRI Yearbook 2007. 5 “Nuclear Notebook,” ibid. 6 “Global Fissile Material Report 2007,” International Panel on Fissile Materials...State for Foreign and Commonwealth Affairs David Miliband told the Charlie Rose Show December 15, 2008, that Islamabad’s nuclear weapons “are under...Nuclear Weapons in Pakistan,” Pakistan Security Research Unit Brief Number 22, University of Bradford, November 18, 2007. Available at http

  18. Superovulation in red deer (Cervus elaphus) and Père David's deer (Elaphurus davidianus), and fertilization rates following artificial insemination with Père David's deer semen.

    PubMed

    Argo, C M; Jabbour, H N; Goddard, P J; Webb, R; Loudon, A S

    1994-03-01

    Two comparative studies were undertaken using adult, female red and Père David's deer to examine the ovulatory response of these animals to a superovulation regimen and fertilization rates following inter- and intraspecific laparoscopic insemination. In Expt 1 six Père David's deer and 12 red deer hinds were treated during the breeding season with an intravaginal progesterone-impregnated controlled internal drug release device (CIDR) for 14 days, with 200 iu pregnant mares' serum gonadotrophin (PMSG) administered 72 h before the device was withdrawn and eight injections of ovine FSH given at 12 h intervals starting at the time of PMSG administration. Oestrous behaviour began one day after CIDR device withdrawal (Père David's deer: 24.00 +/- 2.32 h; red deer: 24.60 +/- 2.23 h). The duration of oestrus was greater in Père David's deer than in red deer (17.50 +/- 1.43 h and 8.25 +/- 3.25 h, respectively, P < 0.001). The peak LH surge of Père David's deer was 68.65 +/- 4.74 ng ml-1 occurring 29.00 +/- 2.41 h after removal of the CIDR devices. In comparison, the peak LH surge in red deer was 17.09 +/- 3.64 ng ml-1 (P < 0.001), occurring 24.00 +/- 0.00 h after CIDR device withdrawal. Pre-surge concentrations of LH were also greater (P < 0.001) in Père David's deer (1.37 +/- 0.11 ng ml-1) than in red deer hinds (0.41 +/- 0.02 ng ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Life Cycle of a Large Telescope: the David Dunlap Observatory

    NASA Astrophysics Data System (ADS)

    Jarrell, Richard

    2009-01-01

    When it went into operation in 1935, the 74-inch reflector at the David Dunlap Observatory was the world's second largest and most sophisticated telescope. Designed specifically for stellar spectroscopy, almost all work performed with it until the early 1950s was limited to that specialty. Most University of Toronto staff were expected to contribute to the observatory's programme. However, as the staff expanded and newer research specialties were introduced, the telescope had to be refitted with new auxiliary equipment, or not be used at all. By the late 1960s, the observatory's night sky began to deteriorate due to light pollution from uncontrolled urban growth. While limited work could be performed into the 1990s, the telescope was no longer considered "large” far more powerful, versatile instruments at much superior sites were by then available. That Toronto astronomers had moved on can be demonstrated from their publication records. The end came in 2008 when the University of Toronto decided that the land's value could be used to support astronomical research in a broader sense. In response, the community, which had ignored the observatory for most of its history, and a few dissident astronomers, strongly defended its survival on a number of grounds. The narrative suggests a number of life-cycle stages: 1) maximum use of the instrument due to superior environmental and technical conditions, plus staff homogeneity; 2) application of new technologies to extend the instrument's capability in the face of diversifying research interests and decaying environmental factors; 3) fading value due to obsolescence and poor environmental factors; 4) death or metamorphosis (such as becoming an educational or historical institution). It appears that these phases apply to a number of historical cases. It is not clear, for the Dunlap Observatory, how the fourth phase will play out.

  20. [Book review] Middle American Herpetology, by Jaime Villa, Larry David Wilson, and Jerry D. Johnson

    USGS Publications Warehouse

    Scott, N.J.

    1989-01-01

    Review of: Middle American Herpetology: a bibliographic checklist. By Jaime Villa, Larry David Wilson and Jerry D. Johnson. 1988. University of Missouri Press, Columbia, Missouri 65211. 132 p., 16 color plates, $35.00 (hardcover).

  1. 78 FR 10608 - David Grant United States Air Force Medical Center Specialty Care Travel Reimbursement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-14

    ... of the Secretary David Grant United States Air Force Medical Center Specialty Care Travel... States Air Force Medical Center Specialty Care Travel Reimbursement Demonstration Project. This... MTF, and sustain readiness-related medical skills activities for the military providers....

  2. 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

  3. Assay Development and High-Throughput Screening for Inhibitors of Kaposi's Sarcoma-Associated Herpesvirus N-Terminal Latency-Associated Nuclear Antigen Binding to Nucleosomes.

    PubMed

    Beauchemin, Chantal; Moerke, Nathan J; Faloon, Patrick; Kaye, Kenneth M

    2014-07-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies, especially in immunocompromised hosts. KSHV latently infects tumor cells and persists as an extrachromosomal episome (plasmid). KSHV latency-associated nuclear antigen (LANA) mediates KSHV episome persistence. LANA binds specific KSHV sequence to replicate viral DNA. In addition, LANA tethers KSHV genomes to mitotic chromosomes to efficiently segregate episomes to daughter nuclei after mitosis. N-terminal LANA (N-LANA) binds histones H2A and H2B to attach to chromosomes. Currently, there are no specific inhibitors of KSHV latent infection. To enable high-throughput screening (HTS) of inhibitors of N-LANA binding to nucleosomes, here we develop, miniaturize, and validate a fluorescence polarization (FP) assay that detects fluorophore-labeled N-LANA peptide binding to nucleosomes. We also miniaturize a counterscreen to identify DNA intercalators that nonspecifically inhibit N-LANA binding to nucleosomes, and also develop an enzyme-linked immunosorbent assay to assess N-LANA binding to nucleosomes in the absence of fluorescence. HTS of libraries containing more than 350,000 compounds identified multiple compounds that inhibited N-LANA binding to nucleosomes. No compounds survived all counterscreens, however. More complex small-molecule libraries will likely be necessary to identify specific inhibitors of N-LANA binding to histones H2A and H2B; these assays should prove useful for future screens.

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

    PubMed

    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.

  5. Germinal Center B-Cell-Associated Nuclear Protein (GANP) Involved in RNA Metabolism for B Cell Maturation.

    PubMed

    Sakaguchi, N; Maeda, K

    2016-01-01

    Germinal center B-cell-associated nuclear protein (GANP) is upregulated in germinal center B cells against T-cell-dependent antigens in mice and humans. In mice, GANP depletion in B cells impairs antibody affinity maturation. Conversely, its transgenic overexpression augments the generation of high-affinity antigen-specific B cells. GANP associates with AID in the cytoplasm, shepherds AID into the nucleus, and augments its access to the rearranged immunoglobulin (Ig) variable (V) region of the genome in B cells, thereby precipitating the somatic hypermutation of V region genes. GANP is also upregulated in human CD4(+) T cells and is associated with APOBEC3G (A3G). GANP interacts with A3G and escorts it to the virion cores to potentiate its antiretroviral activity by inactivating HIV-1 genomic cDNA. Thus, GANP is characterized as a cofactor associated with AID/APOBEC cytidine deaminase family molecules in generating diversity of the IgV region of the genome and genetic alterations of exogenously introduced viral targets. GANP, encoded by human chromosome 21, as well as its mouse equivalent on chromosome 10, contains a region homologous to Saccharomyces Sac3 that was characterized as a component of the transcription/export 2 (TREX-2) complex and was predicted to be involved in RNA export and metabolism in mammalian cells. The metabolism of RNA during its maturation, from the transcription site at the chromosome within the nucleus to the cytoplasmic translation apparatus, needs to be elaborated with regard to acquired and innate immunity. In this review, we summarize the current knowledge on GANP as a component of TREX-2 in mammalian cells.

  6. Kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein.

    PubMed

    Lan, Ke; Verma, Subhash C; Murakami, Masanao; Bajaj, Bharat; Kaul, Rajeev; Robertson, Erle S

    2007-10-09

    Deregulation of the evolutionarily conserved Notch signaling is highly correlated with oncogenesis. Intracellular activated Notch (ICN) is a protooncogene linked to the transcription activation of a number of cellular genes involved in cell cycle regulation, differentiation, and proliferation. Stability of ICN is tightly regulated by the Sel10-mediated ubiquitin-proteasome pathway. Sel10 can function as a negative regulator of Notch and exhibits activities of a tumor-suppressor protein. This article shows that the Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) directly interacts with Sel10 and forms a complex in KSHV-infected cells. This results in suppression of ICN ubiquitination and degradation. The carboxyl terminus of LANA interacts with the F-box and WD40 domains of Sel10 and competes with ICN for binding to Sel10. This elevated level of ICN is also critical for maintaining the enhanced proliferation of KSHV-infected tumor cells. These findings describe a mechanism by which the KSHV-encoded LANA protein regulates ubiquitination of ICN mediated by the F-box component of the E3 ligase Sel10, leading to proliferation of the virus-infected cells.

  7. 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

  8. 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.

  9. 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.

  10. A nuclear protein associated with lethal heat shock of HL-60 cells.

    PubMed

    Pipkin, J L; Hinson, W G; Lyn-Cook, L E; Burns, E R; Sheehan, D; Casciano, D A

    1992-09-01

    The responses to stress in living cells are well known. Thermal stress causes decreased protein synthesis as well as rapid induction of heat shock proteins (hsps), or alternately termed stress proteins (sps). The exposure of cultured promyelocytic leukemia cells (HL-60) to a 45 degrees C lethal heat shock for 1 h elicited synthesis and phosphorylation of a polypeptide M(r) 48,000 and pI 7.5 (p 48) as visualized by two-dimensional polyacrylamide gel ultra-microelectrophoresis. p 48, which was not observed at sublethal temperatures (39 and 41 degrees C), was synthesized during all phases of the cell cycle but was phosphorylated only in G0 + G1 and S-phases. The appearance of p 48 was marked by a concomitant and reciprocal reduction in hsps or sps 70 and 90. Distinct protease V8 fragment maps of p 48, hsps 70 and 90 in conjunction with immunochemical determination indicated vast differences in their primary structures. These facts suggest that p 48 was not formed from coalesced breakdown products of hsps 70 or 90. Western blotting showed that p 48 possessed the same immunochemical determinants as two other proteins with the same molecular mass but different isoelectric points. In an association assay, p 48 was shown to bind with actins and hsp 90 from HL-60 nuclei.

  11. 76 FR 29279 - Prairie Island Nuclear Generating Plant, Units 1 and 2; Notice of Availability of the Final...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ... Reactor Regulation, U.S. Nuclear Regulatory Commission, Mail Stop O-11F1, Washington, DC 20555-0001. Ms.... David J. Wrona, Chief, Projects Branch 2, Division of License Renewal, Office of Nuclear Reactor... From the Federal Register Online via the Government Publishing Office NUCLEAR...

  12. Tissue Specificity of the Kaposi's Sarcoma-Associated Herpesvirus Latent Nuclear Antigen (LANA/orf73) Promoter in Transgenic Mice

    PubMed Central

    Jeong, Joseph H.; Hines-Boykin, Rebecca; Ash, John D.; Dittmer, Dirk P.

    2002-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is a human-oncogenic herpesvirus. Cells from KSHV-associated tumors, such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), are of endothelial and B-cell origin, respectively. KSHV persists indefinitely in these cell lineages during latent infection. Indeed, cellular latency is a hallmark of all herpesviruses that is intimately linked to their pathogenesis. We previously characterized the promoter for the KSHV latency-associated nuclear antigen LANA/orf73. LANA is required for latent episome maintenance and has also been implicated in oncogenesis. Hence, regulation of LANA expression is critical to KSHV persistence. We find that a region extending to bp −1299 upstream of the LANA transcription start site is able to drive lacZ-reporter gene expression in several lines of transgenic mice. In agreement with KSHV's natural tropism, we detected reporter gene expression in CD19-positive B cells but not in CD3-positive T cells. We also detected expression in the kidney and, at a lower level, in the liver. In contrast to KS tumors, transgene expression was localized to kidney tubular epithelium rather than vascular endothelial cells. This suggests that our promoter fragment contains all cis-regulatory elements sufficient for B-cell specificity but not those required for endothelial specificity. Alternatively, while the trans-acting factors required for LANA expression in B cells are evolutionarily conserved, those that regulate endothelial cell-specific expression are unique to humans. Our in vivo studies address a conundrum in KSHV biology: in culture, KSHV is able to infect a variety of cell types indiscriminately, while in healthy latent carriers KSHV is found in B lymphocytes. The transgenic-mouse experiments reported here suggest that tissue-restricted LANA gene expression could explain B-cell-specific viral persistence. PMID:12368345

  13. Early Detection of Ovarian Cancer by Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis

    DTIC Science & Technology

    2013-10-01

    ultrasound molecular imaging agents enhances signal intensity and detection of OVCA’ was examined in specific aim 1 described in Year-1 report...improved the detection of OVCA at early stage. This improvement in OVCA detectability was due to the enhanced ultrasound imaging signal intensity ...Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis PRINCIPAL

  14. 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

  15. 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.

  16. RAD18 and associated proteins are immobilized in nuclear foci in human cells entering S-phase with ultraviolet light-induced damage

    PubMed Central

    Watson, Nicholas B.; Nelson, Eric; Digman, Michelle; Thornburg, Joshua A.; Alphenaar, Bruce W.; McGregor, W. Glenn

    2008-01-01

    Proteins required for translesion DNA synthesis localize in nuclear foci of cells with replication-blocking lesions. The dynamics of this process were examined in human cells with fluorescence-based biophysical techniques. Photobleaching recovery and raster image correlation spectroscopy experiments indicated that involvement in the nuclear foci reduced the movement of RAD18 from diffusion-controlled to virtual immobility. Examination of the mobility of REV1 indicated that it is similarly immobilized when it is observed in nuclear foci. Reducing the level of RAD18 greatly reduced the focal accumulation of REV1 and reduced UV mutagenesis to background frequencies. Fluorescence lifetime measurements indicated that RAD18 and RAD6A or polη only transferred resonance energy when these proteins colocalized in damage-induced nuclear foci, indicating a close physical association only within such foci. Our data support a model in which RAD18 within damage-induced nuclear foci is immobilized and is required for recruitment of Y-family DNA polymerases and subsequent mutagenesis. In the absence of damage these proteins are not physically associated within the nucleoplasm. PMID:18926833

  17. 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

  18. ATHB17 enhances stress tolerance by coordinating photosynthesis associated nuclear gene and ATSIG5 expression in response to abiotic stress

    PubMed Central

    Zhao, Ping; Cui, Rong; Xu, Ping; Wu, Jie; Mao, Jie-Li; Chen, Yu; Zhou, Cong-Zhao; Yu, Lin-Hui; Xiang, Cheng-Bin

    2017-01-01

    Photosynthesis is sensitive to environmental stress and must be efficiently modulated in response to abiotic stress. However, the underlying mechanisms are not well understood. Here we report that ARABIDOPSIS THALIANA HOMEOBOX 17 (ATHB17), an Arabidopsis HD-Zip transcription factor, regulated the expression of a number of photosynthesis associated nuclear genes (PhANGs) involved in the light reaction and ATSIG5 in response to abiotic stress. ATHB17 was responsive to ABA and multiple stress treatments. ATHB17-overexpressing plants displayed enhanced stress tolerance, whereas its knockout mutant was more sensitive compared to the wild type. Through RNA-seq and quantitative real-time reverse transcription PCR (qRT-PCR) analysis, we found that ATHB17 did not affect the expression of many known stress-responsive marker genes. Interestingly, we found that ATHB17 down-regulated many PhANGs and could directly modulate the expression of several PhANGs by binding to their promoters. Moreover, we identified ATSIG5, encoding a plastid sigma factor, as one of the target genes of ATHB17. Loss of ATSIG5 reduced salt tolerance while overexpression of ATSIG5 enhanced salt tolerance, similar to that of ATHB17. ATHB17 can positively modulate the expression of many plastid encoded genes (PEGs) through regulation of ATSIG5. Taken together, our results suggest that ATHB17 may play an important role in protecting plants by adjusting expression of PhANGs and PEGs in response to abiotic stresses. PMID:28358040

  19. PSL, a nuclear cell-cycle associated antigen is increased during retinoic acid-induced differentiation of HL-60 cells.

    PubMed

    Barque, J P; Lagaye, S; Ladoux, A; Della Valle, V; Abita, J P; Larsen, C J

    1987-09-30

    PSL(p55) is a nuclear 55kD antigen present in various mammalian cell systems, which has been first identified by use of human autoimmune antibodies (Barque et al. 1983, EMBO J. 2, 743). It has been shown to be associated with interphase chromatine and to be synthesized in during the S phase of the cell cycle. In this work, we have analysed the status of PSL in promyelocytic HL-60 human cells in exponential or stationary growth, or undergoing granulocytic differentiation in presence of Retinoic acid. By use of 2-dimensional electrophoresis, PSL was found to be composed of two acidic proteins designated p55A and p55B. Unexpectedly, estimated 10-20 fold higher amounts of each species were found in cells treated for 5 days with 10(-6)M Retinoic acid, than in asynchronously growing cells or resting cells. Moreover, the p55A protein was phosphorylated during the process. On the basis of these results, PSL appears to be involved in some steps of the granulocytic differentiation process.

  20. 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.

  1. 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.

  2. Fertility-associated metabolites in bull seminal plasma and blood serum: 1H nuclear magnetic resonance analysis.

    PubMed

    Kumar, Ajeet; Kroetsch, Tom; Blondin, Patrick; Anzar, Muhammad

    2015-02-01

    Early estimation of bull fertility is highly desirable for the conservation of male genetics of endangered species and for the exploitation of genetically superior sires in artificial insemination programs. The present work was conducted as a proof-of-principle study to identify fertility-associated metabolites in dairy bull seminal plasma and blood serum using proton nuclear magnetic resonance ((1)H NMR). Semen and blood samples were collected from high- and low-fertility breeding bulls (n = 5 each), stationed at Semex, Guelph, Canada. NMR spectra of serum and seminal plasma were recorded at a resonance frequency of 500.13 MHz on a Bruker Avance-500 spectrometer equipped with an inverse triple resonance probe (TXI, 5 mm). Spectra were phased manually, baseline corrected, and calibrated against 3-(trimethylsilyl) propionic-2,2,3,3-d4 acid at 0.0 parts per million (ppm). Spectra were converted to an appropriate format for analysis using Prometab software running within MATLAB. Principal component analysis was used to examine intrinsic variation in the NMR data set, and to identify trends and to exclude outliers. Partial least square-discriminant analysis was performed to identify the significant features between fertility groups. The fertility-associated metabolites with variable importance in projections (VIP) scores >2 were citrate (2.50 ppm), tryptamine/taurine (3.34-3.38 ppm), isoleucine (0.74 ppm), and leucine (0.78 ppm) in the seminal plasma; and isoleucine (1.14 ppm), asparagine (2.90-2.94 ppm), glycogen (3.98 ppm), and citrulline (1.54 ppm) in the serum. These metabolites showed identifiable peaks, and thus can be used as biomarkers of fertility in breeding bulls.

  3. 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

  4. Comparative analysis of various donor cell types for somatic cell nuclear transfer and its association with apoptosis and senescence.

    PubMed

    Kim, Eunhye; Hyun, Sang-Hwan

    2014-01-01

    The aim of the present study was to characterize potential somatic cell nuclear transfer (SCNT) donor cells by comparing two lines of transfected cells with their non‑modified parental controls in culture. Fetal fibroblasts used in the study originated from crossbred Landrace x Yorkshire x Duroc (LYD) or Yucatan mini‑pigs. The LYD fibroblasts were modified by the transfection of a tetracycline on/off gene, whereas Yucatan fibroblasts were triple transfected with the complement regulatory factors, human decay‑accelerating factor and human CD59, as well as H‑transferase. At the 9th doubling passage, parameters associated with senescence and apoptosis, including morphology, mRNA expression (TP53, Bcl‑2, Bax) and reactive oxygen species (ROS) levels, were evaluated. Population doubling (PD) time was calculated by assessing the time required for cell numbers to double by averaging the three cell passages. Quantitative polymerase chain reaction revealed that when comparing LYD with Yucatan fibroblasts, the latter exhibited a lower relative expression of TP53 and a higher relative expression of antiproliferative Bcl‑2, which correlated with the PD time results (26 and 40 h, respectively). Tetracycline on/off transfected cell lines exhibited a lower relative expression of antiapoptotic Bcl‑2 compared with their originating LYD cells. Similarly, triple transgenic cells exhibited higher TP53 and Bax mRNA expression levels than their non‑transgenic counterparts. For ROS measurement, cells were incubated with 2',7'‑dichlorofluorescin diacetate under the same conditions and were analyzed by flow cytometry. Yucatan fibroblasts exhibited higher ROS content than LYD cells. In addition, the two transgenic cell lines produced higher ROS levels than their corresponding non‑transfected cell lines. In conclusion, these results indicate that characteristics associated with senescence and apoptosis in transfected cells during culture may affect the efficiency of

  5. Proliferating Cell Nuclear Antigen Has an Association with Prognosis and Risks Factors of Cancer Patients: a Systematic Review.

    PubMed

    Lv, Qiongying; Zhang, Juan; Yi, Yuexiong; Huang, Yue; Wang, Yong; Wang, Yijun; Zhang, Wei

    2016-11-01

    Proliferating cell nuclear antigen (PCNA) is reported as a famous marker in various tumors. A couple of articles have been published about the clinical function of PCNA on cancer progression; however, these results are conflicting in some degree. Thus, it is crucial to perform a systematic review and meta-analysis to identify their real actions. Here, we took cervical cancer and glioma as example and then pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (95 % CIs). In the present study, the PCNA expression in cervical cancer and gliomas patients was both correlated with 5-year-overall survival (OS) (HR = 4.41, 95 % CI 2.71-7.17, p = 0.000; HR = 4.40, 95 % CI 3.00-6.47, p = 0.000; respectively). In addition, a fixed effect model revealed a significant association between PCNA and FIGO stage (OR = 4.48, 95 % CI 3.48-5.77, p = 0.000) or WHO grade (OR = 5.64, 95 % CI 4.15-7.68, p = 0.000), rather than age (OR = 1.01, 95 % CI 0.71-1.43, p = 0.957; OR = 1.00, 95 % CI 0.80-1.24, p = 0.989; respectively). No heterogeneity was observed across all studies. According to funnel plot, no publication bias was reported. In conclusion, our systematic review suggests that PCNA expression is significantly associated with poor 5-year survival, advanced stage or higher WHO grade, which might be suggested as a useful prognostic and diagnostic biomarker, or an effective therapy target in cervical cancer, gliomas, or even more cancers.

  6. 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.

  7. 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.

  8. 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.

  9. Association of poly(ADP-ribose) polymerase with nuclear subfractions catalyzed with sodium tetrathionate and hydrogene peroxide crosslinks.

    PubMed

    Desnoyers, S; Kirkland, J B; Poirier, G G

    1996-06-21

    Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which catalyzes the transfer of ADP-ribose units from NAD+ to a variety of nuclear proteins under the stimulation of DNA strand break. To examine its role in DNA repair, we have been studying the interaction of PARP with other nuclear proteins using disulfide cross-linking, initiated by sodium tetrathionate (NaTT). Chinese Hamster Ovary (CHO) cells were extracted sequentially with Nonidet P40 (detergent), nucleases (DNase+RNase), and high salt (1.6 M NaCl) with and without the addition of a sulfhydryl reducing agent. The residual structures are referred to as the nuclear matrix, and are implicated in the organization of DNA repair and replication. Treatment of the cells with NaTT causes the crosslinking of PARP to the nuclear matrix. Activating PARP by pretreating the cells with H2O2 did not increase the cross-linking of PARP with the nuclear matrix, suggesting a lack of additional interaction of the enzyme with the nuclear matrix during DNA repair. Both NaTT and H2O2 induced crosslinks of PARP that were extractable with high salt. To shorten the procedure, these crosslinks were extracted from cells without nucleases and high salt treatment, using phosphate buffer. Using western blotting, these crosslinks appeared as a smear of high molecular weight species including a possible dimer of PARP at 230 kDa, which return to 116 kDa following reduction with beta-mercaptoethanol.

  10. 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.

  11. 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.

  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. cDNA cloning and characterization of Npap60: a novel rat nuclear pore-associated protein with an unusual subcellular localization during male germ cell differentiation.

    PubMed

    Fan, F; Liu, C P; Korobova, O; Heyting, C; Offenberg, H H; Trump, G; Arnheim, N

    1997-03-15

    We have cloned and characterized a cDNA, Npap60, encoding a rat nuclear pore-associated protein. The 3-kb cDNA was obtained by antibody screening of a rat testis expression library. The predicted NPAP60 contains 381 amino acids with a composition of 25.6% charged residues and is highly hydrophilic. The Npap60 gene appears to be conserved in mouse, rat, and human. Immunofluorescence studies with anti-NPAP60 fusion protein antibody show that the NPAP60 protein colocalizes with nuclear pore complexes in RAT1A cells. The expression of Npap60 is about 10-20 times higher in rat testis than in somatic tissues. The subcellular localization of NPAP60 protein changes dramatically during male germ cell differentiation, from nuclear pore complex-like staining in spermatocytes to whole nucleus staining in spermatids and finally to a nuclear surface staining in mature spermatozoa. These changes are temporally and spatially related to nuclear reorganization during male germ cell differentiation.

  14. A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95

    SciTech Connect

    Sugiura, Takeyuki Yamaguchi, Aya; Miyamoto, Kentaro

    2008-04-15

    RNF43 is a recently discovered RING finger protein that is implicated in colon cancer pathogenesis. This protein possesses growth-promoting activity but its mechanism remains unknown. In this study, to gain insight into the biological action of RNF43 we characterized it biochemically and intracellularly. A combination of indirect immunofluorescence analysis and biochemical fractionation experiments suggests that RNF43 resides in the endoplasmic reticulum (ER) as well as in the nuclear envelope. Sucrose density gradient fractionation demonstrates that RNF43 co-exists with emerin, a representative inner nuclear membrane protein in the nuclear subcompartment. The cell-free system with pure components reveals that recombinant RNF43 fused with maltose-binding protein has autoubiquitylation activity. By the yeast two-hybrid screening we identified HAP95, a chromatin-associated protein interfacing the nuclear envelope, as an RNF43-interacting protein and substantiated this interaction in intact cells by the co-immunoprecipitation experiments. HAP95 is ubiquitylated and subjected to a proteasome-dependent degradation pathway, however, the experiments in which 293 cells expressing both RNF43 and HAP95 were treated with a proteasome inhibitor, MG132, show that HAP95 is unlikely to serve as a substrate of RNF43 ubiquitin ligase. These results infer that RNF43 is a resident protein of the ER and, at least partially, the nuclear membrane, with ubiquitin ligase activity and may be involved in cell growth control potentially through the interaction with HAP95.

  15. Association of topoisomerase II with the hepatoma cell nuclear matrix: the role of intermolecular disulfide bond formation.

    PubMed

    Kaufmann, S H; Shaper, J H

    1991-02-01

    Previous studies have resulted in conflicting data regarding the recovery of the nuclear enzymes topoisomerase (topo) II and topo I in the nuclear matrix fraction. In the present study we have assessed the effect of systematically altering a single extraction procedure on the distribution of these enzymes during the subfractionation of nuclei from HTC hepatoma tissue culture cells. When nuclear monolayers (prepared by treating attached cells in situ with the neutral detergent Nonidet-P40 at 4 degrees C) were isolated in the presence of the irreversible sulfhydryl blocking reagent iodoacetamide, subsequent treatment with DNase I and RNase A followed by 1.6 M NaCl resulted in structures which were extensively depleted of intranuclear components as assessed by phase contrast microscopy and conventional transmission electron microscopy. These structures contained 12 +/- 4% of the total protein present in the original nuclear monolayers. The lamins and polypeptides with molecular weights comparable to those of actin and vimentin were the predominant polypeptides present on SDS-polyacrylamide gels. Western blotting revealed that less than 5% of the total nuclear topo II molecules were present in these structures. In contrast, when the sulfhydryl cross-linking reagent sodium tetrathionate (NaTT) was substituted for iodoacetamide, the same extraction procedure yielded structures containing components of the nucleolus and an extensive intranuclear network. These structures contained a wide variety of nonlamin, nonhistone nuclear polypeptides including 23 +/- 4% of the total nuclear topo II. SDS-polyacrylamide gel electrophoresis performed under nonreducing conditions revealed that topo II in these nuclear matrices was present as part of a large disulfide cross-linked complex. Treatment of these structures with reducing agents in 1.6 M NaCl released the topo II. In contrast, topo I did not form disulfide cross-linked oligomers and was not detectable in any of these nuclease

  16. 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

  17. 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

  18. 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.

  19. Sequence Variation Analysis of Epstein-Barr Virus Nuclear Antigen 1 Gene in the Virus Associated Lymphomas of Northern China.

    PubMed

    Sun, Lingling; Zhao, Zhenzhen; Liu, Song; Liu, Xia; Sun, Zhifu; Luo, Bing

    2015-01-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the only viral protein expressed in all EBV-positive tumors as it is essential for the maintenance, replication and transcription of the virus genome. According to the polymorphism of residue 487 in EBNA1 gene, EBV isolates can be classified into five subtypes: P-ala, P-thr, V-val, V-leu and V-pro. Whether these EBNA1 subtypes contribute to different tissue tropism of EBV and are consequently associated with certain malignancies remain to be determined. To elucidate the relationship, one hundred and ten EBV-positive lymphoma tissues of different types from Northern China, a non-NPC endemic area, were tested for the five subtypes by nested-PCR and DNA sequencing. In addition, EBV type 1 and type 2 classification was typed by using standard PCR assays across type-specific regions of the EBNA3C genes. Four EBNA1 subtypes were identified: V-val (68.2%, 75/110), P-thrV (15.5%, 17/110), V-leuV (3.6%, 4/110) and P-ala (10.9%, 12/110). The distribution of the EBNA1 subtypes in the four lymphoma groups was not significantly different (p = 0.075), neither was that of the EBV type 1/type 2 (p = 0.089). Compared with the previous data of gastric carcinoma (GC), nasopharyngeal carcinoma (NPC) and throat washing (TW) from healthy donors, the distribution of EBNA1 subtypes in lymphoma differed significantly (p = 0.016), with a little higher frequency of P-ala subtype. The EBV type distribution between lymphoma and the other three groups was significantly different (p = 0.000, p = 0.000, p = 0.001, respectively). The proportion of type 1 and type 2 mixed infections was higher in lymphoma than that in GC, NPC and TW. In lymphomas, the distribution of EBNA1 subtypes in the three EBV types was not significantly different (p = 0.546). These data suggested that the variation patterns of EBNA1 gene may be geographic-associated rather than tumor-specific and the role of EBNA1 gene variations in tumorigenesis needs more extensive and

  20. Sustaining the U.S. Air Force Nuclear Mission

    DTIC Science & Technology

    2013-01-01

    and recommend courses of action to mitigate those challenges. The goal is to identify 1 Michael Quinlan , Thinking About Nuclear Weapons: Principles... David Lilienthal visited Los Alamos in February 1946, he observed that 16 GAO, 2009; GAO, 2011. 17 See 10 U.S.C. Section 179 for the full set of... Quinlan , Michael, Thinking About Nuclear Weapons: Principles, Problems, Prospects, New York: Oxford University Press, 2009. Schlesinger, James R

  1. Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer

    PubMed Central

    Zhou, Jingcheng; Dong, Daoquan; Cheng, Ran; Wang, Yan; Jiang, Shuqi; Zhu, Yuhong; Fan, Longlong; Mao, Xiangming; Gui, Yaoting; Li, Zesong; Li, Xianxin; Shi, Bentao

    2016-01-01

    Recent studies show that Karyopherin alpha 2 (KPNA2) is up-regulated in quite a number of cancers and associated with poor prognosis. Here, we found that expression levels of KPNA2 and OCT4 are up-regulated in bladder cancer tissues and significantly associated with primary tumor stage and bladder cancer patients' poorer prognosis. Our data also showed decreased cell proliferation and migration rates of bladder cancer cell lines when the expression of KPNA2 and OCT4 was silenced. Meanwhile, cell apoptosis rate was increased. Furthermore, Co-IP and immunofluorescence assay showed the KPNA2 interacts with OCT4 and inhibits OCT4 nuclear transportation when KPNA2 was silenced. Thus, we confirmed that up-regulated KPNA2 and OCT4 expression is a common feature of bladder cancer that is correlated with increased aggressive tumor behavior. Also, we propose that KPNA2 regulates the process of OCT4 nuclear transportation in bladder cancer. PMID:27611951

  2. 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

  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. Analysis of the localization and topology of nurim, a polytopic protein tightly associated with the inner nuclear membrane.

    PubMed

    Hofemeister, Helmut; O'Hare, Peter

    2005-01-28

    Nurim is an inner nuclear membrane (INM) protein that was first isolated in a visual screen for nuclear envelope-localizing proteins. Nurim lacks an N-terminal domain characteristic of other INM proteins examined to date and may represent a class of proteins that localize to the INM by a distinct mechanism. To further characterize this protein, we constructed nurim-green fluorescent protein fusions and analyzed aspects of localization, biochemistry, and membrane topology. Results from immunoprobing and protease protection assays together with other analyses indicate that nurim (total length of 262 residues) is a six transmembrane-spanning protein and contains a hairpin turn in its C-terminal transmembrane domain, resulting in the N and C termini residing on the same side of the membrane. A loop region between the fourth and fifth transmembrane domains is exposed toward the nucleoplasm and contains a region accessible for site-specific endoproteinase cleavage. In biochemical fractionation, nurim remained extremely tightly bound to nuclear fractions and was released in significant quantities only in the presence of 4 m urea. Under conditions in which nuclear lamins were completely extracted, a significant population of nurim remained resistant to solubilization. This tight binding requires the C-terminal region of the protein. DNase treatment only marginally influenced its retention characteristics in nuclei. Results from consideration of sequence alignments and identification of specific topological features of nurim indicate that it may possess enzymic function. These results are discussed with reference to the retention mechanism and possible nuclear function of nurim.

  5. hnRNP I, the polypyrimidine tract-binding protein: distinct nuclear localization and association with hnRNAs.

    PubMed Central

    Ghetti, A; Piñol-Roma, S; Michael, W M; Morandi, C; Dreyfuss, G

    1992-01-01

    Many hnRNP proteins and snRNPs interact with hnRNA in the nucleus of eukaryotic cells and affect the fate of hnRNA and its processing into mRNA. There are at least 20 abundant proteins in vertebrate cell hnRNP complexes and their structure and arrangement on specific hnRNAs is likely to be important for the processing of pre-mRNAs. hnRNP I, a basic protein of ca. 58,000 daltons by SDS-PAGE, is one of the abundant hnRNA-binding proteins. Monoclonal antibodies to hnRNP I were produced and full length cDNA clones for hnRNP I were isolated and sequenced. The sequence of hnRNP I (59,632 daltons and pI 9.86) demonstrates that it is identical to the previously described polypyrimidine tract-binding protein (PTB) and shows that it is highly related to hnRNP L. The sequences of these two proteins, I and L, define a new family of hnRNP proteins within the large superfamily of the RNP consensus RNA-binding proteins. Here we describe experiments which reveal new and unique properties on the association of hnRNP I/PTB with hnRNP complexes and on its cellular localization. Micrococcal nuclease digestions show that hnRNP I, along with hnRNP S and P, is released from hnRNP complexes by nuclease digestion more readily than most other hnRNP proteins. This nuclease hypersensitivity suggests that hnRNP I is bound to hnRNA regions that are particularly exposed in the complexes. Immunofluorescence microscopy shows that hnRNP I is found in the nucleoplasm but in addition high concentrations are detected in a discrete perinucleolar structure. Thus, the PTB is one of the major proteins that bind pre-mRNAs; it is bound to nuclease-hypersensitive regions of the hnRNA-protein complexes and shows a novel pattern of nuclear localization. Images PMID:1641332

  6. Early nuclear exclusion of the transcription factor max is associated with retinal ganglion cell death independent of caspase activity.

    PubMed

    Petrs-Silva, Hilda; de Freitas, Fabíola G; Linden, Rafael; Chiarini, Luciana B

    2004-02-01

    We examined the behavior of the transcription factor Max during retrograde neuronal degeneration of retinal ganglion cells. Using immunohistochemistry, we found a progressive redistribution of full-length Max from the nucleus to the cytoplasm and dendrites of the ganglion cells following axon damage. Then, the axotomized cells lose all their content of Max, while undergoing nuclear pyknosis and apoptotic cell death. After treatment of retinal explants with either anisomycin or thapsigargin, the rate of nuclear exclusion of Max accompanied the rate of cell death as modulated by either drug. Treatment with a pan-caspase inhibitor abolished both TUNEL staining and immunoreactivity for activated caspase-3, but did not affect the subcellular redistribution of Max immunoreactivity after axotomy. The data show that nuclear exclusion of the transcription factor Max is an early event, which precedes and is independent of the activation of caspases, during apoptotic cell death in the central nervous system.

  7. 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.

  8. 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…

  9. 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)

  10. South Kensington and the Colonies: David Blair of New Zealand and Canada.

    ERIC Educational Resources Information Center

    Chalmers, F. Graeme

    1985-01-01

    The career of art educator David Phillip Blair (1850-1925) is discussed. A graduate from the National Art Training School in South Kensington, London, England, Blair was responsible for introducing the South Kensington art system, with its emphasis on the practical arts, into the schools of New Zealand and Canada. (Author/RM)

  11. 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…

  12. Resident database interfaces to the DAVID system, a heterogeneous distributed database management system

    NASA Technical Reports Server (NTRS)

    Moroh, Marsha

    1988-01-01

    A methodology for building interfaces of resident database management systems to a heterogeneous distributed database management system under development at NASA, the DAVID system, was developed. The feasibility of that methodology was demonstrated by construction of the software necessary to perform the interface task. The interface terminology developed in the course of this research is presented. The work performed and the results are summarized.

  13. 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…

  14. 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

  15. Charles David Keeling and the story of atmospheric CO2 measurements.

    PubMed

    Harris, Daniel C

    2010-10-01

    When he was a postdoc in geochemistry at Caltech, Charles David Keeling found himself ideally prepared for the moment when funding for the International Geophysical Year enabled him to design and build a CO(2) monitoring station on Mauna Loa in Hawaii in 1957. He applied rigorous analytical procedures to a geophysical study with enormous implications for humanity.

  16. Student-Text Interaction: A Modified Replication of David Bloome's Study.

    ERIC Educational Resources Information Center

    Shaw, Karen

    In his ethnographic study of junior high school literacy activities, David Bloome found support for four theoretical constructs of the student-text interaction: (1) education is a process of cultural transmission; (2) reading is defined in terms of the sociocultural context in which it occurs; (3) the interpretation of behavior and of signs occurs…

  17. Proof of George Andrews’s and David Robbins’s q-TSPP conjecture

    PubMed Central

    Koutschan, Christoph; Kauers, Manuel; Zeilberger, Doron

    2011-01-01

    The conjecture that the orbit-counting generating function for totally symmetric plane partitions can be written as an explicit product formula has been stated independently by George Andrews and David Robbins around 1983. We present a proof of this long-standing conjecture.

  18. Critiques of David Elliott's "Music Matters": The Dallas Papers of the MayDay Group.

    ERIC Educational Resources Information Center

    Gates, J. Terry

    2000-01-01

    Introduces a special issue of the "Bulletin of the Council for Research in Music Education." Presents the Dallas (Texas) papers of the MayDay Group, a loosely organized world-wide coalition of music education theorists and practitioners, that critique the book, "Music Matters" (David Elliott). (CMK)

  19. Latino Initiatives: Progress and Challenges. A Report by the Administration of Mayor David N. Dinkins.

    ERIC Educational Resources Information Center

    Medina, Adelita M.

    This annual report for 1990 details initiatives by a select group of New York City (New York) agencies on matters of particular concern to Latinos. New York City's mayor, David Dinkins, originally presented these initiatives in August of 1990 to a meeting of Latino leaders representing diverse agencies and community organization. Highlights of…

  20. 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)

  1. 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…

  2. David Noble's Battle to Defend the 'Sacred Space' of the Classroom.

    ERIC Educational Resources Information Center

    Young, Jeffrey R.

    2000-01-01

    Reports on the crusade of David F. Noble, a history professor at York University (Ontario), against distance education, which he sees as the latest episode in the saga of the corporatization of American higher education. Notes Noble's views on the relationship between politics and technology, intellectual property issues of courseware, and the…

  3. "The Book of Miracles" by David S. Craig and Robert Morgan. Cue Sheet.

    ERIC Educational Resources Information Center

    Pratt, Suzanne

    This performance guide is designed for teachers to use with students before and after a performance of "The Book of Miracles," by David S. Craig and Robert Morgan. The guide, called a "Cuesheet," contains seven activity sheets for use in class, addressing: (1) What Happens in "The Book of Miracles?" (introducing the…

  4. David F. Treagust: congenial soul, science educator, and international research leader

    NASA Astrophysics Data System (ADS)

    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

    2011-09-01

    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 career is his collaborative style that inspires others to produce their best work.

  5. J. David Creswell: Award for Distinguished Scientific Early Career Contributions to Psychology.

    PubMed

    2014-11-01

    APA's Awards for Distinguished Scientific Early Career Contributions to Psychology recognize excellent young psychologists who have not held a doctoral degree for more than nine years. One of the 2014 award winners is J. David Creswell, for "outstanding and innovative research on mechanisms linking stress management strategies to disease." Creswell's award citation, biography, and a selected bibliography are presented here.

  6. 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.

  7. STS-30 Commander David M. Walker during preflight press conference at JSC

    NASA Technical Reports Server (NTRS)

    1989-01-01

    During preflight press conference, STS-30 Commander David M. Walker monitors a question from a news media representative. The event was held in the JSC Auditorium and Public Affairs Facility Bldg 2 briefing room. STS-30 mission will fly onboard Atlantis, Orbiter Vehicle (OV) 104, and is scheduled for an April 28 liftoff.

  8. Kinesthetic Appeals in the Poetic Structures of Contemporary Poetry: The Example of David Wagoner.

    ERIC Educational Resources Information Center

    Miller, Gail

    1987-01-01

    Examines David Wagoner's poetry to illustrate how interpreters can sensitize themselves to a poem's kinesthetic energy by attending to the physical cues of poetic structure such as sound and rhythmic patterns, line lengths and endings, typography, and tensions and resistances. (JD)

  9. 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…

  10. David Bohm and his work-on the occasion of his seventieth birthday

    SciTech Connect

    Jammer, M.

    1988-07-01

    This biographical sketch of David Bohm summarizes his professional career, his relationships with Bohr, Einstein, Pauli, and other quantum theorists of his time, and discusses his published contributions to the fields of quantum mechanics, the refinement of the Schroedinger and Hamilton-Jacobi equations, the notion of hidden variables in particle observation and measure theory, and special relativity theory.

  11. In Support of the Cognitive-Developmental Approach to Moral Education: A Response to David Carr

    ERIC Educational Resources Information Center

    Richmond, Aaron; Cummings, Rhoda

    2004-01-01

    David Carr (2002) has argued against the use of developmental theories as a basis for curriculum development in moral education. Although we find common ground with some aspects of Carr's arguments, we disagree with several of his criticisms of the cognitive-developmental approach to moral education. He confuses romantic ideology (as espoused by…

  12. 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…

  13. Some Thoughts on Censorship and the Teaching of Huckleberry Finn: An Interview with David Bradley.

    ERIC Educational Resources Information Center

    West, Mark I.

    1996-01-01

    Presents an interview with David Bradley, professor of English at Temple University (PA), who defends the teaching of Mark Twain's "Huckleberry Finn" to black students despite recent moves to remove the book from some public school libraries because it is deemed offensive. Bradley provides recommendations for teaching "Huckleberry…

  14. 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.

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

    NASA Astrophysics Data System (ADS)

    Voosen, Paul

    2014-01-01

    It is an honor and privilege to accept the David Perlman Award. Though I have never met Dave, he is a legend, and I can only hope to have a reporting career half as distinguished and a third as long as his own.

  16. Bringing the Social Sciences to Health Policy: An Appreciation of David Mechanic.

    PubMed

    Boyer, Carol A; Gray, Bradford H

    2016-08-01

    David Mechanic has been a pioneering leader in the social and behavioral sciences of health, health services, and health and mental health policy for more than fifty years. One of David's most distinctive qualities has been his vision in identifying trends and defining new research areas and perspectives in health care policy. His early work on how methods of physician payment by capitation and fee-for-service in England and the United States affected physicians' responses to patients and patient care addressed present challenges and many ongoing studies of payment mechanisms. His papers on rationing of health care established a framework for examining alternative allocation mechanisms and just decision making. Influential papers dealt with risk selection, policy challenges in managed care, reducing racial disparities, trust relationships between patients, doctors, and the public and health institutions, and the predicaments of health reform. Focusing on the implementation of the Affordable Care Act, David explored its opportunities and challenges especially in providing comprehensive and effective behavioral health services. A hallmark of his work has been his redirecting our attention to the most severely ill and those in greatest need. Less visible is the leadership and institution building endeavors and the many honors David has received.

  17. Incorporating a Cross-Cultural Perspective in the Undergraduate Psychology Curriculum: An Interview with David Matsumoto.

    ERIC Educational Resources Information Center

    Hill, G. William, IV

    2000-01-01

    Provides an interview with David Matsumoto, Professor of Psychology and Director of the Culture and Emotion Research Laboratory at San Francisco State University. He has studied emotion, human interaction, and culture for more than 15 years. Focuses on cross-cultural psychology and perspectives in relation to the psychology curriculum. (CMK)

  18. 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.…

  19. 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)

  20. Objectivism and Education: A Response to David Elkind's "The Problem with Constructivism"

    ERIC Educational Resources Information Center

    Carson, Jamin

    2005-01-01

    This paper responds to David Elkind's article "The Problem with Constructivism," published in the Summer 2004 issue of The EducationalForum. It argues that Elkind?s thesis?teacher, curricular, and societal readiness lead to the implementation of constructivism?is conceptually problematic. This paper also critiques constructivism and supports…

  1. 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)

  2. 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.

  3. 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…

  4. 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…

  5. 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…

  6. Interview with the editor: David L. Turpin by Robert P. Scholz.

    PubMed

    Turpin, David L

    2010-04-01

    David L. Turpin has worked on dental journals for over 30 years--from his early days on the Pacific Coast Society of Orthodontists Bulletin, to the Angle Orthodontist, and to the American Journal of Orthodontics and Dentofacial Orthopedics. He will retire as editor-in-chief of the American Journal of Orthodontics and Dentofacial Orthopedics at the end of 2010.

  7. 76 FR 39865 - Mr. David Creasey; Notice of Availability of Environmental Assessment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... 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 In accordance with the National Environmental Policy Act of 1969 and the Federal Energy Regulatory...

  8. 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…

  9. 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…

  10. 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…

  11. 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,…

  12. 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…

  13. Astronaut David Scott on slope of Hadley Delta during Apollo 15 EVA

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronaut David R. Scott, mission commander, with tongs and gnomon in hand, studies a boulder on the slope of Hadley Delta during the Apollo 15 lunar surface extravehicular activity. The Lunar Roving Vehicle (LRV) or Rover is in right foreground. View is looking slightly south of west. 'Bennett Hill' is at extreme right. Astronaut James B. Irwin, lunar module pilot, took this photograph.

  14. Astronaut David Scott on slope of Hadley Delta during Apollo 15 EVA

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronaut David R. Scott, mission commander, performs a task at the Lunar Roving Vehicle parked on the edge of Hadley Rille during the first Apollo 15 lunar surface extravehicular activity (EVA-1). This photograph was taken by Astronaut James B. Irwin, lunar module pilot, from the flank of St. George Crater. The view is looking north along the rille.

  15. Astronaut David Scott simulates use of Apollo 15 Lunar Surface Drill at KSC

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronaut David R. Scott, commander of the Apollo 15 lunar landing mission, simulates use of the Apollo 15 Lunar Surface Drill (ALSD) at Kennedy Space Center (KSC), Florida. Scott's fellow moon-exploring crewman, Astronaut James Irwin, can be seen in the background near Lunar Roving Vehicle (LRV) trainer.

  16. Interview with a quality leader: Dr. David Nash. Interviewed by Kathleen Tornow Chai.

    PubMed

    Nash, David B

    2013-01-01

    Dr. David Nash, founder of the original Office of Health Policy in 1990 at Thomas Jefferson University and later the Founding Dean of the Jefferson School of Population Health, is known for his emphasis on measurement and variation in Medical Education. His knowledge and understanding of healthcare policy make this interview timely and relevant.

  17. 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…

  18. 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…

  19. Conflict, Retrenchment, and Reappraisal: The Administration of Higher Education. The David D. Henry Lectures, 1972-78.

    ERIC Educational Resources Information Center

    1979

    The first five David D. Henry lectures, and discussion and response to the first four, are presented in this book. Following a brief introduction by John E. Corbally and a biography of David Dobbs Henry, Clark Kerr's paper, "The Administration of Higher Education in an Era of Change and Conflict" (presented in October, 1972) focuses on…

  20. A Description of the DAVID Interactive Instructional Television System and Its Application to Post High School Education of Deaf.

    ERIC Educational Resources Information Center

    vonFeldt, James R.

    The Digital And Video Interactive Device (DAVID) interactive system was developed at the National Technical Institute for the Deaf in the 1970s for the purpose of enhancing instruction in audiology and speech pathology for deaf students at the postsecondary level. The DAVID system incorporates a minicomputer with a disk drive, a videotape recorder…

  1. 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.

  2. Nuclear Raf-1 kinase regulates the CXCR5 promoter by associating with NFATc3 to drive retinoic acid-induced leukemic cell differentiation.

    PubMed

    Geil, Wendy M; Yen, Andrew

    2014-02-01

    Novel functions of signaling molecules have been revealed in studies of cancer stem cells. Retinoic acid (RA) is an embryonic morphogen and stem cell regulator that controls the differentiation of a patient-derived leukemic cell line, HL-60, which is composed of progenitor cells with bipotent myelo-monocytic differentiation capability. RA treatment of HL-60 cells causes unusually long-lasting mitogen-activated protein kinase signaling, with the cells exhibiting the beginning of G0 cell cycle arrest and functional differentiation by 48 h after treatment with RA. This event coincides with the nuclear translocation of Raf-1, phosphorylated at serine 621. The present study shows how the novel localization of Raf-1 to the nucleus results in transcriptional changes that contribute to the differentiation of HL-60 cells induced by RA. We find that nuclear pS621 Raf-1 associates with NFATc3 near its cognate binding site in the promoter of CXCR5, a gene that must be up-regulated to drive RA-induced differentiation. NFATc3 becomes immunoprecipitable with anti-phosphoserine serum, and CXCR5 is transcriptionally up-regulated upon RA-induced differentiation. Inhibiting the pS621 Raf-1/NFATc3 association with PD98059 inhibits these processes and cripples RA-induced differentiation. In this novel paradigm for Raf-1 and RA function, Raf-1 has a role in driving the nuclear signaling of RA-induced differentiation of leukemic progenitor cells.

  3. 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.

  4. Nuclear localization is required for induction of apoptotic cell death by the Rb-associated p84N5 death domain protein.

    PubMed

    Evans, Randall L; Poe, Bryan S; Goodrich, David W

    2002-07-11

    The mechanisms utilized to transduce apoptotic signals that originate from within the nucleus, in response to DNA damage for example, are not well understood. Identifying these mechanisms is important for predicting how tumor cells will respond to genotoxic radiation or chemotherapy. The Rb tumor suppressor protein can inhibit apoptosis triggered by DNA damage, but how it does so is unclear. We have previously characterized a death domain protein, p84N5, that specifically associates with an amino-terminal domain of Rb protein. The p84N5 death domain is required for its ability to trigger apoptotic cell death. Association with Rb protein inhibits p84N5-induced apoptosis suggesting that it may be a mediator of Rb's effects on apoptosis. Unlike other death domain-containing apoptotic signaling proteins, however, p84N5 is localized predominantly within the nucleus of interphase cells. Here we test whether p84N5 requires nuclear localization in order to trigger apoptosis. We identify the p84N5 nuclear localization signal and demonstrate that nuclear localization is required for p84N5-induced apoptosis. To our knowledge, this identifies p84N5 as the first death-domain containing apoptotic signaling protein that functions within the nucleus. By analogy to other death domain containing proteins, p84N5 may play some role in apoptotic signaling within the nucleus. Further, p84N5 is a potential mediator of Rb protein's effects on DNA damage induced apoptosis.

  5. Britain`s nuclear quandary

    SciTech Connect

    1994-07-01

    This article is review of energy policy in the United Kingdom, in particular, the British government`s review of the nuclear industry. Major topics of this review include: (1) The economic viability of new nuclear stations, (2) The privitization of the nuclear industry, (3) Nuclear waste disposal, and (4) Liabilities associated with decommissioning.

  6. CFD analysis and experimental investigation associated with the design of the Los Alamos nuclear materials storage facility

    SciTech Connect

    Bernardin, J.D.; Hopkins, S.; Gregory, W.S.; Martin, R.A.

    1997-06-01

    The Nuclear Materials Storage Facility (NMSF) at the Los Alamos National Laboratory is being renovated for long-term storage of canisters designed to hold heat-generating nuclear materials, such as powders, ingots, and other components. The continual heat generation within the canisters necessitates a reliable cooling scheme of sufficient magnitude which maintains the stored material temperatures within acceptable limits. The primary goal of this study was to develop both an experimental facility and a computational fluid dynamics (CFD) model of a subsection of the NMSF which could be used to observe general performance trends of a proposed passive cooling scheme and serve as a design tool for canister holding fixtures. Comparisons of numerical temperature and velocity predictions with empirical data indicate that the CFD model provides an accurate representation of the NMSF experimental facility. Minor modifications in the model geometry and boundary conditions are needed to enhance its accuracy, however, the various fluid and thermal models correctly capture the basic physics.

  7. 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.

    2016-11-01

    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.

  8. Modeling of complex wear behavior associated with grid-to-rod fretting in light water nuclear reactors

    SciTech Connect

    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 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.

  9. Modeling of complex wear behavior associated with grid-to-rod fretting in light water nuclear reactors

    DOE PAGES

    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

  10. Cyto-nuclear discordance in the phylogeny of Ficus section Galoglychia and host shifts in plant-pollinator associations

    PubMed Central

    Renoult, Julien P; Kjellberg, Finn; Grout, Cinderella; Santoni, Sylvain; Khadari, Bouchaïb

    2009-01-01

    Background Hybridization events are relatively common in vascular plants. However, the frequency of these events is unevenly distributed across the plant phylogeny. Plant families in which individual species are pollinated by specific pollinator species are predicted to be less prone to hybridization than other families. However, exceptions may occur within these families, when pollinators shift host-plant species. Indeed, host shifts are expected to increase the rate of hybridization events. Pollinators of Ficus section Galoglychia are suspected to have changed host repeatedly, based on several cases of incongruence between plant phylogeny and taxonomy, and insect phylogeny and taxonomy. We tracked cyto-nuclear discordance across section Galoglychia as evidence for hybridization. To achieve a proper global view, we first clarified the monophyly of section Galoglychia as it had been questioned by recent phylogenetic studies. Moreover, we investigated if fig size could be a factor facilitating host shifts. Results Phylogenetic chloroplast and nuclear results demonstrated the monophyly of section Galoglychia. Within section Galoglychia, we detected several cases of statistically significant cyto-nuclear discordance. Discordances concern both terminal nodes of the phylogenetic trees and one deep node defining relationships between subsections. Because nuclear phylogeny is congruent with morphological taxonomy, discordances were caused by the chloroplast phylogeny. Introgressive hybridization was the most likely explanation for these discordances. We also detected that subsections pollinated by several wasp genera had smaller figs and were pollinated by smaller wasps than subsections pollinated by a single wasp genus. Conclusion As hypothesized, we discovered evidences of past hybridization in Ficus section Galoglychia. Further, introgression was only detected in subsections presenting incongruence between plant and pollinator phylogenies and taxonomy. This supports

  11. 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.

  12. Nuclear localization of glutamate-cysteine ligase is associated with proliferation in head and neck squamous cell carcinoma.

    PubMed

    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

    2016-06-01

    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.

  13. Accumulation of nuclear and mitochondrial DNA damage in the frontal cortex cells of patients with HIV-associated neurocognitive disorders.

    PubMed

    Zhang, Yulin; Wang, Meixia; Li, Hongjun; Zhang, Honghai; Shi, Ying; Wei, Feili; Liu, Daojie; Liu, Kai; Chen, Dexi

    2012-06-06

    Oxidative stress has been suggested to play a key role in the neuropathogenesis of HIV infection. HIV proteins (gp120, Tat) and proinflammatory cytokines can trigger the production of reactive oxygen species (ROS), resulting in DNA and RNA lesions. Among all the lesions induced by ROS, one of the most abundant lesions in DNA and RNA is 8-hydroxydeoxyguanosine (8-oxoG). Here, we studied accumulated DNA oxidative damage induced by ROS in the central nervous system (CNS) in tissue from neuro-AIDS patients. The frontal cortex of autopsy tissue from HIV-1 infected patients was adopted for analysis for HIV-1 subtype, nuclear and mitochondrial DNA lesions by immunofluorescence staining, qPCR and sequencing of PCR cloning. This study provides evidence that HIV infection in the CNS leads to nuclear and mitochondrial genomic DNA damage in the brain. High level of nuclear and mtDNA 8-oxoG damage were identified in the cortex autopsy tissue of HAND patients. Increased accumulation of mtDNA mutations and depletion occurs in brain tissue in a subset of HAND cases, and is significantly different from that observed in control cases. These findings suggest that higher level of ROS in the CNS of HAND patients would contribute to the HIV induced neuro-inflammation and apoptosis of neuronal and glial cells.

  14. 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.

  15. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

    PubMed

    Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

    2016-12-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients.

  16. 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

  17. A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria

    PubMed Central

    Nordzieke, Steffen; Zobel, Thomas; Fränzel, Benjamin; Wolters, Dirk A.

    2014-01-01

    Sarcolemmal membrane-associated protein (SLMAP) is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. Further, SLMAP misexpression is associated with endothelial dysfunctions in diabetes and cancer. SLMAP is part of the conserved striatin-interacting phosphatase and kinase (STRIPAK) complex required for specific signaling pathways in yeasts, filamentous fungi, insects, and mammals. In filamentous fungi, STRIPAK was initially discovered in Sordaria macrospora, a model system for fungal differentiation. Here, we functionally characterize the STRIPAK subunit PRO45, a homolog of human SLMAP. We show that PRO45 is required for sexual propagation and cell-to-cell fusion and that its forkhead-associated (FHA) domain is essential for these processes. Protein-protein interaction studies revealed that PRO45 binds to STRIPAK subunits PRO11 and SmMOB3, which are also required for sexual propagation. Superresolution structured-illumination microscopy (SIM) further established that PRO45 localizes to the nuclear envelope, endoplasmic reticulum, and mitochondria. SIM also showed that localization to the nuclear envelope requires STRIPAK subunits PRO11 and PRO22, whereas for mitochondria it does not. Taken together, our study provides important insights into fundamental roles of the fungal SLMAP homolog PRO45 and suggests STRIPAK-related and STRIPAK-unrelated functions. PMID:25527523

  18. Kaposi sarcoma herpes virus latency associated nuclear antigen protein release the G2/M cell cycle blocks by modulating ATM/ATR mediated checkpoint pathway.

    PubMed

    Kumar, Amit; Sahu, Sushil Kumar; Mohanty, Suchitra; Chakrabarti, Sudipta; Maji, Santanu; Reddy, R Rajendra; Jha, Asutosh K; Goswami, Chandan; Kundu, Chanakya N; Rajasubramaniam, Shanmugam; Verma, Subhash C; Choudhuri, Tathagata

    2014-01-01

    The Kaposi's sarcoma-associated herpesvirus infects the human population and maintains latency stage of viral life cycle in a variety of cell types including cells of epithelial, mesenchymal and endothelial origin. The establishment of latent infection by KSHV requires the expression of an unique repertoire of genes among which latency associated nuclear antigen (LANA) plays a critical role in the replication of the viral genome. LANA regulates the transcription of a number of viral and cellular genes essential for the survival of the virus in the host cell. The present study demonstrates the disruption of the host G2/M cell cycle checkpoint regulation as an associated function of LANA. DNA profile of LANA expressing human B-cells demonstrated the ability of this nuclear antigen in relieving the drug (Nocodazole) induced G2/M checkpoint arrest. Caffeine suppressed nocodazole induced G2/M arrest indicating involvement of the ATM/ATR. Notably, we have also shown the direct interaction of LANA with Chk2, the ATM/ATR signalling effector and is responsible for the release of the G2/M cell cycle block.

  19. Comparative analysis of single nucleotide polymorphisms in the nuclear, chloroplast, and mitochondrial genomes in identification of phylogenetic association among seven melon (Cucumis melo L.) cultivars.

    PubMed

    Zhu, Qianglong; Gao, Peng; Liu, Shi; Amanullah, Sikandar; Luan, Feishi

    2016-12-01

    A variety of melons are cultivated worldwide, and their specific biological properties make them an attractive model for molecular studies. This study aimed to investigate the single nucleotide polymorphisms (SNPs) from the mitochondrial, chloroplast, and nuclear genomes of seven melon accessions (Cucumis melo L.) to identify the phylogenetic relationships among melon cultivars with the Illumina HiSeq 2000 platform and bioinformatical analyses. The data showed that there were a total of 658 mitochondrial SNPs (207-295 in each), while there were 0-60 chloroplast SNPs among these seven melon cultivars, compared to the reference genome. Bioinformatical analysis showed that the mitochondrial tree topology was unable to separate the melon features, whereas the maximum parsimony/neighbor joining (MP/NJ) tree of the chloroplast SNPs could define melon features such as seed length, width, thickness, 100-seed weight, and type. SNPs of the nuclear genome were better than the mitochondrial and chloroplast SNPs in the identification of melon features. The data demonstrated the usefulness of mitochondrial, chloroplast, and nuclear SNPs in identification of phylogenetic associations among these seven melon cultivars.

  20. Genomic tagging reveals a random association of endogenous PtdIns5P 4-kinases IIα and IIβ and a partial nuclear localization of the IIα isoform

    PubMed Central

    Wang, Minchuan; Bond, Nicholas J.; Letcher, Andrew J.; Richardson, Jonathan P.; Lilley, Kathryn S.; Irvine, Robin F.; Clarke, Jonathan H.

    2010-01-01

    PtdIns5P 4-kinases IIα and IIβ are cytosolic and nuclear respectively when transfected into cells, including DT40 cells [Richardson, Wang, Clarke, Patel and Irvine (2007) Cell. Signalling 19, 1309–1314]. In the present study we have genomically tagged both type II PtdIns5P 4-kinase isoforms in DT40 cells. Immunoprecipitation of either isoform from tagged cells, followed by MS, revealed that they are associated directly with each other, probably by heterodimerization. We quantified the cellular levels of the type II PtdIns5P 4-kinase mRNAs by real-time quantitative PCR and the absolute amount of each isoform in immunoprecipitates by MS using selective reaction monitoring with 14N,13C-labelled internal standard peptides. The results suggest that the dimerization is complete and random, governed solely by the relative concentrations of the two isoforms. Whereas PtdIns5P 4-kinase IIβ is >95% nuclear, as expected, the distribution of PtdIns4P 4-kinase IIα is 60% cytoplasmic (all bound to membranes) and 40% nuclear. In vitro, PtdIns5P 4-kinase IIα was 2000-fold more active as a PtdIns5P 4-kinase than the IIβ isoform. Overall the results suggest a function of PtdIns5P 4-kinase IIβ may be to target the more active IIα isoform into the nucleus. PMID:20569199

  1. Comparative analysis of single nucleotide polymorphisms in the nuclear, chloroplast, and mitochondrial genomes in identification of phylogenetic association among seven melon (Cucumis melo L.) cultivars

    PubMed Central

    Zhu, Qianglong; Gao, Peng; Liu, Shi; Amanullah, Sikandar; Luan, Feishi

    2016-01-01

    A variety of melons are cultivated worldwide, and their specific biological properties make them an attractive model for molecular studies. This study aimed to investigate the single nucleotide polymorphisms (SNPs) from the mitochondrial, chloroplast, and nuclear genomes of seven melon accessions (Cucumis melo L.) to identify the phylogenetic relationships among melon cultivars with the Illumina HiSeq 2000 platform and bioinformatical analyses. The data showed that there were a total of 658 mitochondrial SNPs (207–295 in each), while there were 0–60 chloroplast SNPs among these seven melon cultivars, compared to the reference genome. Bioinformatical analysis showed that the mitochondrial tree topology was unable to separate the melon features, whereas the maximum parsimony/neighbor joining (MP/NJ) tree of the chloroplast SNPs could define melon features such as seed length, width, thickness, 100-seed weight, and type. SNPs of the nuclear genome were better than the mitochondrial and chloroplast SNPs in the identification of melon features. The data demonstrated the usefulness of mitochondrial, chloroplast, and nuclear SNPs in identification of phylogenetic associations among these seven melon cultivars. PMID:28163587

  2. Hybrid cardiac imaging: SPECT/CT and PET/CT. A joint position statement by the European Association of Nuclear Medicine (EANM), the European Society of Cardiac Radiology (ESCR) and the European Council of Nuclear Cardiology (ECNC).

    PubMed

    Flotats, Albert; Knuuti, Juhani; Gutberlet, Matthias; Marcassa, Claudio; Bengel, Frank M; Kaufmann, Philippe A; Rees, Michael R; Hesse, Birger

    2011-01-01

    Improvements in software and hardware have enabled the integration of dual imaging modalities into hybrid systems, which allow combined acquisition of the different data sets. Integration of positron emission tomography (PET) and computed tomography (CT) scanners into PET/CT systems has shown improvement in the management of patients with cancer over stand-alone acquired CT and PET images. Hybrid cardiac imaging either with single photon emission computed tomography (SPECT) or PET combined with CT depicts cardiac and vascular anatomical abnormalities and their physiologic consequences in a single setting and appears to offer superior information compared with either stand-alone or side-by-side interpretation of the data sets in patients with known or suspected coronary artery disease (CAD). Hybrid systems are also advantageous for the patient because of the single short dual data acquisition. However, hybrid cardiac imaging has also generated controversy with regard to which patients should undergo such integrated examination for clinical effectiveness and minimization of costs and radiation dose, and if software-based fusion of images obtained separately would be a useful alternative. The European Association of Nuclear Medicine (EANM), the European Society of Cardiac Radiology (ESCR) and the European Council of Nuclear Cardiology (ECNC) in this paper want to present a position statement of the institutions on the current roles of SPECT/CT and PET/CT hybrid cardiac imaging in patients with known or suspected CAD.

  3. Direct Self-Assembly of a 2D and 3D Star of David.

    PubMed

    Song, Bo; Zhang, Zhe; Wang, Kun; Hsu, Chih-Hao; Bolarinwa, Olapeju; Wang, Jing; Li, Yiming; Yin, Guang-Qiang; Rivera, Edwin; Yang, Hai-Bo; Liu, Changlin; Xu, Bingqian; Li, Xiaopeng

    2017-04-06

    Two- and three-dimensional metallosupramolecules shaped like a Star of David were synthesized by the self-assembly of a tetratopic pyridyl ligand with a 180° diplatinum(II) motif and Pd(II) ions, respectively. In contrast to other strategies, such as template-directed synthesis and stepwise self-assembly, this design enables the formation of 2D and 3D structures in one step and high yield. The structures were characterized by both one-dimensional ((1) H, (13) C, (31) P) and two-dimensional (COSY, NOESY, DOSY) NMR spectroscopy, ESI-MS, ion-mobility mass spectrometry (IM-MS), AFM, and TEM. The stabilities of the 2D and 3D structures were measured and compared by gradient tandem mass spectrometry (gMS(2) ). The high stability of the 3D Star of David was correlated to its high density of coordination sites (DOCS).

  4. Role of AIP and its homologue the blindness-associated protein AIPL1 in regulating client protein nuclear translocation.

    PubMed

    van der Spuy, J; Cheetham, M E

    2004-08-01

    Mutations in the AIPL1 (aryl hydrocarbon receptor interacting protein-like 1) cause the blinding disease Leber's congenital amaurosis. AIPL1 is a homologue of the AIP. AIP functions as part of a chaperone heterocomplex to facilitate signalling by the AhR and plays an important role in regulating the nuclear translocation of the receptor. We review the evidence for the role of AIP in protein translocation and compare the potential functions of AIPL1 in the translocation of its interacting partner the NEDD8 ultimate buster protein 1.

  5. Apparatus for suppressing formation of vortices in the coolant fluid of a nuclear reactor and associated method

    DOEpatents

    Ekeroth, Douglas E.; Garner, Daniel C.; Hopkins, Ronald J.; Land, John T.

    1993-01-01

    An apparatus and method are provided for suppressing the formation of vortices in circulating coolant fluid of a nuclear reactor. A vortex-suppressing plate having a plurality of openings therein is suspended within the lower plenum of a reactor vessel below and generally parallel to the main core support of the reactor. The plate is positioned so as to intersect vortices which may form in the circulating reactor coolant fluid. The intersection of the plate with such vortices disrupts the rotational flow pattern of the vortices, thereby disrupting the formation thereof.

  6. Apparatus for suppressing formation of vortices in the coolant fluid of a nuclear reactor and associated method

    DOEpatents

    Ekeroth, D.E.; Garner, D.C.; Hopkins, R.J.; Land, J.T.

    1993-11-30

    An apparatus and method are provided for suppressing the formation of vortices in circulating coolant fluid of a nuclear reactor. A vortex-suppressing plate having a plurality of openings therein is suspended within the lower plenum of a reactor vessel below and generally parallel to the main core support of the reactor. The plate is positioned so as to intersect vortices which may form in the circulating reactor coolant fluid. The intersection of the plate with such vortices disrupts the rotational flow pattern of the vortices, thereby disrupting the formation thereof. 3 figures.

  7. PEOPLE IN PHYSICS: David Bohm and the implicate order: a new paradigm for physics teachers

    NASA Astrophysics Data System (ADS)

    Bettany, Laurence

    1998-11-01

    David Bohm (1917-93) was a highly original and individual physicist. His novel ideas and profound intuition extended not only to the physical world but also to the nature of consciousness and society. Bohm regarded science as having become essentially fragmented in its approach to understanding physical reality and sought a more holistic physics based on order, transformation and flowing movement. His notion of an implicate order provides an unusual and exciting challenge for both teachers and students alike.

  8. 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).

  9. 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.

  10. Building Leaders’ Moral Courage to Defeat the King David Syndrome

    DTIC Science & Technology

    2013-03-01

    surface. Confidential mentoring is a core aspect of management growth at Walt Disney . Walt Disney Studios Chairman and Disney Channels Worldwide...death row to mentor prisoners!” What about “I’m going to Disney World ” to enjoy the rewards of my victory? For Coach Gibbs, investing in the lives...Building Leaders’ Moral Courage to Defeat the King David Syndrome It is curious that physical courage should be so common in the world , and

  11. 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...

  12. Apollo 12 crew welcomed aboard U.S.S. Hornet by Rear Admiral Donald David

    NASA Technical Reports Server (NTRS)

    1969-01-01

    Rear Admiral Donald C. David, Commander, Manned Spacecraft Recovery Force, Pacific, welcomes the crew of the Apollo 12 lunar landing mission aboard the U.S.S. Hornet, prime recovery vessel for the mission. A color guard was also on hand for the welcoming ceremonies. Inside the Mobile Quarantine Facility are (left to right) Astronauts Charles Conrad Jr., commander; Richard F. Gordon Jr., command module pilot; and Alan L. Bean, lunar module pilot.

  13. Technical Basis for Flood Protection at Nuclear Power Plants

    DTIC Science & Technology

    2015-07-01

    ER D C/ CH L SR -1 5- 3 Technical Basis for Flood Protection at Nuclear Power Plants Co as ta l a nd H yd ra ul ic s La bo ra to ry...2015 Technical Basis for Flood Protection at Nuclear Power Plants James R. Leech, Loren L. Wehmeyer, David A. Margo, Landris T. Lee, Aaron R. Byrd...39180-6199 ERDC/CHL SR-15-3 ii Abstract Current flood- protection regulatory guidance for nuclear power plants is contained in the Regulatory Guide

  14. 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.

  15. 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.

  16. 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.

  17. Ubiquitin Accumulation on Disease Associated Protein Aggregates Is Correlated with Nuclear Ubiquitin Depletion, Histone De-Ubiquitination and Impaired DNA Damage Response

    PubMed Central

    Ben Yehuda, Adi; Risheq, Marwa; Novoplansky, Ofra; Bersuker, Kirill; Kopito, Ron R.; Goldberg, Michal; Brandeis, Michael

    2017-01-01

    Deposition of ubiquitin conjugates on inclusion bodies composed of protein aggregates is a definitive cytopathological hallmark of neurodegenerative diseases. We show that accumulation of ubiquitin on polyQ IB, associated with Huntington’s disease, is correlated with extensive depletion of nuclear ubiquitin and histone de-ubiquitination. Histone ubiquitination plays major roles in chromatin regulation and DNA repair. Accordingly, we observe that cells expressing IB fail to respond to radiomimetic DNA damage, to induce gamma-H2AX phosphorylation and to recruit 53BP1 to damaged foci. Interestingly ubiquitin depletion, histone de-ubiquitination and impaired DNA damage response are not restricted to PolyQ aggregates and are associated with artificial aggregating luciferase mutants. The longevity of brain neurons depends on their capacity to respond to and repair extensive ongoing DNA damage. Impaired DNA damage response, even modest one, could thus lead to premature neuron aging and mortality. PMID:28052107

  18. 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.

  19. 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)

  20. 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:

  1. 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.

  2. Hmga1 null mouse embryonic fibroblasts display downregulation of spindle assembly checkpoint gene expression associated to nuclear and karyotypic abnormalities

    PubMed Central

    Pierantoni, Giovanna Maria; Conte, Andrea; Rinaldo, Cinzia; Tornincasa, Mara; Gerlini, Raffaele; Valente, Davide; Izzo, Antonella; Fusco, Alfredo

    2016-01-01

    ABSTRACT The High Mobility Group A1 proteins (HMGA1) are nonhistone chromatinic proteins with a critical role in development and cancer. We have recently reported that HMGA1 proteins are able to increase the expression of spindle assembly checkpoint (SAC) genes, thus impairing SAC function and causing chromosomal instability in cancer cells. Moreover, we found a significant correlation between HMGA1 and SAC genes expression in human colon carcinomas. Here, we report that mouse embryonic fibroblasts null for the Hmga1 gene show downregulation of Bub1, Bub1b, Mad2l1 and Ttk SAC genes, and present several features of chromosomal instability, such as nuclear abnormalities, binucleation, micronuclei and karyotypic alterations. Interestingky, also MEFs carrying only one impaired Hmga1 allele present karyotypic alterations. These results indicate that HMGA1 proteins regulate SAC genes expression and, thereby, genomic stability also in embryonic cells. PMID:26889953

  3. 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

  4. 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

  5. Nuclear Medicine.

    ERIC Educational Resources Information Center

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  6. 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.

  7. 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…

  8. 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)

  9. Δ-9,11 modification of glucocorticoids dissociates nuclear factor-κB inhibitory efficacy from glucocorticoid response element-associated side effects.

    PubMed

    Baudy, Andreas R; Reeves, Erica K M; Damsker, Jesse M; Heier, Christopher; Garvin, Lindsay M; Dillingham, Blythe C; McCall, John; Rayavarapu, Sree; Wang, Zuyi; Vandermeulen, Jack H; Sali, Arpana; Jahnke, Vanessa; Duguez, Stephanie; DuBois, Debra; Rose, Mary C; Nagaraju, Kanneboyina; Hoffman, Eric P

    2012-10-01

    Glucocorticoids are standard of care for many inflammatory conditions, but chronic use is associated with a broad array of side effects. This has led to a search for dissociative glucocorticoids--drugs able to retain or improve efficacy associated with transrepression [nuclear factor-κB (NF-κB) inhibition] but with the loss of side effects associated with transactivation (receptor-mediated transcriptional activation through glucocorticoid response element gene promoter elements). We investigated a glucocorticoid derivative with a Δ-9,11 modification as a dissociative steroid. The Δ-9,11 analog showed potent inhibition of tumor necrosis factor-α-induced NF-κB signaling in cell reporter assays, and this transrepression activity was blocked by 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one (RU-486), showing the requirement for the glucocorticoid receptor (GR). The Δ-9,11 analog induced the nuclear translocation of GR but showed the loss of transactivation as assayed by GR-luciferase constructs as well as mRNA profiles of treated cells. The Δ-9,11 analog was tested for efficacy and side effects in two mouse models of muscular dystrophy: mdx (dystrophin deficiency), and SJL (dysferlin deficiency). Daily oral delivery of the Δ-9,11 analog showed a reduction of muscle inflammation and improvements in multiple muscle function assays yet no reductions in body weight or spleen size, suggesting the loss of key side effects. Our data demonstrate that a Δ-9,11 analog dissociates the GR-mediated transcriptional activities from anti-inflammatory activities. Accordingly, Δ-9,11 analogs may hold promise as a source of safer therapeutic agents for chronic inflammatory disorders.

  10. Tests of association for quantitative traits in nuclear families using principal components to correct for population stratification.

    PubMed

    Zhang, Lei; Li, Jian; Pei, Yu-Fang; Liu, Yongjun; Deng, Hong-Wen

    2009-11-01

    Traditional transmission disequilibrium test (TDT) based methods for genetic association analyses are robust to population stratification at the cost of a substantial loss of power. We here describe a novel method for family-based association studies that corrects for population stratification with the use of an extension of principal component analysis (PCA). Specifically, we adopt PCA on unrelated parents in each family. We then infer principal components for children from those for their parents through a TDT-like strategy. Two test statistics within the variance-components model are proposed for association tests. Simulation results show that the proposed tests have correct type I error rates regardless of population stratification, and have greatly improved power over two popular TDT-based methods: QTDT and FBAT. The application to the Genetic Analysis Workshop 16 (GAW16) data sets attests to the feasibility of the proposed method.

  11. Pakistan’s Nuclear Weapons: Proliferation and Security Issues

    DTIC Science & Technology

    2009-07-30

    Fissile Material Report 2007,” International Panel on Fissile Materials http://www.fissilematerials.org/ipfm/site_down/gfmr07.pdf; SIPRI Yearbook 2007...for Foreign and Commonwealth Affairs David Miliband told the Charlie Rose Show December 15, 2008, that Islamabad’s nuclear weapons “are under pretty...Weapons in Pakistan,” Pakistan Security Research Unit Brief Number 22, University of Bradford, November 18, 2007. Available at http

  12. Pakistan’s Nuclear Weapons: Proliferation and Security Issues

    DTIC Science & Technology

    2010-02-04

    Fissile Materials http://www.fissilematerials.org/ipfm/ site_down/gfmr07.pdf; SIPRI Yearbook 2007. The International Panel on Fissile Materials estimates... Commonwealth Affairs David Miliband told the Charlie Rose Show December 15, 2008, that Islamabad’s nuclear weapons “are under pretty close lock and key...Brief Number 22, University of Bradford, November 18, 2007. Available at http://spaces.brad.ac.uk:8080/download/attachments/748

  13. Pakistan’s Nuclear Weapons: Proliferation and Security Issues

    DTIC Science & Technology

    2009-12-09

    International Panel on Fissile Materials http://www.fissilematerials.org/ipfm/ site_down/gfmr07.pdf; SIPRI Yearbook 2007. The International Panel on Fissile...and Commonwealth Affairs David Miliband told the Charlie Rose Show December 15, 2008, that Islamabad’s nuclear weapons “are under pretty close lock...Pakistan,” Pakistan Security Research Unit Brief Number 22, University of Bradford, November 18, 2007. Available at http://spaces.brad.ac.uk:8080

  14. 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

  15. The Associative Changes in Scutellum Nuclear Content and Morphology with Viability Loss of Naturally Aged and Accelerated Aging Wheat (Triticum aestivum) Seeds.

    PubMed

    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.

  16. 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

  17. Nuclear Science References Database

    SciTech Connect

    Pritychenko, B.; Běták, E.; Singh, B.; Totans, J.

    2014-06-15

    The Nuclear Science References (NSR) database together with its associated Web interface, is the world's only comprehensive source of easily accessible low- and intermediate-energy nuclear physics bibliographic information for more than 210,000 articles since the beginning of nuclear science. The weekly-updated NSR database provides essential support for nuclear data evaluation, compilation and research activities. The principles of the database and Web application development and maintenance are described. Examples of nuclear structure, reaction and decay applications are specifically included. The complete NSR database is freely available at the websites of the National Nuclear Data Center (http://www.nndc.bnl.gov/nsr) and the International Atomic Energy Agency (http://www-nds.iaea.org/nsr)

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. STS-107 Mission Specialist David Brown arrives at KSC for TCDT

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- STS-107 Mission Specialist David Brown arrives at KSC to take part in Terminal Countdown Demonstration Test activities, which include a simulated launch countdown. Other crew members are Commander Rick Husband, Pilot William 'Willie' McCool, Payload Commander Michael Anderson, Mission Specialists Kalpana Chawla and Laurel Clark and Payload Specialist Ilan Ramon (the first Israeli astronaut). STS-107 is a mission devoted to research and will include more than 80 experiments that will study Earth and space science, advanced technology development, and astronaut health and safety. Launch is scheduled for Jan. 16, 2003.

  5. 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.

  6. 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.

  7. Connor receives David Perlman Award for Excellence in Science Journalism-News: Citation

    NASA Astrophysics Data System (ADS)

    Duff, Oliver

    2012-01-01

    Steve Connor, science editor of the Independent newspaper of London, received the David Perlman Award for Excellence in Science Journalism-News at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. Connor was honored for his article "Expect more extreme winters thanks to global warming, say scientists," published 24 December 2010 in theIndependent. The article covers a computer modeling study that found that losses in sea ice north of Scandinavia and Russia caused by global warming could paradoxically cause harsh, cold winters in the United Kingdom and elsewhere. The Perlman award is for work published with a deadline pressure of 1 week or less.

  8. Connor receives David Perlman Award for Excellence in Science Journalism-News: Response

    NASA Astrophysics Data System (ADS)

    Connor, Steve

    2012-01-01

    Steve Connor, science editor of the Independent newspaper of London, received the David Perlman Award for Excellence in Science Journalism-News at the AGU Fall Meeting Honors Ceremony, held on 7 December 2011 in San Francisco, Calif. Connor was honored for his article "Expect more extreme winters thanks to global warming, say scientists," published 24 December 2010 in theIndependent. The article covers a computer modeling study that found that losses in sea ice north of Scandinavia and Russia caused by global warming could paradoxically cause harsh, cold winters in the United Kingdom and elsewhere. The Perlman award is for work published with a deadline pressure of 1 week or less.

  9. 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.

  10. Homeostasis and change: A commentary on Homeostatic Theory of Obesity by David Marks

    PubMed Central

    DiClemente, Carlo C; Delahanty, Janine

    2016-01-01

    This commentary on David Marks’ article on the Homeostatic Theory of Obesity and his Circle of Discontent mechanism for maintaining problematic eating behavior and obesity offers a perspective on the promise and potential of this theory. At the same time, we challenge the author to incorporate more of a process perspective into the theory. This would include greater exploration of how individuals enter and exit this hypothesized Circle of Discontent, how these mechanisms lead to obesity rather than other internalizing or externalizing disorders, and how the interactions among key variables differ for males and females and developmental stages. PMID:28070395

  11. 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.

  12. Astronaut David Scott gives salute beside U.S. flag during EVA

    NASA Technical Reports Server (NTRS)

    1971-01-01

    Astronaut David R. Scott, commander, gives a military salute while standing beside the deployed U.S. flag during the Apollo 15 lunar surface extravehicular activity (EVA) at the Hadley-Apennine landing site. The flag was deployed toward the end of EVA-2. The Lunar Module 'Falcon' is partially visible on the right. Hadley Delta in the background rises approximately 4,000 meters (about 13,124 feet) above the plain. The base of the mountain is approximately 5 kilometers (about 3 statute miles) away. This photograph was taken by Astronaut James B. Irwin, Lunar Module pilot.

  13. TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation.

    PubMed

    Pype, S; Declercq, W; Ibrahimi, A; Michiels, C; Van Rietschoten, J G; Dewulf, N; de Boer, M; Vandenabeele, P; Huylebroeck, D; Remacle, J E

    2000-06-16

    CD40 belongs to the tumor necrosis factor (TNF) receptor family. CD40 signaling involves the recruitment of TNF receptor-associated factors (TRAFs) to its cytoplasmic domain. We have identified a novel intracellular CD40-binding protein termed TRAF and TNF receptor-associated protein (TTRAP) that also interacts with TNF-R75 and CD30. The region of the CD40 cytoplasmic domain that is required for TTRAP association overlaps with the TRAF6 recognition motif. Association of TTRAP with CD40 increases profoundly in response to treatment of cells with CD40L. Interestingly, TTRAP also associates with TRAFs, with the highest affinity for TRAF6. In transfected cells, TTRAP inhibits in a dose-dependent manner the transcriptional activation of a nuclear factor-kappaB (NF-kappaB)-dependent reporter mediated by CD40, TNF-R75 or Phorbol 12-myristate 13-acetate (PMA) and to a lesser extent by TRAF2, TRAF6, TNF-alpha, or interleukin-1beta (IL-1beta). TTRAP does not affect stimulation of NF-kappaB induced by overexpression of the NF-kappaB-inducing kinase (NIK), the IkappaB kinase alpha (IKKalpha), or the NF-kappaB subunit P65/RelA, suggesting it acts upstream of the latter proteins. Our results indicate that we have isolated a novel regulatory factor that is involved in signal transduction by distinct members of the TNF receptor family.

  14. Host-associated genetic differentiation in a seed parasitic weevil Rhinusa antirrhini (Coleptera: Curculionidae) revealed by mitochondrial and nuclear sequence data.

    PubMed

    Hernández-Vera, Gerardo; Mitrović, Milana; Jović, Jelena; Tosevski, Ivo; Caldara, Roberto; Gassmann, Andre; Emerson, Brent C

    2010-06-01

    Plant feeding insects and the plants they feed upon represent an ecological association that is thought to be a key factor for the diversification of many plant feeding insects, through differential adaptation to different plant selective pressures. While a number of studies have investigated diversification of plant feeding insects above the species level, relatively less attention has been given to patterns of diversification within species, particularly those that also require plants for oviposition and subsequent larval development. In the case of plant feeding insects that also require plant tissues for the completion of their reproductive cycle through larval development, the divergent selective pressure not only acts on adults, but on the full life history of the insect. Here we focus attention on Rhinusa antirrhini (Curculionidae), a species of weevil broadly distributed across Europe that both feeds on, and oviposits and develops within, species of the plant genus Linaria (Plantaginaceae). Using a combination of mtDNA (COII) and nuclear DNA (EF1-alpha) sequencing and copulation experiments we assess evidence for host associated genetic differentiation within R. antirrhini. We find substantial genetic variation within this species that is best explained by ecological specialisation on different host plant taxa. This genetic differentiation is most pronounced in the mtDNA marker, with patterns of genetic variation at the nuclear marker suggesting incomplete lineage sorting and/or gene flow between different host plant forms of R. antirrhini, whose origin is estimated to date to the mid-Pliocene (3.77 Mya; 2.91-4.80 Mya).

  15. Nuclear Fabrication Consortium

    SciTech Connect

    Levesque, Stephen

    2013-04-05

    This report summarizes the activities undertaken by EWI while under contract from the Department of Energy (DOE) Office of Nuclear Energy (NE) for the management and operation of the Nuclear Fabrication Consortium (NFC). The NFC was established by EWI to independently develop, evaluate, and deploy fabrication approaches and data that support the re-establishment of the U.S. nuclear industry: ensuring that the supply chain will be competitive on a global stage, enabling more cost-effective and reliable nuclear power in a carbon constrained environment. The NFC provided a forum for member original equipment manufactures (OEM), fabricators, manufacturers, and materials suppliers to effectively engage with each other and rebuild the capacity of this supply chain by : Identifying and removing impediments to the implementation of new construction and fabrication techniques and approaches for nuclear equipment, including system components and nuclear plants. Providing and facilitating detailed scientific-based studies on new approaches and technologies that will have positive impacts on the cost of building of nuclear plants. Analyzing and disseminating information about future nuclear fabrication technologies and how they could impact the North American and the International Nuclear Marketplace. Facilitating dialog and initiate alignment among fabricators, owners, trade associations, and government agencies. Supporting industry in helping to create a larger qualified nuclear supplier network. Acting as an unbiased technology resource to evaluate, develop, and demonstrate new manufacturing technologies. Creating welder and inspector training programs to help enable the necessary workforce for the upcoming construction work. Serving as a focal point for technology, policy, and politically interested parties to share ideas and concepts associated with fabrication across the nuclear industry. The report the objectives and summaries of the Nuclear Fabrication Consortium

  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. CA150, a nuclear protein associated with the RNA polymerase II holoenzyme, is involved in Tat-activated human immunodeficiency virus type 1 transcription.

    PubMed Central

    Suñé, C; Hayashi, T; Liu, Y; Lane, W S; Young, R A; Garcia-Blanco, M A

    1997-01-01

    Maximal human immunodeficiency virus type 1 (HIV-1) gene expression requires specific cellular factors in addition to the virus-encoded trans-activator protein Tat and the RNA element TAR. We developed a functional assay, based on transcriptional activation in vitro, to identify these cellular factors. Here, we describe the purification and molecular cloning of CA150, a nuclear protein that is associated with the human RNA polymerase II holoenzyme and is involved in Tat-dependent HIV-1 transcriptional activation. The sequence of CA150 contains an extensive glutamine- and alanine-rich repeat that is found in transcriptional modulators such as GAL11 and SSN6 in Saccharomyces cerevisiae and Zeste in Drosophila melanogaster. Immunodepletion of CA150 abolished Tat trans activation in vitro. Moreover, overexpression of a mutant CA150 protein specifically and dramatically decreased Tat-mediated activation of the HIV-1 promoter in vivo, strongly suggesting a role for CA150 in HIV-1 gene regulation. Immunoprecipitation experiments demonstrated that both CA150 and Tat associate with the RNA polymerase II holoenzyme. Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150. PMID:9315662

  18. Distinct Cytoplasmic and Nuclear Fractions of Drosophila Heterochromatin Protein 1: Their Phosphorylation Levels and Associations with Origin Recognition Complex Proteins

    PubMed Central

    Huang, Da Wei; Fanti, Laura; Pak, Daniel T.S.; Botchan, Michael R.; Pimpinelli, Sergio; Kellum, Rebecca

    1998-01-01

    The distinct structural properties of heterochromatin accommodate a diverse group of vital chromosome functions, yet we have only rudimentary molecular details of its structure. A powerful tool in the analyses of its structure in Drosophila has been a group of mutations that reverse the repressive effect of heterochromatin on the expression of a gene placed next to it ectopically. Several genes from this group are known to encode proteins enriched in heterochromatin. The best characterized of these is the heterochromatin-associated protein, HP1. HP1 has no known DNA-binding activity, hence its incorporation into heterochromatin is likely to be dependent upon other proteins. To examine HP1 interacting proteins, we isolated three distinct oligomeric species of HP1 from the cytoplasm of early Drosophila embryos and analyzed their compositions. The two larger oligomers share two properties with the fraction of HP1 that is most tightly associated with the chromatin of interphase nuclei: an underphosphorylated HP1 isoform profile and an association with subunits of the origin recognition complex (ORC). We also found that HP1 localization into heterochromatin is disrupted in mutants for the ORC2 subunit. These findings support a role for the ORC-containing oligomers in localizing HP1 into Drosophila heterochromatin that is strikingly similar to the role of ORC in recruiting the Sir1 protein to silencing nucleation sites in Saccharomyces cerevisiae. PMID:9679132

  19. 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

  20. 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.