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  1. The 13th Annual Legislative Summit (Washington, DC, 2010). Briefing Papers

    National Indian Education Association, 2010

    2010-01-01

    This volume contains briefing papers presented at the 13th Annual National Indian Education Association (NIEA) Legislative Summit held in Washington, DC. The following papers are included: (1) NIEA Appropriations Priorities for FY11; (2) The President's Budget Request for Fiscal Year 2011 for Native Education; (3) BIE Race to the Top; (4)…

  2. Report from the 13th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Calgary, Alberta; September 8–10, 2011

    Vickers, M.M.; Pasieka, J; Dixon, E; McEwan, S.; McKay, A; Renouf, D.; Schellenberg, D; Ruether, D.

    2012-01-01

    The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8–10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer.

  3. The 13th Annual Meeting of the Translational Research Cancer Centers Consortium (TrC3); Immune Suppression and the Tumor Microenvironment, Columbus, Ohio; March 1–2, 2010

    Lesinski, Gregory B.; Carson, William E.; Repasky, Elizabeth A.; Wei, Weizen; Kalinski, Pawel; Lotze, Michael T; June, Carl H.; Petros, William; Muthusamy, Natarajan; Olencki, Thomas

    2010-01-01

    The Translational Research Cancer Centers Consortium (TrC3) is a cancer immunotherapy network, established to promote biologic therapeutics in the Midwestern and Northeastern regions of The United States. The 13th Annual Meeting of the TrC3 was hosted by The Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and took place at The Blackwell Hotel and Conference Center in Columbus, OH on March 1–2, 2010 (http://www.osuccc.o...

  4. 13th International Symposium on Experimental Robotics

    Dudek, Gregory; Khatib, Oussama; Kumar, Vijay

    2013-01-01

    The International Symposium on Experimental Robotics (ISER) is a series of bi-annual meetings which are organized in a rotating fashion around North America, Europe and Asia/Oceania. The goal of  ISER is to provide a forum for research in robotics that focuses on novelty of theoretical contributions validated by experimental results. The meetings are conceived to bring together, in a small group setting, researchers from around the world who are in the forefront of experimental robotics research. This unique reference presents the latest advances across the various fields of robotics, with ideas that are not only conceived conceptually but also explored experimentally. It collects robotics contributions on the current developments and new directions in the field of experimental robotics, which are based on the papers presented at the 13th ISER held held in Québec City, Canada, at the Fairmont Le Château Frontenac, on June 18-21, 2012. This present thirteenth edition of Experimental Robotics edited by Jayd...

  5. 13th International Conference on Information Technology

    2016-01-01

    This book collects articles presented at the 13th International Conference on Information Technology- New Generations, April, 2016, in Las Vegas, NV USA. It includes over 100 chapters on critical areas of IT including Web Technology, Communications, Security, and Data Mining.

  6. 13th International Conference on Chlamydomonas

    Silflow, Carolyn D. [University of Minnesota

    2014-03-11

    The 13th International Conference on Chlamydomonas (EMBO Workshop on the Cell and Molecular Biology of Chlamydomonas) was held May 27 to June 1, 2008 in Hyeres, France. The conference was the biennial meeting for all researchers studying the green algal systems Chlamydomonas and Volvox. The conference brought together approximately 200 investigators from around the world (North America, Asia, Europe and Australia) representing different fields and disciplines (cell biology, genetics, biochemistry, biophysics, plant physiology, genomics). It provided an opportunity for investigators from different countries to share methodologies and to discuss recent results with a focus on the Chlamydomonas experimental system.

  7. 13th International Symposium on Advanced Materials

    The 13th international symposium on advanced materials (ISAM) was held from september 23-27, 2013, at islamabad, Pakistan. The main theme of this conference was to discuss the ever increasing changes and intricacies that characterize modern industry necessitate a growing demand for technical information on advanced materials. In five day of the symposium, nearly Two hundred and twenty seven contributory and invited papers, comprising of Nineteen technical sessions and two poster sessions were presented. Renowned scientists and researchers from foreign and local institutes have shared their counter parts on the topics of common interest. This symposium provided an ideal opportunity for exchange of information amongst scientists, engineers and researchers from all over pakistan and other countries of the world. (A.B.)

  8. 13th International Conference Intelligent Autonomous Systems

    Michael, Nathan; Berns, Karsten; Yamaguchi, Hiroaki

    2016-01-01

    This book describes the latest research accomplishments, innovations, and visions in the field of robotics as presented at the 13th International Conference on Intelligent Autonomous Systems (IAS), held in Padua in July 2014, by leading researchers, engineers, and practitioners from across the world. The contents amply confirm that robots, machines, and systems are rapidly achieving intelligence and autonomy, mastering more and more capabilities such as mobility and manipulation, sensing and perception, reasoning, and decision making. A wide range of research results and applications are covered, and particular attention is paid to the emerging role of autonomous robots and intelligent systems in industrial production, which reflects their maturity and robustness. The contributions have been selected through a rigorous peer-review process and contain many exciting and visionary ideas that will further galvanize the research community, spurring novel research directions. The series of biennial IAS conferences ...

  9. The 13th Malaysian general election: Uncertainties and expectations

    Moniruzzaman, M

    2013-01-01

    Malaysia held its 13th general election on May 5, 2013 which was a contest between two coalitions, the ruling Barisan Nasional (BN) and the opposition Pakatan Rakyat (PR). The latter’s expectations for an outright win did not materialise. The election results have shown a rather status quo with minor losses and gains for the two coalitions. This study analysed the 13th election and found a number of noticeable trends. The Chinese voters have voted overwhelmingly for the opposition. The politi...

  10. The 13th CAS General Assembly Convenes in Beijing

    2006-01-01

    @@ The 13th General Assembly of CAS was held from June 5 to 8 in Beijing. Top State leaders were present at the joint opening session of the 13th CAS General Assembly and the Eighth General Assembly of the Chinese Academy of Engineering (CAE)held on the morning of June 5 at the Great Hall of the People. Chinese President HU Jintao delivered an important speech at the ceremony. State Councilor CHEN Zhili made a special report about the Framework for the National Long- and Mid-term Plan for S&T Development in China at the joint plenary session of CAS and CAE assemblies on June 6.

  11. Proceedings of the 13th symposium on advanced photon research

    The 13th Symposium on Advanced Photon Research was held at Kansai Photon Science Institute, Japan Atomic Energy Agency (JAEA-KPSI) in Kizugawa-shi, Kyoto on November 15 - 16, 2012. This report consists of invited and contributed papers presented at the oral and poster sessions in the Symposium. (author)

  12. The 13th Malaysian general election: Uncertainties and expectations

    M. Moniruzzaman

    2013-06-01

    Full Text Available Malaysia held its 13th general election on May 5, 2013 which was a contest between two coalitions, the ruling Barisan Nasional (BN and the opposition Pakatan Rakyat (PR. The latter’s expectations for an outright win did not materialise. The election results have shown a rather status quo with minor losses and gains for the two coalitions. This study analysed the 13th election and found a number of noticeable trends. The Chinese voters have voted overwhelmingly for the opposition. The political culture of Malaysia is also shifting toward more participatory type with increased social and economic mobility. The days of one-party dominance in Malaysia are apparently over. The electoral politics in Malaysia might become more polarised along ethnic lines which may require reshuffling of its coalition framework and design.

  13. 13th Workshop on Radiation Monitoring for the International Space Station - Final Program

    The Workshop on Radiation Monitoring for the International Space Station (WRMISS) has been held annually since 1996. The major purpose of WRMISS is to provide a forum for discussion of technical issues concerning radiation dosimetry aboard the International Space Station. This includes discussion of new results, improved instrumentation, detector calibration, and radiation environment and transport models. The goal of WRMISS is to enhance international efforts to provide the best information on the space radiation environment in low-Earth orbit and on the exposure of astronauts and cosmonauts in order to optimize the radiation safety of the ISS crew. During the 13th Annual WRMISS, held in the Institute of Nuclear Physics (Krakow, Poland) on 8-10 September 2008, participants presented 47 lectures

  14. 13th International Conference on Distributed Computing and Artificial Intelligence

    Silvestri, Marcello; González, Sara

    2016-01-01

    The special session Decision Economics (DECON) 2016 is a scientific forum by which to share ideas, projects, researches results, models and experiences associated with the complexity of behavioral decision processes aiming at explaining socio-economic phenomena. DECON 2016 held in the University of Seville, Spain, as part of the 13th International Conference on Distributed Computing and Artificial Intelligence (DCAI) 2016. In the tradition of Herbert A. Simon’s interdisciplinary legacy, this book dedicates itself to the interdisciplinary study of decision-making in the recognition that relevant decision-making takes place in a range of critical subject areas and research fields, including economics, finance, information systems, small and international business, management, operations, and production. Decision-making issues are of crucial importance in economics. Not surprisingly, the study of decision-making has received a growing empirical research efforts in the applied economic literature over the last ...

  15. 13th Czechoslovak seminar on plasma physics and technology

    Of the 32 papers presented at the 13th Czechoslovak Seminar on Plasma Physics and Technology, 20 papers deal with low-temperature plasma and its applications, e.g., in thin film production, plasma chemistry and electric engineering, and with various methods of low-temperature plasma diagnostics. The investigation of hot plasma in tokamaks and stellarators is the topic of 5 papers; the latest experimental results achieved in the Czechoslovak tokamak Castor and the Soviet devices Tuman-2A, FT-1 and L-2 are reported. Five papers are devoted to high-power pulse technology applications, represented by plasma heating studies with Czechoslovak electron accelerator REBEX, the Polish plasma focus experiment PF-20, and high-current accelerators of negative ions developed in the USSR. In the only two theoretical papers, strong Langmuir turbulence and the Alfven current drive are studied. (J.U.)

  16. The Geobiology of Weathering: a 13th Hypothesis

    Schwartzman, David

    2015-01-01

    The magnitude of the biotic enhancement of weathering (BEW) has profound implications for the long-term carbon cycle. The BEW ratio is defined as how much faster the silicate weathering carbon sink is under biotic conditions than under abiotic conditions at the same atmospheric pCO2 level and surface temperature. Thus, a 13th hypothesis should be considered in addition to the 12 outlined by Brantley...(2011) regarding the geobiology of weathering: The BEW factor and its evolution over geological time can be inferred from meta-analysis of empirical and theoretical weathering studies. Estimates of the global magnitude of the BEW are presented, drawing from lab, field, watershed data and models of the long-term carbon cycle, with values ranging from one to two orders of magnitude.

  17. 13th International Conference on X-Ray Lasers

    Gautier, Julien; Ros, David; Zeitoun, Philippe

    2014-01-01

    These proceedings comprise of invited and contributed papers presented at the 13th International Conference on X-Ray Lasers (ICXRL 2012) which was held 11–15 June 2012 in Paris, in the famous Quartier Latin, inside the historical Center of Cordeliers. This conference is part of a continuing series dedicated to recent developments and applications of x-ray lasers and other coherent x-ray sources with attention to supporting technologies and instrumentation. New results in the generation of intense, coherent x-rays and progress towards practical devices and their applications are reported in these proceedings, including areas of research in plasma-based x-ray lasers, 4th generation accelerator-based sources and higher harmonic generation. Recent achievements related to the increase of the repetition rate up to 100 Hz and shorter wavelength collisional plasma-based soft x-ray lasers down to about 7 nm are presented. Seeding the amplifying plasma with a femtosecond high-order harmonic of infrared laser was fore...

  18. PREFACE: 13th IMEKO TC17-TC7 Joint Symposium

    Khan, Sanowar

    2010-04-01

    'Without Measurement No Science, Without Science No Measurement' The 13th IMEKO (International Measurement Confederation) TC1-TC7 Joint Symposium was held at City University London, UK from 1-3 September 2010. For the first time this Symposium also included the involvement of IMEKO Technical Committee 13 (TC13) - Measurements in Biology and Medicine. This brings an added dimension to the Symposium in London since the area of measurement science and technology in biology and medicine is an important and a fast growing one. The Symposium was organized by the City University London (www.city.ac.uk) in collaboration with the Institute of Physics (IOP), UK (www.iop.org). The work of this Symposium is reported in this volume. The scope of the Symposium included the main topics covered by the above Technical Committees - education and training in measurement and instrumentation (TC1), measurement science (TC7) and measurements in biology and medicine. These themes underpinned the strap line of the Symposium, 'Without Measurement No Science, Without Science No Measurement' with the highest number of contributions from the measurement science area. The thematic areas were led by invited presentations from each of the areas by eminent speakers. The Symposium provided a useful forum for experts working in these areas for sharing and exchanging their work and ideas. The Symposium attracted participants from many countries of the world including the United States, Japan, Russia and Ukraine. In total over sixty papers are included in the volume and they are presented under the above three key thematic areas. Each paper was independently peer-reviewed by two reviewers from a distinguished international panel. The organizers of the Symposium, City University London have pioneered the establishment of measurement and instrumentation as an academic discipline in the UK through the work of Professor Ludwik Finkelstein who was for many years Chairman of TC1 and a founding member of TC

  19. PREFACE: 13th International Conference on Liquid and Amorphous Metals

    Popel, Pjotr; Gelchinskii, Boris; Sidorov, Valeriy; Son, Leonid; Sabirzjanov, Alexandre

    2007-06-01

    The state of the art in the field of liquid and amorphous metals and alloys is regularly updated through two series of complementary international conferences, the LAM (Liquid and Amorphous Metals) and the RQ (Rapidly Quenched Materials). The first series of the conferences started as LM-1 in 1966 at Brookhaven for the basic understanding of liquid metals. The subsequent LM conferences were held in Tokyo (1972) and Bristol (1976). The conference was renewed in Grenoble (1980) as a LAM conference including amorphous metals and continued in Los Angeles (1983), Garmisch-Partenkirchen (1986), Kyoto (1989), Vienna (1992), Chicago (1995), Dortmund (1998), Yokohama (2001) and Metz (2004). The conferences are mainly devoted to liquid and amorphous metals and alloys. However, communications on some non-metallic systems such as semi conductors, quasicrystals etc, were accepted as well. The conference tradition strongly encourages the participation of junior researchers and graduate students. The 13th conference of the LAM series was organized in Ekaterinburg, Russia, by the Institute of Metallurgy of the Ural Branch of the Russian Academy of Sciences (IMet UB RAS) and Ural State Pedagogical University (USPU) and held on 8-13 July 2007 under the chairmanship of Professors Pjotr Popel (USPU) and Boris Gelchinskii (IMet UB RAS). There were 242 active and about 60 guest participants from 20 countries who attended the conference. There were no parallel sessions and all oral reports were separated into three groups: invited talks (40 min), full-scale (25 min) and brief (15 min) oral reports. The program included 10 sessions, ranging from purely theoretical subjects to technological application of molten and amorphous alloys. The following sessions took place: A) Electronic structure and transport, magnetic properties; B) Phase transitions; C) Structure; D) Atomic dynamics and transport; E) Thermodynamics; F) Modelling, simulation; G) Surface and interface; H) Mechanical properties

  20. Daegu International Poster Exhibition for Colourful Daegu & the 13th World Championships in Athletics

    McCullagh, Joseph Felix

    2008-01-01

    Design poster, exhibited for the Daegu International Poster Exhibition for Colourful Daegu and the 13th World Championships in Athletics 30th September, 2008 Daegu Culture and Arts Center, Daegu, South Korea

  1. A Discussion of the 13th Dalai Lama during the Period from 1910 to 1912

    LIANG Zhongcui

    2014-01-01

    Following the decline of the Qing dynasty and its weak foreign policy , the Tibetan people became gradually dissatisfied with: ( i ) the Qing local administration ’ s lack of progress;( ii) their succumbing to the force of Britain; and ( iii ) their wantonly selling their local benefits . Especially during the time of the 13th Dalai Lama, this kind of mood of dissatisfaction further deep-ened.In order to maintain the benefits of Tibet, the 13th Dalai Lama tried to submit reports directly to the Qing court , and was eager to get the support from the central government of the Qing dynasty . However , this effort did not reach the central gov-ernment due to the barriers created by the royally appointed minister in Tibet . The British army launched a second invasion of Tibet in 1903, and soon occupied Lhasa.To the 13th Dalai Lama’ s disappointment , Youtai, the royal minister in Ti-bet, did not consider the Tibetan ’ s strong anger about the British invasion , but tried to appease the enemy in order to safeguard “peaceful relations”. And, at the same time he framed the 13th Dalai Lama saying“his abandonment of the land became an excuse for the foreign enemy ’ s invasion”. The Qing court then , without making a detailed investigation , announced a decree that abolished Thubten Gyatso ’ s title of Dalai Lama. Since then , misunderstanding between the 13 th Dalai La-ma and the Qing court deepened further , and some upper-class Tibetans even considered leav-ing the Qing . Taking advantage of the Qing ’ s improper attitude towards the 13th Dalai Lama, Britain began officially to carry out a strategy of winning over the heart of the 13th Dalai Lama. In February, 1910, the 13th Dalai Lama leftLhasa and went into exile in India.Britain wasvery happy about the Dalai ’ s arrival in India.The British man with whom the 13th Dalai Lamahad the most contact during his stay in British Indi -a was Charles Alfred Bell, a political officer ofSikkim.Bell noted the

  2. 13th International Workshop on Condensed Matter Theories

    1990-01-01

    This volume gathers the invited talks of the XIII International Work­ shop on Condensed Matter Theories which took place in Campos do Jordao near Sao Paulo, Brazil, August 6-12, 1989. It contains contributions in a wide variety of fields including neutral quantum and classical fluids, electronic systems, composite materials, plasmas, atoms, molecules and nuclei, and as this year's workshop reflected the natural preoccupation in materials science with its spectacular prospect for mankind, room tempera­ ture super-conductivity. All topics are treated from a common viewpoint: that of many-body physics, whether theoretical or simu1ational. Since the very first workshop, held at the prestigious Instituto de Fisica Teorica in Sao Paulo, and organized by the same organizer of the 1989 workshop, Professor Valdir Casaca Aguilera-Navarro, the meeting has taken place annually six times in Latin America, four in Europe and three in the United States. Its principal objective has been to innitiate and nurture collaborati...

  3. 13th EU-US Transport Task Force Workshop on transport in fusion plasmas

    Connor, J.W.; Fasoli, A.; Hidalgo, C.;

    2009-01-01

    This report summarizes the contributions presented at the 13th EU-US Transport Task Force Workshop on transport in fusion plasmas, held in Copenhagen, Denmark, 1-4 September 2008. There were sessions on core heat and particle transport; core and edge momentum transport; edge and scrape-off-layer ......This report summarizes the contributions presented at the 13th EU-US Transport Task Force Workshop on transport in fusion plasmas, held in Copenhagen, Denmark, 1-4 September 2008. There were sessions on core heat and particle transport; core and edge momentum transport; edge and scrape...

  4. Feasibility of 13th lymph nodes as sentinels for periampullary carcinoma

    白晓枫

    2013-01-01

    Objective To study the feasibility and clinical value of 13th lymph nodes in predicting general lymph nodes metastases for periampullary carcinoma.Methods A total of 77 patients with pathologically confirmed periampullary carcinoma were recruited.And 26 (18 males and 8

  5. Abstracts of 13th International Congress on Plasma Physics (ICPP 2006). Published in 2 volumes

    This report contains the presentation on the 13-th International Congress on Plasma Physics (ICPP 2006). Five main topics are covered: fundamental problems of plasma physics; fusion plasmas; plasmas in astrophysics and space physics; plasmas in applications and technologies; complex plasmas

  6. Proceedings of the 13th annual meeting on upper atmosphere studies by optical methods

    A total of 41 papers were presented under the following session topics: Atmospheric emissions; auroral features and dynamics; auroral pulsations; airglow and atmospheric parameters; atmospheric constituents; instrumentation and data handling; and observation programs. The report presents the full text or abstracts of 31 of the lectures given at the meeting. 25 of the papers are seperate input to the data base from this report

  7. The 13 th Annual Intelligent Ground Vehicle Competition: intelligent ground vehicles created by intelligent teams

    Theisen, Bernard L.

    2005-10-01

    The Intelligent Ground Vehicle Competition (IGVC) is one of three, unmanned systems, student competitions that were founded by the Association for Unmanned Vehicle Systems International (AUVSI) in the 1990s. The IGVC is a multidisciplinary exercise in product realization that challenges college engineering student teams to integrate advanced control theory, machine vision, vehicular electronics, and mobile platform fundamentals to design and build an unmanned system. Teams from around the world focus on developing a suite of dual-use technologies to equip ground vehicles of the future with intelligent driving capabilities. Over the past 13 years, the competition has challenged undergraduate, graduate and Ph.D. students with real world applications in intelligent transportation systems, the military and manufacturing automation. To date, teams from over 50 universities and colleges have participated. This paper describes some of the applications of the technologies required by this competition and discusses the educational benefits. The primary goal of the IGVC is to advance engineering education in intelligent vehicles and related technologies. The employment and professional networking opportunities created for students and industrial sponsors through a series of technical events over the three-day competition are highlighted. Finally, an assessment of the competition based on participant feedback is presented.

  8. Proceedings of the 13th annual meeting of Japanese Society of Radiation Safety Management 2014 Tokushima

    This is the entitled program and proceedings held from December 3rd through 5th of 2014. Focusing on the issues of Fukushima Accident, the sessions including poster, invited/special speeches etc. are education on radiation, radiation measurement, risk communication, dose level evaluation, radioactivity in environment, contamination inspection, decontamination, management of radiation emission equipment and its effective use. (J.P.N)

  9. Females do not have more injury road accidents on Friday the 13th

    Summala Heikki

    2004-11-01

    Full Text Available Abstract Background This study reinvestigated the recent finding that females – but not males – die in traffic accidents on Friday the 13th more often than on other Fridays (Näyhä S: Traffic deaths and superstition on Friday the 13th. Am J Psychiatry 2002, 159: 2110–2111. The current study used matched setting and injury accident data base that is more numerous than fatality data. If such an effect would be caused by impaired psychic and psychomotor functioning due to more frequent anxiety among women, it should also appear in injury crashes. Methods We used the national Finnish road accident database for 1989–2002. To control seasonal variation, 21 Fridays the 13th were compared in a matched design to previous and following Fridays, excluding all holidays, on number of accidents, male/female responsibility for accidents, and the number of dead, injured and overall number of active participants (drivers, pedestrians and bicyclists as a consequence of the accident. Results There were no significant differences in any examined aspect of road injury accidents among the three Fridays, either in females or males. Women were not overrepresented in crashes that occurred on Fridays 13th. Conclusion There is no consistent evidence for females having more road traffic crashes on Fridays the 13th, based on deaths or road accident statistics. However, this does not imply a non-existent effect of superstition related anxiety on accident risk as no exposure-to-risk data are available. People who are anxious of "Black Friday" may stay home, or at least avoid driving a car.

  10. Field Trials of the Prototype Pounder Rig, Uganda, 20th August - 13th November 1999.

    Ball, Peter; Danert, Kerstin

    1999-01-01

    A prototype low-cost drilling rig was imported to Uganda in August 1999 and handed over to Mpigi District Government. Field trials of this machine were undertaken between 20 th August and 13 th November 1999. This work was enabled through a tripartite Memorandum of Understanding between the Cranfield University/DFID Low Cost well Drilling Project, the Directorate of Water Development (DWD) of the Government of Uganda, and the local Government of Mpigi District. A total of fo...

  11. Irradiation experiments of the 13th-15th OGL-1 fuel assemblies

    The Oarai Gas Loop-1, OGL-1, which had been installed in the Japan Materials Testing Reactor (JMTR) of the Oarai Research Establishment of the Japan Atomic Energy Research Institute (JAERI), was an in-pile helium loop for irradiation of high-temperature gas-cooled reactor fuels at high pressure and temperature. This report describes results of fabrication, irradiation and post-irradiation examinations (PIEs) of the 13th-15th OGL-1 fuel assemblies. The 13th and 15th fuel assemblies employed the first-charge fuel of the High Temperature Engineering Test Reactor (HTTR). The 13th assembly was loaded with a high quality fuel, whose as-produced failure fraction had been drastically decreased, compared with that for fuels before that time. The 15th assembly was loaded with a fuel, which had been produced by the same apparatus that was used afterwards for the first charge fuel of the HTTR. Both of these fuel assemblies gave good results in PIEs as well as in the fission-gas release rates during irradiation. The 14th fuel assembly used a trial product of an advanced fuel for high burnup utilization, which employed coated fuel particles (CFPs) with thicker coating layers than those for the first charge fuel. This fuel assembly indicated a spike release of fission gas during irradiation at 1500degC after a transient temperature increase up to this value. As a whole, all of the 13th - 15th assemblies demonstrated good performance of the loaded fuels, giving significantly lower values in fission-gas release rates during irradiation and in failure fractions of CFPs after irradiation, than the corresponding design limit values for the first charge fuel of the HTTR. (author)

  12. Irradiation experiments of the 13th-15th OGL-1 fuel assemblies

    Hayashi, Kimio; Sawa, Kazuhiro; Kitajima, Toshio [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Shiratori, Tetsuo; Kikuchi, Hironobu; Fukuda, Kousaku; Itoh, Tadaharu; Waragai, Heita [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2000-01-01

    The Oarai Gas Loop-1, OGL-1, which had been installed in the Japan Materials Testing Reactor (JMTR) of the Oarai Research Establishment of the Japan Atomic Energy Research Institute (JAERI), was an in-pile helium loop for irradiation of high-temperature gas-cooled reactor fuels at high pressure and temperature. This report describes results of fabrication, irradiation and post-irradiation examinations (PIEs) of the 13th-15th OGL-1 fuel assemblies. The 13th and 15th fuel assemblies employed the first-charge fuel of the High Temperature Engineering Test Reactor (HTTR). The 13th assembly was loaded with a high quality fuel, whose as-produced failure fraction had been drastically decreased, compared with that for fuels before that time. The 15th assembly was loaded with a fuel, which had been produced by the same apparatus that was used afterwards for the first charge fuel of the HTTR. Both of these fuel assemblies gave good results in PIEs as well as in the fission-gas release rates during irradiation. The 14th fuel assembly used a trial product of an advanced fuel for high burnup utilization, which employed coated fuel particles (CFPs) with thicker coating layers than those for the first charge fuel. This fuel assembly indicated a spike release of fission gas during irradiation at 1500degC after a transient temperature increase up to this value. As a whole, all of the 13th - 15th assemblies demonstrated good performance of the loaded fuels, giving significantly lower values in fission-gas release rates during irradiation and in failure fractions of CFPs after irradiation, than the corresponding design limit values for the first charge fuel of the HTTR. (author)

  13. Color-coordinate system from a 13th-century account of rainbows.

    Smithson, Hannah E; Anderson, Philip S; Dinkova-Bruun, Greti; Fosbury, Robert A E; Gasper, Giles E M; Laven, Philip; McLeish, Tom C B; Panti, Cecilia; Tanner, Brian K

    2014-04-01

    We present a new analysis of Robert Grosseteste's account of color in his treatise De iride (On the Rainbow), dating from the early 13th century. The work explores color within the 3D framework set out in Grosseteste's De colore [see J. Opt. Soc. Am. A29, A346 (2012)], but now links the axes of variation to observable properties of rainbows. We combine a modern understanding of the physics of rainbows and of human color perception to resolve the linguistic ambiguities of the medieval text and to interpret Grosseteste's key terms. PMID:24695192

  14. The ultrasonographic diagnosis of fetal encephalocele at 13th gestational week

    Šorak Marija

    2010-01-01

    Full Text Available Background. Encephalocele presents a rare anomaly of central nervous system, developed as a consequence of neural tube closing defect during early embrional development, and it is described by a baggy formation which prolaborates through the pores of the scull, filled with brain tissue, cerebrospinal liquor and entwined with meninges. According to literature search, until this day, the earliest it can be ultrasonically detected is the 13th gestation week, with the appliance of three-dimensional ultrasound. Case report. We presented 25 years old patient, ultrasonically diagnosed with occipital fetal encephalocela at the 13th gestation week. A gestation sack was located in the right uteral corn of the two-corned uterus with one cervix. The diagnosis was confirmed also by trippled value of alpha-fetoprotein in maternal serum: 75,98 IU/mL. Conclusion. Ultrasonic examination is the method of choice for prenatal detection of a fetal anomaly. It is possible to diagnose encephalocele if it prominates above the limits of the scull.

  15. Report of the 13th IEA workshop on radiation effects in ceramic insulators

    The 13th IEA Workshop on Radiation Effects in Ceramic Insulators, based on Annex II: Experimentation on Radiation Damage in Fusion Materials, to the IEA Implementing Agreement for a Programme of Research and Development on Radiation Damage in Fusion Materials, was held on the 9th, December, 2003, at Kyoto International Conference Center, in Kyoto, Japan, in conjunction with the 11th International Conference on Fusion Reactor Materials (ICFRM-11). 44 participants from 10 countries (26 from Japan, 5 from Spain, 3 from Belgium, 3 from USA, 2 from RF, each 1 from Austria, Greece, Italy, Romania, and UK) gathered together and discussed following issues extensively, with the newest experimental results, after the welcome remarks by one of the organizer and chairpersons, Dr. E.R. Hodgson of CIEMAT. Effects of electric field on radiation induced microstructural evolution, parasitic electrical current and voltage induced in cables and wires by radiation effects, optical materials, IFMIF related issues and fundamental aspects were discussed. Significant results such as an observation of γ-alumina and aluminum colloid formation for the Radiation Induced Electrical Degradation mechanism are obtained. This report is workshop summary, abstracts and documents of the 13th IEA Workshop on Radiation Effects in Ceramic Insulators. (author)

  16. 13th International Symposium on Distributed Computing and Artificial Intelligence 2016

    Semalat, Ali; Bocewicz, Grzegorz; Sitek, Paweł; Nielsen, Izabela; García, Julián; Bajo, Javier

    2016-01-01

    The 13th International Symposium on Distributed Computing and Artificial Intelligence 2016 (DCAI 2016) is a forum to present applications of innovative techniques for studying and solving complex problems. The exchange of ideas between scientists and technicians from both the academic and industrial sector is essential to facilitate the development of systems that can meet the ever-increasing demands of today’s society. The present edition brings together past experience, current work and promising future trends associated with distributed computing, artificial intelligence and their application in order to provide efficient solutions to real problems. This symposium is organized by the University of Sevilla (Spain), Osaka Institute of Technology (Japan), and the Universiti Teknologi Malaysia (Malaysia).

  17. The 13th International ICIT Conference Progress in Cryogenics and Isotopes Separation. Proceedings

    The proceedings of the 13th International ICIT Conference Progress in Cryogenics and Isotopes Separation, held in Calimanesti-Caciulata, Romania on 7-9 November 2007 contain plenary lectures (15 lectures) and 8 sections addressing the following subject matters: Section 1. Stable Isotopes Physics. Technologies and Applications (5 papers); Section 2. Cryogenics Technologies and Equipment (9 papers); Section 3. Science and Materials Engineering (17 papers); Section 4. Nuclear Power (22 papers); Section 5. Hydrogen and Fuel Cells (7 papers); Section 6. Environmental Protection. Industrial Risk (24 papers); Section 7. Laboratory Analysis Methods (10 papers); Section 8. Business and Technological Incubator BTI - ICIT RM VALCEA. The proceedings are completed by an Addendum consisting of 5 papers. A number of 45 papers are available in abstract form only and accordingly full text entered the corresponding records

  18. City state institutions under municipal or family rule in 13th-century Alessandria

    Alberto Luongo

    2011-11-01

    Full Text Available In the 13th century many attempts were made to set up personal rule over Alessandria, with varying degrees of success. The first was Manfredi II Lancia, viceroy of Emperor Frederick II. This was followed by Guglielmo VII of Monferrato, whose plans were opposed initially by Oberto Pelavicino and subsequently by Carlo of Angiò. Dominion over Alessandria actively involved the population and the dignitaries of the city (divided by loyalty to the rival Lanzavecchia and Del Pozzo families. They were able to establish or end the rule of one family or another. Hence, the political élite of Alessandria took advantage of the aspirations of foreign rulers to solve internal problems, by according them with different powers as the situation demanded and as the loyalties of the rival factions changed.

  19. Certification of GMP is imperative necessity on radiopharmaceutical manufacturers

    The general circumstances on the conception, quality of GMP and Chinese GMP for radiopharmaceutical manufacturers are introduced briefly. It explains that certification of GMP is imperative necessity on radiopharmaceutical manufacturers

  20. Do-Fluoride "Cryolite By- product Carbon White" Awarded the 13th China Excellent Patent Award%Do-Fluoride "Cryolite By- product Carbon White" Awarded the 13th China Excellent Patent Award

    2011-01-01

    On November 4, the results of the 13th China Patent Awards were publicized by the State Intellectual Property Office of the People's Republic of China. The patent of "production method of cryolite by-product carbon white" declared by Henan Province Jiaozuo Do-Fluoride Company was awarded China Excellent Patent Award.

  1. Proceedings of the 13th meeting for tandem accelerators and related techniques

    The 13th Meeting for Tandem Accelerators and Related Techniques was held on June 8-9, 2000 at Mutsu, Aomori Prefecture, under the auspices of Marine Research Laboratory, Mutsu Establishment, the Japan Atomic Energy Research Institute. About 60 people participated in the meeting from 27 universities and organizations, many of which have a tandem accelerator or an electrostatic accelerator. The objectives of the meeting are to exchange information on tandem accelerates or electrostatic accelerators by making a presentation on related research and topics, and also to enhance mutual friendship of participants, resulting in the contribution to associated R and D. The meeting mainly consisted of presentations by participants and corresponding Q and A; the present situation on facilities of accelerator mass spectrometers (AMS), operations of and research on tandem accelerators or electrostatic accelerators, applications of AMS, related techniques and applications using accelerators, and so on. This report summarizes the contents of presentations made in the meeting. The 30 of the presented papers are indexed individually. (J.P.N.)

  2. The 13th international workshop on targetry and target chemistry proceedings

    This report contains the complete proceedings of the 13th International Workshop on Targetry and Target Chemistry. The Workshop was held at Risoe National Laboratory for Sustainable Energy on July 26-28 2010. The workshop deals with the development of methods and systems for efficient production of radioactive isotopes with accelerators. The WTTC series of workshops was initiated for the purpose of exchanging information about the problems and solutions associated with the production of radioisotopes for biomedical research and their applications to the diagnosis and treatment of disease. The goal of the WTTC is to advance the science associated with radioisotope production targetry. The Workshops are designed to bring experienced targetry scientists together with newcomers to the field, both from industry and academia, to discuss issues of targetry and target chemistry and approaches to exploring in situ target chemistry and the engineering required to optimize production yields. In the workshop, experience, ideas and information are freely and openly shared; learning and collaborations are fostered, with active participation by all attendees. This participation includes both formal and informal sessions. The present proceedings captures both submitted abstracts and the actual presentations showed during the very successful workshop meeting number 13 in the row, the WTTC13. (Author)

  3. Proceedings of the 13th meeting for tandem accelerators and related techniques

    NONE

    2001-02-01

    The 13th Meeting for Tandem Accelerators and Related Techniques was held on June 8-9, 2000 at Mutsu, Aomori Prefecture, under the auspices of Marine Research Laboratory, Mutsu Establishment, the Japan Atomic Energy Research Institute. About 60 people participated in the meeting from 27 universities and organizations, many of which have a tandem accelerator or an electrostatic accelerator. The objectives of the meeting are to exchange information on tandem accelerates or electrostatic accelerators by making a presentation on related research and topics, and also to enhance mutual friendship of participants, resulting in the contribution to associated R and D. The meeting mainly consisted of presentations by participants and corresponding Q and A; the present situation on facilities of accelerator mass spectrometers (AMS), operations of and research on tandem accelerators or electrostatic accelerators, applications of AMS, related techniques and applications using accelerators, and so on. This report summarizes the contents of presentations made in the meeting. The 30 of the presented papers are indexed individually. (J.P.N.)

  4. The 13th international workshop on targetry and target chemistry proceedings

    Haroun, S. (SFU, TRIUMF (Canada)); Givskov, A.; Jensen, Mikael (Technical Univ. of Denmark. Risoe National Laboratory for Sustainable Energy, Radiation Research Division, Roskilde (Denmark))

    2011-06-15

    This report contains the complete proceedings of the 13th International Workshop on Targetry and Target Chemistry. The Workshop was held at Risoe National Laboratory for Sustainable Energy on July 26-28 2010. The workshop deals with the development of methods and systems for efficient production of radioactive isotopes with accelerators. The WTTC series of workshops was initiated for the purpose of exchanging information about the problems and solutions associated with the production of radioisotopes for biomedical research and their applications to the diagnosis and treatment of disease. The goal of the WTTC is to advance the science associated with radioisotope production targetry. The Workshops are designed to bring experienced targetry scientists together with newcomers to the field, both from industry and academia, to discuss issues of targetry and target chemistry and approaches to exploring in situ target chemistry and the engineering required to optimize production yields. In the workshop, experience, ideas and information are freely and openly shared; learning and collaborations are fostered, with active participation by all attendees. This participation includes both formal and informal sessions. The present proceedings captures both submitted abstracts and the actual presentations showed during the very successful workshop meeting number 13 in the row, the WTTC13. (Author)

  5. The Serbo-Bulgarian relations at the end of the 13th century

    Mišić Siniša

    2009-01-01

    Full Text Available Relations between the Serbs and the Bulgarians at the end of the 13th century has been a part of global international relations in the Balkans and in the Danube region. The Tatars (Mongols as the powerful warring people represent external factor that highly influenced those relations. They also made powerful impact on the Serbian and Bulgarian states of the time. The relations between the Serbs and the Bulgarians had not been at the time determined by their attitude toward the Byzantine Empire which was of the Serbian state, while Bulgaria went through tough period of disintegration of the central power. The internal affaires of those two states influenced their mutual relations. During the war with the Byzantine Empire, king Milutin tried to keep Bulgaria on his side, which is the reason why he became related by the marriage to the Bulgarian imperial family. However, strong involvement of Nogay made this alliance non-useful. After 1299 Serbia lost interest for Bulgaria, and behavior toward the queen Ana made two states enter the 14th century as the enemies. The close relations would be maintained with Vidin. In the frame of those relations Milutin's marriage and release of the Bulgarian princess Ana should be regarded, while Stefan's marriage had been motivated differently and happened around 1305/1306.

  6. IAEA technical meeting: 13th meeting of the IFRC Subcommittee on Atomic and Molecular Data for Fusion. Summary report

    This report briefly describes the proceedings, conclusions and recommendations of the 13th Meeting of the Subcommittee on Atomic and Molecular Data for Fusion of the International Fusion Research Council held on 24-25 June, 2002 at the IAEA Headquarters in Vienna Austria. The report includes an Executive Summary of the Subcommittee from this Meeting. (author)

  7. Residual risks of the 13th amendment to the German Atomic Energy Act

    The 13th amendment to the German Atomic Energy Act, which was adopted by the German federal parliament on June 30 and entered into force on August 6, 2011, must be judged in the light of its genesis. Federal Chancellor Merkel, in her government declaration of June 9, 2011, had mentioned topics such as residual risk, safety standards, and risk assumptions, on which the federal government, in the week after the event of March 11, 2011, had commissioned the Advisory Committee on Reactor Safeguards (RSK) to conduct a comprehensive safety review of all German nuclear power plants, and appointed an Ethics Committee to write an opinion on safe energy supply. On the basis of quickly drafted reports, the federal cabinet, without any international harmonization (EU, IEA), adopted a draft opt out law on June 6, 2011. How should the declarations by the Federal Chancellor on June 9, 2011 be classified in terms of atomic energy law? In her words, it all revolved around the residual risk. The debate, which has been shifted to the realm of constitutional law, is open to considerations and steps to attack the new opt out law on grounds of material unconstitutionality (violation of the property guarantee under Sec. 14 or the principle of equality under Art.3 of the Basic Law). As far as final storage is concerned, the amendment to the German Atomic Energy Act announced still for this year, also for transposition of the EURATOM Directive of July 19, 2011 about nuclear waste management, the ''re-assessment of the residual risk'' is not likely to play a role. All these events are reminiscent of a sentence by former Federal Chancellor Schmidt: ''The history of the NATO dual-track decision remains a textbook case showing that even in a democracy emotions using ethical arguments, mixed with demagogy, can become strong enough to cast aside balanced reason.'' There is also a distinction by Max Weber between ''ethics of ideology'' and ''ethics of responsibility''. (orig.)

  8. PREFACE: 13th International Workshop on Slow Positron Beam Techniques and Applications (SLOPOS13)

    2014-04-01

    These proceedings originate from the 13th International Workshop on Slow Positron Beam Techniques and Applications SLOPOS13 which was held at the campus of the Technische Universität München in Garching between 15th-20th September, 2013. This event is part of a series of triennial SLOPOS conferences. In total 123 delegates from 21 countries participated in the SLOPOS13. The excellent scientific program comprised 50 talks and 58 posters presented during two poster sessions. It was very impressive to learn about novel technical developments on positron beam facilities and the wide range of their applications all over the world. The workshop reflected the large variety of positron beam experiments covering fundamental studies, e.g., for efficient production of anti-hydrogen as well as applied research on defects in bulk materials, thin films, surfaces, and interfaces. The topics comprised: . Positron transport and beam technology . Pulsed beams and positron traps . Defect profiling in bulk and layered structures . Nanostructures, porous materials, thin films . Surfaces and interfaces . Positronium formation and emission . Positron interactions with atoms and molecules . Many positrons and anti-hydrogen . Novel experimental techniques The international advisory committee of SLOPOS awarded student prizes for the best presented scientific contributions to a team of students from Finland, France, and the NEPOMUC team at TUM. The conference was overshadowed by the sudden death of Professor Klaus Schreckenbach immediately before the workshop. In commemoration of him as a spiritus rectus of the neutron induced positron source a minutes' silence was hold. We are most grateful for the hard work of the Local Organising Committee, the help of the International Advisory Committee, and all the students for their friendly and efficient support during the meeting. The workshop could not have occurred without the generous support of the Heinz Maier-Leibnitz Zentrum (MLZ), Deutsche

  9. PREFACE: 13th High-Tech Plasma Processes Conference (HTPP-2014)

    2014-11-01

    The High-Tech Plasma Processes - 13th European Plasma Conference (HTPP-2014) was held in Toulouse (France) on 22-27 June 2014. The conference series started in 1990 as a thermal plasma conference and has gradually expanded to include other related topics. Now the High-Tech Plasma Processes - European Plasma Conference (HTPP) is an international conference organised in Europe every two years with topics encompassing the whole field of plasma processing science. The aim of the conference is to bring different scientific communities together, to facilitate contacts between science, technology and industry and to provide a platform for the exploration of both the fundamental topics and new applications of plasmas. For this edition of HTPP, as was the case for the last, we have acheived a well balanced participation from the communities of both thermal and non-thermal plasma researchers. 142 people from 17 countries attended the conference with the total number of contributions being 155, consisting of 8 plenary and 8 invited talks plus 51 oral and 88 poster contributions. We have received numerous papers corresponding to the contributions of HTPP-2014 that have been submitted for publication in this volume of Journal of Physics: Conference Series. Each submitted contribution has been peer reviewed (60 referees with at least two reviewing each paper) and the Editors are very grateful to the referees for their careful support in improving the original manuscripts. In total, 52 manuscripts have been accepted for publication covering a range of topics of plasma processing science from plasma fundamentals to process applications through to experiments, diagnostics and modelling. We have grouped the papers into the following 5 topics: - Arc-Materials Interaction and Metallurgy - Plasma Torches and Spraying - Synthesis of Powders and Nanomaterials - Deposition and Surface Treatment - Non-Equilibrium Plasmas We deeply thank the authors for their enthusiastic and high

  10. Ancient earthen constructions and antiseismic dwellings: Boni's project after the earthquake of 13th January 1915 (Avezzano, Italy)

    E. M. Beranger

    1995-01-01

    After the earthquake of 13th January 1915, the archaeologist Giacomo Boni (1859-1925), inspired by ancient building techniques. proposed the reconstruction of Marsica and the Middle Liri Valley with earthen dwellings. With the cooperation of the Italian Ministry of Agriculture, he organized an exhibition where he collected samples of vegetal trellises which were an essential support to implement these techniques. Furthermore, he rebuilt two huts on the Palatine (Orti Farnesiani): ...

  11. Notarial acts «ad pedes consulum». About some Milanese trial records (12th-13th Century

    Marta Luigina Mangini

    2014-06-01

    Full Text Available Milan’s documentary heritage created between the 12th and the 13th century is to be found by searching the records of the administrative offices and religious institutions that regularly had dealings with it. The aim of this paper is to examine some of these records anew, particularly evaluating the evolution of the constants and variables that have strongly influenced their creation and preservation over time.

  12. Computational Models of Cognitive Processes: Proceedings of the 13th Neural Computation and Psychology Workshop (Ncpw13)

    Mayor, Julien; Gomez, Pablo

    2013-01-01

    Computational Models of Cognitive Processes collects refereed versions of papers presented at the 13th Neural Computation and Psychology Workshop (NCPW13) that took place in July 2012, in San Sebastian (Spain). This workshop series is a well-established and unique forum that brings together researchers from such diverse disciplines as artificial intelligence, cognitive science, computer science, neurobiology, philosophy and psychology to discuss their latest work on models of cognitive proces...

  13. 13th FINA World Championship finals: stroke kinematical and race times according to performance, gender and event

    Jesus, S.; Costa, M. J.; Marinho, D.A.; Garrido, N.; Silva, A. J.; Barbosa, Tiago M.

    2011-01-01

    The aim of this work was to compare the stroke kinematics and race times of the freestyle final races at the 13th FINA World Championships between: (i) the three medalists versus the last three finalists; (ii) males versus female swimmers; (iii) all events in each gender. Data was collected from the champioships official web site. There were no significant differences in the stroke kinematics neither in the race times between medallists and non-medallists. There were significant effects in th...

  14. ARC Code TI: Geometry Manipulation Protocol (GMP)

    National Aeronautics and Space Administration — The Geometry Manipulation Protocol (GMP) is a library which serializes datatypes between XML and ANSI C data structures to support CFD applications. This library...

  15. EDITORIAL: Invited review and topical lectures from the 13th International Congress on Plasma Physics

    Zagorodny, A.; Kocherga, O.

    2007-05-01

    The 13th International Congress on Plasma Physics (ICPP 2006) was organized, on behalf of the International Advisory Committee of the ICPP series, by the National Academy of Sciences of Ukraine and the Bogolyubov Institute for Theoretical Physics (BITP) and held in Kiev, Ukraine, 22 26 May 2006. The Congress Program included the topics: fundamental problems of plasma physics; fusion plasmas; plasmas in astrophysics and space physics; plasmas in applications and technologies; complex plasmas. A total of 305 delegates from 30 countries took part in the Congress. The program included 9 invited review lectures, 32 invited topical and 313 contributed papers (60 of which were selected for oral presentation). The Congress Program was the responsibility of the International Program Committee: Anatoly Zagorodny (Chairman) Bogolyubov Institute for Theoretical Physics, Ukraine Olha Kocherga (Scientific Secretary) Bogolyubov Institute for Theoretical Physics, Ukraine Boris Breizman The University of Texas at Austin, USA Iver Cairns School of Physics, University of Sydney, Australia Tatiana Davydova Institute for Nuclear Research, Ukraine Tony Donne FOM-Institute for Plasma Physics, Rijnhuizen, The Netherlands Nikolai S Erokhin Space Research Institute of RAS, Russia Xavier Garbet CEA, France Valery Godyak OSRAM SYLVANIA, USA Katsumi Ida National Institute for Fusion Science, Japan Alexander Kingsep Russian Research Centre `Kurchatov Institute', Russia E P Kruglyakov Budker Institute of Nuclear Physics, Russia Gregor Morfill Max-Planck-Institut für extraterrestrische Physik, Germany Osamu Motojima National Institute for Fusion Science, Japan Jef Ongena ERM-KMS, Brussels and EFDA-JET, UK Konstantyn Shamrai Institute for Nuclear Research, Ukraine Raghvendra Singh Institute for Plasma Research, India Konstantyn Stepanov Kharkiv Institute of Physics and Technology, Ukraine Masayoshi Tanaka National Institute for Fusion Science, Japan Nodar Tsintsadze Physics Institute, Georgia The

  16. PREFACE: EMAS 2013 Workshop: 13th European Workshop on Modern Developments and Applications in Microbeam Analysis

    Llovet, Xavier, Dr; Matthews, Mr Michael B.; Brisset, François, Dr; Guimarães, Fernanda, Dr; Vieira, Professor Joaquim M., Dr

    2014-03-01

    This volume of the IOP Conference Series: Materials Science and Engineering contains papers from the 13th Workshop of the European Microbeam Analysis Society (EMAS) on Modern Developments and Applications in Microbeam Analysis which took place from the 12th to the 16th of May 2013 in the Centro de Congressos do Alfândega, Porto, Portugal. The primary aim of this series of workshops is to assess the state-of-the-art and reliability of microbeam analysis techniques. The workshops also provide a forum where students and young scientists starting out on a career in microbeam analysis can meet and discuss with the established experts. The workshops have a very specific format comprising invited plenary lectures by internationally recognized experts, poster presentations by the participants and round table discussions on the key topics led by specialists in the field. This workshop was organized in collaboration with LNEG - Laboratório Nacional de Energia e Geologia and SPMICROS - Sociedade Portuguesa de Microscopia. The technical programme included the following topics: electron probe microanalysis, future technologies, electron backscatter diffraction (EBSD), particle analysis, and applications. As at previous workshops there was also a special oral session for young scientists. The best presentation by a young scientist was awarded with an invitation to attend the 2014 Microscopy and Microanalysis meeting at Hartford, Connecticut. The prize went to Shirin Kaboli, of the Department of Metals and Materials Engineering of McGill University (Montréal, Canada), for her talk entitled ''Plastic deformation studies with electron channelling contrast imaging and electron backscattered diffraction''. The continuing relevance of the EMAS workshops and the high regard in which they are held internationally can be seen from the fact that 74 posters from 21 countries were on display at the meeting and that the participants came from as far away as Japan, Canada and the USA. A

  17. PREFACE: 13th General Conference of the Condensed Matter Division of the European Physical Society

    Hoffmann, H.; Klein, R.; Schwoerer, M.

    1993-01-01

    The 13th General Conference of the Condensed Matter Division of the European Physical Society was held in conjunction with the Frühjahrstagung des Arbeitskreises Festkörperphysik der Deutschen Physikalischen Gesellschaft from March 29 till April 2, 1993, in Regensburg. The programme comprised 3,134 contributions : 8 Plenary Talks, 171 Invited Talks, 1,480 Contributed Talks, 1,441 Poster Presentations, 1 Public Evening Talk and 33 Exhibitors Reports. The abstracts have been published as Europhysics Conference Abstracts, Volume 17A/Verhandlungen der Deutschen Physikalischen Gesellschaft 5/1993. The table (see PDF file) shows the distribution of the Plenary and Invited Speakers as well as of the participants according to countries within and outside of Europe. The conference was the largest meeting of physicists held in Germany to date. It was a manifestation of the enormous scientific activity in both basic and applied research in the fields of Condensed Matter Physics in Europe. Most of the research work, which was presented at the conference, was done by young physicists. They represent a large human capital in Europe. Most of the senior physicists and many of our young colleagues maintain scientific cooperations, and also personal friendships, which are and which have been almost independent of national barriers over the past three decades. The latter is to a large extent due to the European Physical Society which always cultivated these contacts, especially between the eastern and western parts of Europe. We would like to express our sincere thanks to the members of the Programme Committee. By their intensive work, which was free from national interests, a scientific programme was prepared, which covered the entire field of Condensed Matter Physics. About 70% of the Plenary and Invited Speakers came from 20 different foreign countries and about 30% from Germany. The meeting therefore has been a truly European Conference. For the young physicists, the number of

  18. Proceedings, 13th International Symposium on Nuclei in the Cosmos (NIC XIII)

    Elekes, Zoltán

    2015-01-01

    Nuclei in the Cosmos is the foremost bi-annual conference of nuclear physicists, astrophysicists, cosmochemists, and others to survey the recent achievements in Nuclear Astrophysics. As an interdisciplinary meeting it promotes mutual understanding and collaboration over fields fundamental to solve a range of open questions, from the origin of the elements to stellar evolution. Inherent part of the conference is a school devoted to students and young scientists where prominent scientists introduce the field of nuclear astrophysics to the participants.

  19. Proceedings of RSEEM 2006 : 13th Research Symposium on Emerging Electronic Markets

    2006-01-01

    Electronic markets have been a prominent topic of research for the past decade. Moreover, we have seen the rise but also the disappearance of many electronic marketplaces in practice. Today, electronic markets are a firm component of inter-organisational exchanges and can be observed in many branches. The Research Symposium on Emerging Electronic Markets is an annual conference bringing together researchers working on various topics concerning electronic markets in research and practice. T...

  20. Direct activation of PDE5 by cGMP

    Mullershausen, Florian; Friebe, Andreas; Feil, Robert; Thompson, W. Joseph; Hofmann, Franz; Koesling, Doris

    2003-01-01

    In platelets, the nitric oxide (NO)–induced cGMP response is indicative of a highly regulated interplay of cGMP formation and cGMP degradation. Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-induced PDE5 phosphorylation. However, we demonstrate that cGMP can directly activate PDE5 without phos...

  1. PREFACE: 13th International Conference on Electrorheological Fluids and Magnetorheological Suspensions (ERMR2012)

    Unal, Halil Ibrahim

    2013-02-01

    Conference photograph The 13th International Conference on Electrorheological Fluids and Magnetorheological Suspensions (ERMR2012) was held in Ankara, Turkey at Gazi University in the Architect Kemaleddin historical hall on 2-6 July 2012. The first International Conference on Electrorheological Fluids and Magnetorheological Suspensions took place nearly 25 years ago and this conference continued the same tradition by providing an arena for researchers around the world to present their new research findings in these fields, and gave them the opportunity to learn about the latest research and technology and to renew their acquaintances. The meeting brought together scientists and engineers in multidisciplinary areas such as chemical engineering, mechanical engineering, materials science and engineering, physics, chemistry and polymer science and technology, to explore the state-of-art technology, identify key areas to be focused on and discuss their problems/issues. All oral presentations were held in a single session to enhance the interactions between the scientists and engineers. The ERMR2012 Conference included plenary lectures given by prominent leaders in their respective fields. About 130 participants from more than 50 organizations attended the conference and 15 plenary speeches, 64 oral presentations and 57 poster presentations took place in the following areas: (i) synthesis, characterization and processing of novel ER/MR materials, (ii) dynamics, chain and structure formation of ER/MR materials, (iii) ER/MR elastomers, ferrogels and their characterizations, (iv) rheological techniques and measurements of ER/MR materials, (v) modeling and simulations of ER/MR materials, (vi) device development and control techniques and (vii) applications of ER/MR materials. The ERMR2012 International Conference began with Turkish classical music performed by the musicians of the Ministry of Culture and Tourism. Rector Professor Dr R Ayhan welcomed the participants and the

  2. 15th International Congress on Plasma Physics & 13th Latin American Workshop on Plasma Physics

    Soto, Leopoldo

    2014-05-01

    The International Advisory Committee of the 15th International Congress on Plasma Physics (ICPP 2010) and the International Advisory Committee of the 13th Latin American Workshop on Plasma Physics (LAWPP 2010), together agreed to carry out this combined meeting ICPP-LAWPP-2010 in Santiago de Chile, 8-13 August 2010, on occasion of the Bicentennial of Chilean Independence. The ICPP-LAWPP-2010 was organized by the Thermonuclear Plasma Department of the Chilean Nuclear Energy Commission (CCHEN) as part of the official program within the framework of the Chilean Bicentennial. The event was also a scientific and academic activity of the project ''Center for Research and Applications in Plasma Physics and Pulsed Power, P4'', supported by National Scientific and Technological Commission, CONICYT-Chile, under grant ACT-26. The International Congress on Plasma Physics was first held in Nagoya, in 1980, and followed by the Congresses: Gothenburg (1982), Lausanne (1984), Kiev (1987), New Delhi (1989), Innsbruck (1992), Foz do Iguacu (1994), Nagoya (1996), Prague (1998), Quebec City (2000), Sydney (2002), Nice (2004), Kiev (2006), and Fukuoka (2008). The purpose of the Congress is to discuss the recent progress and future views in plasma science, including fundamental plasma physics, fusion plasmas, astrophysical plasmas, and plasma applications, and so forth. The Latin American Workshop on Plasma Physics was first held in 1982 in Cambuquira, Brazil, followed by the Workshops: Medellín (1985), Santiago (1988), Buenos Aires (1990), Mexico City (1992), Foz do Iguacu (1994, also combined with ICPP), Caracas (1997), Tandil (1998), La Serena (2000), Sao Pedro (2003), Mexico City (2005), and Caracas (2007). The Latin American Workshop on Plasma Physics is a communication forum of the achievements of the plasma-physics regional community, fostering collaboration between plasma scientists within the region and elsewhere. The program of the ICPP-LAWPP-2010 included the topics

  3. A cracked mirror? - forming the ideal ruler in Epirus and Nicaea in the first half of the 13th century

    Vukašinović Milan

    2015-01-01

    Full Text Available During the first half of the 13th century both Byzantine Empire and the image of its ideal ruler had to undergo a transformation. By applying mostly the narratological analysis to the parenetic texts written in the two successor states of the Empire, the paper sheds light on the dynamic ‘negotiations’ within the Roman elites of the place that the Emperor should have inside the symbolic order, and suggests a possible model of approach to other Byzantine texts and periods. [Projekat Ministarstva nauke Republike Srbije, br. 177015

  4. Proceedings of the 13th China symposium on computer and network applications in modern science and technology

    The 13th China symposium on Computer and Network Applications in Modern Science and Technology was held by Nuclear Electronics and Nuclear Detecting Technology Branch Society on 4-9 November, 2007 in Shenzhen of Guangdong province. 79 articles are collected in the proceedings. The contents include calculation method and software technology, data processing and analysis technique, data acquisition and automatization, network and safety, grid computing technology, information system and database application, system design and development as well as operation maintenance, computer and microprocessor application system and so on.

  5. The Successive CME on 13th; 14th and 15th February 2011 and Forbush decrease on 18 February 2011

    Aims. We analyze the kinematics of three interplanetary coronal mass ejections (ICMEs) that occurred on 13th, 14th and 15th February 2011 in the active region AR 11155 and have shown that they appeared at the Earth orbit on February, 18th and caused Forbush decrease (FD). Methods. The solar coordinates of flares are (S19W03), (S20W14) and (S21W18). The kinematic curves were obtained using STEREO (A and B) data. Additionally, we explore the possibility of the CME-CME interaction for these three events. We compare obtained estimates of ICME arrival with the in-situ measurements from WIND satellite at L1 point and with ground-based cosmic ray data obtained from SEVAN network. Results. The acceleration of each CME is highly correlated with the associated SXR flares energy release. CMEs that erupted at 13 and 14 Feb 2011 are not associated with prominence eruption; maximum velocity was vmax approc. 550 ± 50 km/s and vmax approx. 400 ± 50 km/s, respectively. However, 15 Feb 2011 CME is connected with much more violent eruption associated with a prominence, with maximum velocity of vmax approx. 1400 ± 50 km/s. The last overtakes 13th and 14th Feb CMEs at distances of 32 and 160 R☉, respectively.

  6. Overseas Voter Mobilisation in Singapore: Implications from Malaysia’s 13th General Election

    James Gomez

    2013-01-01

    Full Text Available This paper discusses voter mobilisation and other election-related activities of Malaysian voters living, studying and working in Singapore in the context of Malaysia’s 13th general election (GE13. According to the World Bank, nearly 400,000 Malaysians reside in the city-state. Thus these figures represent a significant Malaysian voter pool based in Singapore. Efforts to mobilise these voters for general elections or other causes have political implications for both countries, which became apparent following Singapore-based Malaysians’ activities to encourage Malaysians to return home to cast their votes during the 13th general election. Singapore’s strict public assembly laws led to several legal issues related to the voter mobilisation and election campaign activities undertaken by Malaysians in the city-state. These legal issues became a source of friction between the two countries during the elections as government leaders and authorities on both sides of the causeway accused the other of interfering in domestic political matters. Given the growing number of Malaysians in Singapore and the likely repeat of Malaysian voter mobilisation activities in Singapore in the run-up to the fourteenth general election (GE14 in 2018, issues related to the election activities of Malaysian voters in Singapore stand to be another set of factors that will shape the health of bilateral relations between these two countries.

  7. 2015 Special Sessions of the 13th International Conference on Practical Applications of Agents and Multi-Agent Systems

    Hernández, Josefa; Mathieu, Philippe; Campbell, Andrew; Fernández-Caballero, Antonio; Moreno, María; Julián, Vicente; Alonso-Betanzos, Amparo; Jiménez-López, María; Botti, Vicente; Trends in Practical Applications of Agents, Multi-Agent Systems and Sustainability : the PAAMS Collection

    2015-01-01

    This volume presents the papers that have been accepted for the 2015 special sessions of the 13th International Conference on Practical Applications of Agents and Multi-Agent Systems, held at University of Salamanca, Spain, at 3rd-5th June, 2015: Agents Behaviours and Artificial Markets (ABAM); Agents and Mobile Devices (AM); Multi-Agent Systems and Ambient Intelligence (MASMAI); Web Mining and Recommender systems (WebMiRes); Learning, Agents and Formal Languages (LAFLang); Agent-based Modeling of Sustainable Behavior and Green Economies (AMSBGE); Emotional Software Agents (SSESA) and Intelligent Educational Systems (SSIES). The volume also includes the paper accepted for the Doctoral Consortium in PAAMS 2015. PAAMS, the International Conference on Practical Applications of Agents and Multi-Agent Systems is an evolution of the International Workshop on Practical Applications of Agents and Multi-Agent Systems. PAAMS is an international yearly tribune to present, to discuss, and to disseminate the latest develo...

  8. Atmospheric CO2 during the 13th century AD: reconciliation of data from ice core measurements and stomatal frequency analysis

    Atmospheric CO2 reconstructions are currently available from direct measurements of air enclosures in Antarctic ice and, alternatively, from stomatal frequency analysis performed on fossil leaves. A period where both methods consistently provide evidence for natural CO2 changes is during the 13th century ad. The results of the two independent methods differ significantly in the amplitude of the estimated CO2 changes (10 ppmv ice versus 34 ppmv stomatal frequency). Here, we compare the stomatal frequency and ice core results by using a firn diffusion model in order to assess the potential influence of smoothing during enclosure on the temporal resolution as well as the amplitude of the CO2 changes. The seemingly large discrepancies between the amplitudes estimated by the contrasting methods diminish when the raw stomatal data are smoothed in an analogous way to the natural smoothing which occurs in the firn

  9. 13th IUPAC International Congress of Pesticide Chemistry: Crop, Environment, and Public Health Protection, Technologies for a Changing World.

    McConnell, Laura L; Racke, Kenneth D; Hapeman, Cathleen J; Seiber, James N

    2016-01-13

    This introductory paper provides an overview of Perspectives papers written by plenary speakers from the 13th IUPAC International Congress of Pesticide Chemistry held in San Francisco, CA, USA, in August 2014. This group of papers emphasizes some of the emerging issues and challenges at the forefront of agricultural research: sustainability; agriculture's response to climate change and population growth; pollinator health and risk assessment; and global food production and food security. In addition, as part of the Congress, a workshop on "Developing Global Leaders for Research, Regulation, and Stewardship of Crop Protection Chemistry in the 21st Century" identified specific recommendations to attract the best scientists to agricultural science, to provide opportunities to study and conduct research on crop protection chemistry topics, and to improve science communication skills. PMID:26709728

  10. Cyclic GMP pathways in hepatic encephalopathy. Neurological and therapeutic implications.

    Montoliu, Carmina; Rodrigo, Regina; Monfort, Pilar; Llansola, Marta; Cauli, Omar; Boix, Jordi; Elmlili, Nisrin; Agusti, Ana; Felipo, Vicente

    2010-03-01

    Cyclic GMP (cGMP) modulates important cerebral processes including some forms of learning and memory. cGMP pathways are strongly altered in hyperammonemia and hepatic encephalopathy (HE). Patients with liver cirrhosis show reduced intracellular cGMP in lymphocytes, increased cGMP in plasma and increased activation of soluble guanylate cyclase by nitric oxide (NO) in lymphocytes, which correlates with minimal HE assessed by psychometric tests. Activation of soluble guanylate cyclase by NO is also increased in cerebral cortex, but reduced in cerebellum, from patients who died with HE. This opposite alteration is reproduced in vivo in rats with chronic hyperammonemia or HE. A main pathway modulating cGMP levels in brain is the glutamate-NO-cGMP pathway. The function of this pathway is impaired both in cerebellum and cortex of rats with hyperammonemia or HE. Impairment of this pathway is responsible for reduced ability to learn some types of tasks. Restoring the pathway and cGMP levels in brain restores learning ability. This may be achieved by administering phosphodiesterase inhibitors (zaprinast, sildenafil), cGMP, anti-inflammatories (ibuprofen) or antagonists of GABAA receptors (bicuculline). These data support that increasing cGMP by safe pharmacological means may be a new therapeutic approach to improve cognitive function in patients with minimal or clinical HE. PMID:20195723

  11. Microbiological criteria for good manufacturing practice (GMP)

    Good manufacturing practice (GMP) consist of an effective manufacturing operation and an effective application of food control. GMP is best supported by the Hazard Analysis Critical Control Point system (HACCP) of the preventive quality assurance, which requires that food irradiation as any food processing technology should be used only with foods of an acceptable quality and adequate handling and storage procedures should precede and follow the processing. The paper concentrates on the first element of the HACCP system for an irradiation plant: the incoming product control, i.e. whether GMP of foods to be irradiated can be assessed by establishing microbiological criteria for their previous good manufacturing practice. In this regard, it summarizes considerations and findings of a ''Consultation on Microbiological Criteria for Foods to be Further Processed Including by Irradiation'' held in 1989 by the International Consultative Group on Food irradiation at the Headquarters of the World Health Organization, Geneva. Difficulties in establishing reference values and defining good manufacturing practices will be pointed out. (orig.)

  12. Microbiological criteria for good manufacturing practice (GMP)

    Farkas, J. (Inst. of Preservation and Livestock Products Technology, Univ. of Horticulture and Food Industry, Budapest (Hungary)); Zukal, E. (Inst. of Preservation and Livestock Products Technology, Univ. of Horticulture and Food Industry, Budapest (Hungary))

    1992-01-01

    Good manufacturing practice (GMP) consist of an effective manufacturing operation and an effective application of food control. GMP is best supported by the Hazard Analysis Critical Control Point system (HACCP) of the preventive quality assurance, which requires that food irradiation as any food processing technology should be used only with foods of an acceptable quality and adequate handling and storage procedures should precede and follow the processing. The paper concentrates on the first element of the HACCP system for an irradiation plant: the incoming product control, i.e. whether GMP of foods to be irradiated can be assessed by establishing microbiological criteria for their previous good manufacturing practice. In this regard, it summarizes considerations and findings of a ''Consultation on Microbiological Criteria for Foods to be Further Processed Including by Irradiation'' held in 1989 by the International Consultative Group on Food irradiation at the Headquarters of the World Health Organization, Geneva. Difficulties in establishing reference values and defining good manufacturing practices will be pointed out. (orig.)

  13. Unusual guanylyl cyclases and cGMP signaling in Dictyostelium discoideum

    Veltman, D.M.; Bosgraaf, L.; van Haastert, P. J. M.

    2004-01-01

    cGMP is used as a second messenger in many eukaryotes. cGMP signaling requires at least three components: Guanylyl cyclases synthesize cGMP from GTP. Specific cGMP-binding proteins propagate the signal, usually by phosphorylation of their target Finally, phosphodiesterases terminate the cGMP signal

  14. Proceedings of the 17th annual day of scientific lectures and 13th annual meeting of the National Society of Black Physicists

    This report contains paper on the following topics: Evaporating Black Holes in an Inflationary Universe; Completely and Partially Polarized Signal Propagation; Is the Jet in Quasar 1038 + 064 Precessing? Physics of the Anisotropic Ferrite Wakefield Accelerator; Absolute Multilayer Characterization at High Spatial Resolution via Real Time Soft X-Ray Imaging; Update on the Status of the Superconducting Supercollider (SSC) Laboratory; The Use of Charge Coupled Devices in Remote Sensing from Space; A Scientific Visit to the USSR; Migdal-Kadanoff Study of Z5 Symmetric Systems with Generalized Action -- Part 1; Migdal-Kadanoff Study of Z5 Symmetric Systems with Generalized Action -- Part 2; and The Voyager Mission Exploration of the Solar System with Robotic Spacecraft

  15. Blue Fluorescent cGMP Sensor for Multiparameter Fluorescence Imaging

    Niino, Yusuke; Hotta, Kohji; Oka, Kotaro

    2010-01-01

    Cyclic GMP (cGMP) regulates many physiological processes by cooperating with the other signaling molecules such as cyclic AMP (cAMP) and Ca2+. Genetically encoded sensors for cGMP have been developed based on fluorescence resonance energy transfer (FRET) between fluorescent proteins. However, to analyze the dynamic relationship among these second messengers, combined use of existing sensors in a single cell is inadequate because of the significant spectral overlaps. A single wavelength indica...

  16. [Chronic disease and health condition prevention in childhood: emphases from the 13th Symposium of Preventive Pediatrics].

    Batinica, Maja; Grgurić, Josip; Jadrijević-Cvrlje, Filip

    2013-01-01

    Chronic diseases in childhood have become an important priority, especially in developed countries, because of higher prevalence, relatively and absolutely. Besides that, inappropriate procedures a chronically ill child can result in child's growth and development disorder. According to literature data, 15-20% of children have chronic disease with the impact on their physical, mental and emotional status. Disease prevention strategies are described at the primary, secondary and tertiary level: how to avoid occurrence of disease, how to diagnose and treat existent disease in early stages, before it causes significant morbidity, and finally how to reduce negative impact of existent disease by restoring function and reducing disease-related complications - how to improve quality of life of children with chronic diseases. The new term of quaternary prevention describes methods to mitigate or avoid results of unnecessary or excessive interventions in the health system. In this paper the authors present recent attitudes about chronic diseases prevention modalities in childhood, which, at the beggining of the 21st century, have become more intriguing and represent a new challenge for pediatric health care. Thus, from preventive standpoint, the following chronic illnesses are discussed: asthma, malignant diseases, autism, epilepsy, cerebral palsy, tuberculosis, diabetes type 1, congenital heart diseases, arterial hypertension, celiac disease, and eating disorders. These emphases are from the 13th Preventive Pediatrics Symposium, which took place in Skrad, June 2nd, 2012. Further activities are planned with the aim of continuation of health care furtherance for children with other chronic illnesses. PMID:23991491

  17. Collaborative networks in the internet of services: 13th IFIP WG 5.5 working conference on virtual enterprises, PRO-VE 2012, Bournemouth, UK, October 2012: proceedings

    L.M. Camarinha-Matos; L. Xu; H. Afsarmanesh

    2012-01-01

    This book constitutes the refereed proceedings of the 13th IFIP WG 5.5 Working Conference on Virtual Enterprises, PRO-VE 2012, held in Bournemouth, UK, in October 2012. The 61 revised papers presented were carefully selected from numerous submissions. They provide a comprehensive overview of identif

  18. Preparation of stable 125I cyclic GMP tyrosine methyl ester suitable for 3',5' cyclic GMP radioimmunoassay by HPLC

    Determination of the concentration of cyclic guanosine monophosphate (cGMP) by radioimmunoassay (RIA) depends upon the availability of suitable radiolabeled tracers and antibody to detect the product. Reverse phase chromatographic techniques can easily separate the reaction products of chloramine-T iodination of succinyl cGMP tyrosine methyl ester. The binding characteristics of the iodination reaction products to anti-cGMP antibody have been determined. Purified succinyl cyclic nucleotide 125I-tyrosine methyl ester binds to cGMP antisera identically as commercially available tracer. The tracer is stable for greater than three months

  19. Specific GMP guidelines for radiopharmaceutical products

    These guidelines are intended to complement those provided in ''Good manufacturing practices for pharmaceutical products'', as well as the GMP for sterile pharmaceutical products. The regulatory procedures necessary to control radiopharmaceutical products are in large part determined by the sources of products and methods of manufacture. Manufacturing procedures within the scope of these guidelines include: preparation of radiopharmaceuticals in hospital radiopharmacies, preparation of radiopharmaceuticals in centralized radiopharmacies, production of radiopharmaceuticals in nuclear centres, institutes or industrial manufacturers, preparation and production of radiopharmaceuticals in Positron Emission Tomography (PET) centres

  20. Sterile devices: A GMP (Good Manufacturing Practices) workshop manual

    Derision, R.; Lower, A.; Bimonte, R.

    1983-05-01

    The manual, which covers GMPs for sterilization processes, presents model procedures and forms as well as a variety of articles and reprints. It is a compilation of GMP materials that small device firms may find useful in understanding how some manufacturers have successfully compiled with the GMP requirements as they apply to the manufacture of sterile devices.

  1. Isolation and Partial Characterization of a Cyclic GMP-Dependent Cyclic GMP-Specific Phosphodiesterase from Dictyostelium discoideum

    Bulgakov, Roman; Haastert, Peter J.M. van

    1983-01-01

    The cellular slime mold, Dictyostelium discoideum, contains at least two classes of phosphodiesterase activity. One class of enzymes hydrolyses cyclic AMP (cAMP) and cyclic GMP (cGMP) with approximately equal rates. Another enzyme, which is less than 5% of the total activity, specifically hydrolyses

  2. Distinct Allostery Induced in the Cyclic GMP-binding, Cyclic GMP-specific Phosphodiesterase (PDE5) by Cyclic GMP, Sildenafil, and Metal Ions*

    Biswas, Kabir H.; Visweswariah, Sandhya S.

    2010-01-01

    The activity of many proteins orchestrating different biological processes is regulated by allostery, where ligand binding at one site alters the function of another site. Allosteric changes can be brought about by either a change in the dynamics of a protein, or alteration in its mean structure. We have investigated the mechanisms of allostery induced by chemically distinct ligands in the cGMP-binding, cGMP-specific phosphodiesterase, PDE5. PDE5 is the target for catalytic site inhibitors, s...

  3. The institutions forming the socioeconomic structure of Turkish private enterprises between the 13th and the 19th centuries

    Mehmet Özbirecikli

    2015-04-01

    principios éticos de la vida empresarial, en esencia, son los mismos. Dentro de este contexto, nos atrevemos a sugerir que las raíces del código ético de la vida empresarial turca se retrotraen en la historia a hace más de 800 años. Además, la similitud entre el funcionamiento presente y pasado indica que el origen de la formación de los aprendices para las empresas turcas tiene, igualmente, más de 800 años de historia.This study investigates three institutions forming the socioeconomic structure of Turkish private enterprises between the 13th and 19th Centuries: Akhism (13th-16th century, the Lonca System (the Guilds (16th-18th century, and the Gedik (Monopoly System (18th-20th century. The study particularly focuses on the social and economic rules, vocational training process, and organizational structure of the said institutions in order to discuss the effects of the socioeconomic structure of Turkish enterprises on economic and social development of private enterprises. The study also struggles to link between the relevant current applications and the applications in the past such as the social rules and vocational training. From economic point of view, both the statist structure of the State and the economic rules of the institutions herein caused private enterprises to remain small, and prevented them from having a competitive environment and having capital accumulation. As a result, enterprises could not benefit from new production techniques and the Turkish enterprise mentality fell behind modern developments On the other hand, although these three systems were completely abolished in the early 20th Century, it is seen that especially traces of the Akhism and Lonca systems have still been surviving. Both the most of rules of Akhism and some of the duties of the board of directors of Lonca such as keeping moral standards of production and trade remind us of professional code of ethics of today's modern business life. In other saying, there was code of

  4. Mobile as a Mainstream – Towards Future Challenges in Mobile Learning. Proceedings of the 13th World Conference on Mobile and Contextual Learning (mLearn 2014)

    Kalz, Marco; Bayyurt, Yasemin; Specht, Marcus

    2014-01-01

    This book constitutes the proceedings of the 13th World Conference on Mobile and Contextual Learning, mLearn 2014, held in Istanbul, Turkey, in November 2014. The 20 revised full papers and 17 short papers presented were carefully reviewed and selected from 65 submissions. The papers are organized in topical sections on technologies and interaction; tablets and ebook readers; learning and teaching inside and outside the classroom; learning design and design implications; evaluation and review...

  5. The cGMP system in irradiated animals

    Changes in the functioning of the cGMP system of the thymocytes and liver of mice subjected to 8 Gy roentgen irradiation were found. Within one hour after irradiation an increase in the cGMP level in thymocytes was noted; two rises in the cGMP concentration in the liver were established, at 0.5 and 24 hours after irradiation. These changes in the cGMP level were correlated to an increase in the guanylate cyclase activities in the thymocytes and liver of the mice subjected to irradiation, and to a lesser extent to changes in the activities of cGMP phosphodiesterase in these tissues. A post-irradiation increase in the rat liver guanylate cyclase activity was also observed. A decrease in cGMP phosphodiesterase activity in the liver of the irradiated mice was followed by a change in the enzymatic kinetics and an increase in cGMP phosphodiesterase thermolability. The post-irradiational rise in guanylate cyclase activity was produced by activation of the enzyme. (orig.)

  6. Multiple Degradation Pathways of Chemoattractant Mediated Cyclic GMP Accumulation in Dictyostelium

    Haastert, Peter J.M. van; Lookeren Campagne, Michiel M. van; Kesbeke, Fanja

    1983-01-01

    Chemoattractants induce a transient accumulation of cGMP levels in Dictyostelium. Intracellular cGMP levels reach a peak at 10 s and prestimulated cGMP levels are recovered at about 30 s. Intracellular and extracellular cGMP levels were detected simultaneously after stimulation of D. lacteum cells w

  7. Opposite effects of different hexachlorocyclohexane (lindane) isomers on cerebellar cyclic GMP: relation of cyclic GMP accumulation to seizure activity

    A number of different depressant and convulsant agents have been shown to alter accumulation of cerebellar cyclic GMP. Since the different hexachlorocyclohexane (HCH) isomers elicit different pharmacological responses in mammals, the authors examined their effects on the accumulation of cerebellar cyclic GMP. Mice received one of the HCH isomers and were sacrificed for determination of cyclic GMP concentrations one hour later. Gamma-HCH increased cyclic GMP while alpha and delta -HCH decreased it. In addition, alpha and delta -HCH prevented the increase in cyclic GMP due to the gamma isomer. Picrotoxin increased cyclic GMP in a manner similar to that of gamma-HCH while strychnine produced only a small increase. All three HCH isomers inhibited the binding of 3H-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse cerebellum. It is concluded the different HCH isomers can have different effects on cerebellar cyclic GMP accumulation and that these effects may mediated through actions at the GABA-A receptor linked chloride channel. 15 references, 1 figure, 3 tables

  8. Dexamethasone-dependent modulation of cyclic GMP synthesis in podocytes.

    Lewko, Barbara; Waszkiewicz, Anna; Maryn, Anna; Gołos, Magdalena; Latawiec, Elżbieta; Daca, Agnieszka; Witkowski, Jacek M; Angielski, Stefan; Stępiński, Jan

    2015-11-01

    Podocytes may be direct target for glucocorticoid therapy in glomerular proteinuric disease. Permeability of podocytes largely depends on their capacity to migrate which involves the contractile apparatus in their foot processes. In this study, we examined the effect of synthetic glucocorticoid dexamethasone (DEX) on the ability of podocytes to produce cyclic guanosine monophosphate (cGMP) in the presence of vasoactive factors, atrial natriuretic peptide (ANP), nitric oxide (NO), and angiotensin II (Ang II). We investigated also the effects of cGMP and DEX on podocyte motility. Primary rat podocytes and immortalized mouse podocytes were pretreated with 1 µM DEX for 4 or 24 h. Glomerular hypertension was mimicked by subjecting the cells to mechanical stress. Total and subcellular cGMP levels were determined in podocytes incubated with 0.1 µM ANP, 1 µM S-nitroso-N-acetyl penicillamine (SNAP), and 1 µM Ang II. Cell motility was estimated by a wound-healing assay. The ANP-dependent production of cGMP increased after 4 h exposition to DEX, but was attenuated after 24 h. Adversely, a 24-h pretreatment with DEX augmented the NO-dependent cGMP synthesis. Ang II suppressed the ANP-dependent cGMP production and the effect was enhanced by DEX in mechanical stress conditions. Mechanical stress reduced total cGMP production in the presence of all stimulators, whereas extracellular to total cGMP ratio increased. 8-Br cGMP enhanced podocyte migration which was accompanied by F-actin disassembly. In the presence of DEX these effects were prevented. We conclude that DEX modulates the production of cGMP in podocytes stimulated with vasoactive factors such as Ang II, ANP, and NO, and the effect is time-dependent. cGMP increases podocyte motility, which is prevented by DEX. This mechanism may account for the antiproteinuric effect of glucocorticoids. PMID:26272337

  9. Urinary cGMP concentrations in severe primary pulmonary hypertension

    M. Bogdan; Humbert, M.; Francoual, J; Claise, C.; Duroux, P.; Simonneau, G; Lindenbaum, A.

    1998-01-01

    BACKGROUND—Prognostic evaluation of patients with primary pulmonary hypertension (PPH) requires right heart catheterisation. The development of accurate non-invasive methods for monitoring these patients remains an important task. Cyclic guanosine monophosphate (cGMP) is an indicator of the action of natriuretic peptides and nitric oxide on target cells. Plasma and urinary cGMP concentrations are raised in patients with congestive heart failure in whom they correlate clos...

  10. Preface: Proceedings of the 13th Conference on Liquid and Amorphous Metals (LAM13) (Ekaterinburg, Russia, 8 14 July 2007)

    Popel, Pjotr; Gelchinskii, Boris; Sidorov, Valeriy

    2008-03-01

    The most recent developments in the field of liquid and amorphous metals and alloys are regularly updated through two complementary international conferences: the liquid and amorphous metals conference (LAM) and the rapidly quenched materials (RQ) conference. The first series of conferences started as LM1 in 1966 at Brookhaven for the basic understanding of liquid metals. The subsequent LM conferences were held in Tokyo (1972) and Bristol (1976). The conference was renewed in Grenoble (1980) as a LAM conference including amorphous metals and continued in Los Angeles (1983), Garmisch-Partenkirchen (1986), Kyoto (1989), Vienna (1992), Chicago (1995), Dortmund (1998), Yokohama (2001) and Metz (2004). The conferences are mainly devoted to liquid and amorphous metals and alloys. However, communications on some non-metallic systems such as semiconductors, quasicrystals etc, are also accepted. The conference tradition strongly encourages participation from junior researchers and graduate students. The 13th conference of the LAM series was organized in Ekaterinburg, Russia, by the Institute of Metallurgy of the Ural Branch of the Russian Academy of Sciences (IMet UB RAS) and the Ural State Pedagogical University (USPU), and held from 8-14 July 2007 under the chairmanship of Professors Pjotr Popel (USPU) and Boris Gelchinskii (IMet UB RAS). Two hundred and forty two active participants and about 60 guest participants from 20 countries attended the conference. There were no parallel sessions and all oral reports were separated into three groups: invited talks (40 min), full-scale oral reports (25 min), and brief oral reports (15 min). The program included ten sessions, ranging from purely theoretical subjects to the technological application of molten and amorphous alloys. The following sessions took place: A: Electronic structure and transport, magnetic properties; B: Phase transitions; C: Structure; D: Atomic dynamics and transport; E: Thermodynamics; F: Modelling

  11. Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension.

    Mergia, Evanthia; Stegbauer, Johannes

    2016-04-01

    Cyclic GMP (cGMP) is a ubiquitous intracellular second messenger that mediates a wide spectrum of physiologic processes in multiple cell types within the cardiovascular and nervous systems. Synthesis of cGMP occurs either by NO-sensitive guanylyl cyclases in response to nitric oxide or by membrane-bound guanylyl cyclases in response to natriuretic peptides and has been shown to regulate blood pressure homeostasis by influencing vascular tone, sympathetic nervous system, and sodium and water handling in the kidney. Several cGMPs degrading phosphodiesterases (PDEs), including PDE1 and PDE5, play an important role in the regulation of cGMP signaling. Recent findings revealed that increased activity of cGMP-hydrolyzing PDEs contribute to the development of hypertension. In this review, we will summarize recent research findings regarding the cGMP/PDE signaling in the vasculature, the central nervous system, and the kidney which are associated with the development and maintenance of hypertension. PMID:27079836

  12. The 13th International Conference on Micro and Nanotechnology for Power Generation and Energy Conversion Applications (PowerMEMS 2013)

    Mitcheson, Paul; Beeby, Steve

    2013-12-01

    It is a pleasure to welcome you to The Royal Society in London and the 13th International Conference on Micro- and Nano-Technology for Power Generation and Energy Conversion Applications, or PowerMEMS 2013. The objective of PowerMEMS 2013 is to catalyse innovation in miniature, micro- and nano-scale technologies for power generation and energy conversion. The conference aims to stimulate the exchange of insights and information, and the development of new ideas in the Power MEMS/NEMS field as well as at the meso-scale. It will allow the attendees to interact and network within our multidisciplinary community that includes professionals from many branches of science and engineering. The technical program is led by four invited speakers covering inductive power transfer, chip scale power sources, thermal energy harvesting and implantable biofuel cells. We received 177 abstracts and following a careful reviewing process by the Technical Program Committee a total of 137 papers were selected for presentation. These have been organised into 16 oral sessions in two parallel streams and two poster sessions that have been augmented by 10 late news papers. The oral and regular poster papers are, for the first time, being published by the Institute of Physics. We have made every effort to make PowerMEMS 2013 the busiest yet and have included for the first time the PowerMEMS School. This two-day school held at Imperial College London covered a wide range of power-MEMS topics including technologies for power generation, power transmission, energy storage, power electronics interfaces and metrology. Registrations for the School exceeded our expectations and it was full by early November. We hope this, and other activities such as the Discussion Panel and the inclusion of late news papers, will make PowerMEMS 2013 a memorable success. We have also reached out to new communities, such as those working in wireless power transfer and RF harvesting to broaden the technology remit of

  13. Biofilms and Cyclic di-GMP (c-di-GMP) Signaling: Lessons from Pseudomonas aeruginosa and Other Bacteria.

    Valentini, Martina; Filloux, Alain

    2016-06-10

    The cyclic di-GMP (c-di-GMP) second messenger represents a signaling system that regulates many bacterial behaviors and is of key importance for driving the lifestyle switch between motile loner cells and biofilm formers. This review provides an up-to-date compendium of c-di-GMP pathways connected to biofilm formation, biofilm-associated motilities, and other functionalities in the ubiquitous and opportunistic human pathogen Pseudomonas aeruginosa This bacterium is frequently adopted as a model organism to study bacterial biofilm formation. Importantly, its versatility and adaptation capabilities are linked with a broad range of complex regulatory networks, including a large set of genes involved in c-di-GMP biosynthesis, degradation, and transmission. PMID:27129226

  14. New GMP Models for Caucasus Region

    Jorjiashvili, N.; Godoladze, T.; Tvaradze, N.; Tumanova, N.

    2014-12-01

    The Caucasus is a region of numerous natural hazards and ensuing disasters. Analysis of the losses due to past disasters indicates those most catastrophic in the region have historically been due to strong earthquakes. Estimation of expected ground motion is a fundamental earthquake hazard assessment. The most commonly used parameter for attenuation relation is peak ground acceleration because this parameter gives useful information for Seismic Hazard Assessment. Thus, many peak ground acceleration attenuation relations have been developed by different authors. However, a few attenuation relations were developed for Caucasus region: Ambraseys et al. (1996,2005) which were based on entire European region and they were not focused locally on Caucasus Region, Smit et.al.(2000) that was based on a small amount of acceleration data that really is not enough. Since 2003 construction of Georgian Digital Seismic Network has started with the help of number of International organizations, Projects and Private companies. In this study new GMP models are obtained based on new data from Georgian seismic network and also from neighboring countries. Estimation of models is obtained by classical, statistical way, regression analysis. Also site ground conditions are considered because the same earthquake recorded at the same distance may cause different damage according to ground conditions. Thus, this parameter is emphasized in the present study. Here it must be mentioned that in previous model which only one was done for Caucasus Region (Smit et. al., 2000) local conditions were not considered. Thus, it is an advantage of models from this study.

  15. The end of the nuclear power generation. On the recommendations of the ethics committee according to the 13th amendment to the Atomic Energy Act

    With the 13th Amendment to the Atomic Energy Act the nuclear consequences of the earthquake disaster in Japan will result in an end to nuclear power generation in Germany. Here, the legislature resorted to unusual methods. For the first time, the legislature received advices from the ''ethics committee reliable energy supply''. This Ethics Commission adopted its recommendations ''on behalf of the Chancellor'' in the period from 4th April to 28th May, 2011. The understanding of this development, its epochal character and speed of decision-making requires an excursion into the economic history and the establishment of nuclear power generation with their legal protection.

  16. Feeds from genetically modified plants (GMP) - Nutritional and safety assessment

    The cultivation of GMP increased worldwide from 1.7 (1996) to about 114 million ha. Currently, soybeans (60), corn (24), cotton (11) and canola (5 % of global GM area) are the most important GMP. They are modified mainly for agronomic traits. Such plants are characterized by so-called input traits (GMP of the first generation) without substantial changes in composition or nutritive value. GMP of the second generation (with output traits) should contain more valuable nutrients (e.g. amino acids, fatty acids, vitamins, enzymes etc.) or less anti-nutritive substances (e.g. mycotoxins, inhibitors, allergens etc.). Nutritional and safety assessment of feeds from GMP is a large challenge for animal nutritionists. The paper reviews feeding trials done with various animal species and categories in many countries. Up to now more than 100 feeding studies with food producing animals were published. Since 1997, 18 studies were performed at the Institute of Animal Nutrition of the FLI to determine the effect of first generation GMP feeds on the nutrition of dairy cows, growing bulls, growing and finishing pigs, laying hens, chickens for finishing, as well as with growing and laying quails. This research was recently summarized. The composition of feeds was analysed, and animal studies were used to assess nutritional qualities, including parameters such as digestibility, feed intake, health and performance of target animal species, and effects on food quality derived from the animals. Reproduction was also considered in generation studies with quails and laying hens. Both chemical analyses and the animal studies reveal no significant differences between GMP feeds and their isogenic counterparts and hence strongly support their substantial equivalence. Our results agree with more than 100 studies published in the literature and reviewed recently. Mycotoxin contamination of some GM-crops is lower than of non-GM, which may be one exception to their substantial equivalence. For

  17. Fluorescence-Based Reporter for Gauging Cyclic Di-GMP Levels in Pseudomonas aeruginosa

    Rybtke, Morten T.; Borlee, Bradley R.; Murakami, Keiji;

    2012-01-01

    of antipathogenic compounds. Here we describe the development of fluorescent monitors that can gauge the cellular level of cyclic di-GMP in P. aeruginosa. We have created cyclic di-GMP level reporters by transcriptionally fusing the cyclic di-GMP-responsive cdrA promoter to genes encoding green fluorescent protein....... We show that the reporter constructs give a fluorescent readout of the intracellular level of cyclic di-GMP in P. aeruginosa strains with different levels of cyclic di-GMP. Furthermore, we show that the reporters are able to detect increased turnover of cyclic di-GMP mediated by treatment of P...

  18. JOOSE, N. Peeter (Leiden - Boston, 2004), A Syriac Encyclopaedia of Aristotelian Philosophy: Barhebraeus (13th c.), Butyrum sapientiae, Books of Ethics, Economy and Politics. A Critical Edition, with Introduction, Translation, Commentary and Glossaries

    Monferrer-Sala, J.P.

    2010-01-01

    Reseña de: A Syriac Encyclopaedia of Aristotelian Philosophy: Barhebraeus (13th c.), Butyrum sapientiae, Books of Ethics, Economy and Politics. A Critical Edition, with Introduction, Translation, Commentary and Glossaries

  19. Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy

    Lobatto, Mark E.; Calcagno, Claudia; Otten, Maarten J.; Millon, Antoine; Ramachandran, Sarayu; Paridaans, Maarten P M; van der Valk, Fleur M.; Storm, G; Stroes, Erik S G; Fayad, Zahi A.; Mulder, Willem J M; Metselaar, Josbert M.

    2015-01-01

    The present study describes the development of a good manufacturing practice (GMP)-grade liposomal nanotherapy containing prednisolone phosphate for the treatment of inflammatory diseases. After formulation design, GMP production was commenced which yielded consistent, stable liposomes sized 100. nm

  20. Pharmaceutical development and preclinical evaluation of a GMP-grade anti-inflammatory nanotherapy

    Lobatto, Mark E.; Calcagno, Claudia; Otten, Maarten J.; Millon, Antoine; Ramachandran, Sarayu; Paridaans, Maarten P.M.; Valk, van der Fleur M.; Storm, Gert; Stroes, Erik S.G.; Fayad, Zahi A.; Mulder, Willem J.M.; Metselaar, Josbert M.

    2015-01-01

    The present study describes the development of a good manufacturing practice (GMP)-grade liposomal nanotherapy containing prednisolone phosphate for the treatment of inflammatory diseases. After formulation design, GMP production was commenced which yielded consistent, stable liposomes sized 100 nm

  1. C-di-GMP regulates antimicrobial peptide resistance in Pseudomonas aeruginosa

    Chua, Song Lin; Tan, Sean Yang-Yi; Rybtke, Morten Theil;

    2013-01-01

    Bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) is an intracellular second messenger which controls the life styles of many bacteria. A high intracellular level of c-di-GMP induces a biofilm lifestyle, whereas a low intracellular level of c-di-GMP stimulates dispersal of biofilms and promotes a plankto...... current dogma stating that dispersed cells are inevitably more susceptible to antibiotics than their sessile counterparts....

  2. Responses to Elevated c-di-GMP Levels in Mutualistic and Pathogenic Plant-Interacting Bacteria

    Pérez-Mendoza, Daniel; Aragón, Isabel M.; Prada-Ramírez, Harold A.; Romero-Jiménez, Lorena; Ramos, Cayo; Gallegos, María-Trinidad; Sanjuán, Juan

    2014-01-01

    Despite a recent burst of research, knowledge on c-di-GMP signaling pathways remains largely fragmentary and molecular mechanisms of regulation and even c-di-GMP targets are yet unknown for most bacteria. Besides genomics or bioinformatics, accompanying alternative approaches are necessary to reveal c-di-GMP regulation in bacteria with complex lifestyles. We have approached this study by artificially altering the c-di-GMP economy of diverse pathogenic and mutualistic plant-interacting bacteri...

  3. 76 FR 51395 - Draft Environmental Impact Statement for the General Management Plan (DEIS/GMP), Canaveral...

    2011-08-18

    ... National Park Service Draft Environmental Impact Statement for the General Management Plan (DEIS/GMP... Draft Environmental Impact Statement for the General Management Plan (DEIS/GMP), Canaveral National... 1969 the NPS announces the availability of a DEIS/GMP for Canaveral National Seashore, Florida....

  4. cGMP is tightly bound to bovine retinal rod phosphodiesterase

    Although the total concentration of cGMP in rod outer segments is thought to be substantially greater than the free concentration, no quantitatively relevant site for the bound cGMP has been described in mammalian photoreceptors. They have found that preparations of purified bovine rod photoreceptor cyclic nucleotide phosphodiesterase (PDE) contain 1.8 ± 0.3 mol of tightly bound cGMP per mol of PDE. When subunits of the purified PDE were separated by reverse-phase HPLC, a peak of material having spectral properties characteristic of a guanine ring was seen. This material was identified as cGMP. When incubated with 1μM [3H]cGMP, only 0.1 mol of [3H]cGMP bound per mol of purified PDE. Scatchard plots of [3H]cGMP binding have indicated that two classes of binding sites are present on the rod PDE. The observation that stoichiometric amounts of cGMP are tightly bound to PDE accounts for the inability to purify the bovine rod PDE on cGMP affinity columns or to demonstrate stoichiometric high-affinity binding sites with [3H]cGMP. More significantly, the tightly bound cGMP may resolve the apparent discrepancy between the free and total cGMP concentrations of photoreceptor outer segments

  5. Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation.

    Kim, Jeong Joo; Lorenz, Robin; Arold, Stefan T; Reger, Albert S; Sankaran, Banumathi; Casteel, Darren E; Herberg, Friedrich W; Kim, Choel

    2016-05-01

    Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. PMID:27066748

  6. Qualification of the GMP compliant FDG production and distribution unit

    Recently we installed in our laboratory a GMP-compliant compact combined FDG production and dose distribution unit. This unit, constructed by HWM, Rossendorf, consists of the mini-cell, housing the FDG synthesis module from GE, standing side-by-side with the class A shielded isolator containing remotelly controlled dose distribution module. Use of the isolator technology combined with laminar flow HEPA filtered air inside the dose distribution hot-cell allows to achieve class A environment for the aseptic filing of FDG into the opened sterile vials. Synthesis of FDG and preparation of the mother batch solution is achieved inside the hot-cells providing class C clean room environement. The whole production unit is standing in the class D laboratory. The complete set of IQ-OQ-PQ tests was performed to assure that the FDG production and distribution unit is performing accordingly to GMP requirements and is providing the product of consistent quality. The majour component in the qualification tests are the aseptic procedure validations, which consisted of the procedures recommended by GMP guidelines and adapted for the specificity of the FDG production. As a minimum for the aseptic validation we considered the Mediafil Test, Bioburden Test and test productions. All the test results assure that the FDG production unit allows to produce FDG for central distribution in accordance with the requirements of European pharmacopoeia and GMP guidelines. (author)

  7. Implementation of good manufacturing practices (GMP) on human blood irradiation

    The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO4: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

  8. Good manufacturing practices (GMP utilized on human blood irradiation process

    Cláudio Boghi

    2008-01-01

    Full Text Available Irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease, a rare but devastating adverse effect of leukocytes present in blood components for immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25Gy to 50Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO4: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation.

  9. Implementation of good manufacturing practices (GMP) on human blood irradiation

    Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: cboghi@uol.com.br; cmnapoli@ipen.br; dancarde@ig.com.br; prela@ipen.br; Zarate, Herman S. [Comission Chilena de Energia Nuclear, Santiago (Chile)]. E-mail: hzarate@cchen.cl

    2007-07-01

    The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO{sub 4}: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

  10. Cyclic GMP alters Ca exchange in vascular smooth muscle

    Contraction and 42K efflux from vascular smooth muscle stimulated either by norepinephrine (NE) or by K-depolarization is dependent on an increase in cytosolic Ca concentration. The purpose of this study was to determine if cyclic GMP (cGMP) inhibited these processes and if inhibition was secondary to the action of cGMP on Ca movements. Basal cGMP content of rat aorta was 1.2 fmol/mg wet wt. Sodium nitroprusside (NP) increased cGMP ∼2-fold at 1 nM and ∼750-fold at 1 μM with no effect on cAMP levels. A 5 min pretreatment with NP (1 μM) completely prevented tension development induced by 3 μM NE. The same concentration of NP also inhibited NE-stimulated 42K and 45Ca efflux > 90 and > 80%, respectively. Removal of NP in the continued presence of NE (3 μM) caused recovery of the 42K efflux response to ∼75% of control with a half-time of ∼2.5 min. NP (1 μM) also caused a rapid relaxation of aorta contracted with 3 μM NE and a loss of the 42K efflux response with half-times of 2-3 min. In contrast, 100 μM NP produced only a 50% inhibition of contraction induced by high K (55 mM). Also, NP (1 μM) inhibited K-stimulated 42K efflux only ∼25%. These results demonstrate both a concentration- and a time-dependent relationship between increases in cGMP induced by NP and decreases in NE-stimulated contraction, 42K and 45Ca effluxes. They also indicate that the sensitivity of NE-induced contraction and 42K efflux to NP is greater than that induced by high K. These studies suggest that cGMP modulates the control sites for Ca exchange in the plasma membrane and sarcoplasmic reticulum

  11. Hydrogen peroxide is involved in cGMP modulating the lateral root development of Arabidopsis thaliana

    Li, Jisjeng; Jia, Honglei

    2013-01-01

    3′,5′-cyclic guanosine monophosphate (cGMP) and hydrogen peroxide (H2O2) function as the important signaling molecule which promote the lateral root development of Arabidopsis thaliana. In this study, interestingly, application of 8-Br-cGMP (the membrane permeable cGMP analog) promoted the endogenous H2O2 production. In addition, the decrease of endogenous H2O2 also inhibited the effect of cGMP on the lateral root development. Thus, H2O2 maybe act as a downstream signaling of cGMP molecule wh...

  12. 13th international symposium on autoradiography (13th ISA '83)

    At the conference, 39 papers were heard all of which are included in INIS. Topics covered include: trends in development of solid state track detectors, theory and methods of quantitative autoradiography, equipment for autoradiographs processing and track counting, uses of autoradiography in research of semiconductors, in metallography and in biology

  13. Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes

    Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2+-channel current (ICa) through the opposite actions for two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent protein kinase, inhibition of ICa by cyclic GMP in frog heart is largely mediated by activation of cyclic AMP phosphodiesterase. The present patch-clamp study reveals that, in rat ventricular cells, cyclic GMP can also regulate ICa via activation of endogenous cyclic GMP-dependent protein kinase (cGMP-PK). Indeed, the effect of cyclic GMP on ICa was mimicked by intracellular perfusion with the proteolytic active fragment of purified cGMP-PK. Moreover, cGMP-PK immunoreactivity was detected in pure rat ventricular myocytes by using a specific polyclonal antibody. These results demonstrate a dual mechanism for the inhibitory action of cyclic GMP in heart, as well as a physiological role for cGMP-PK in the control of mammalian heart function

  14. c-di-GMP and its Effects on Biofilm Formation and Dispersion: a Pseudomonas Aeruginosa Review.

    Ha, Dae-Gon; O'Toole, George A

    2015-04-01

    Since its initial discovery as an allosteric factor regulating cellulose biosynthesis in Gluconacetobacter xylinus, the list of functional outputs regulated by c-di-GMP has grown. We have focused this article on one of these c-di-GMP-regulated processes, namely, biofilm formation in the organism Pseudomonas aeruginosa. The majority of diguanylate cyclases and phosphodiesterases encoded in the P. aeruginosa genome still remain uncharacterized; thus, there is still a great deal to be learned about the link between c-di-GMP and biofilm formation in this microbe. In particular, while a number of c-di-GMP metabolizing enzymes have been identified that participate in reversible and irreversible attachment and biofilm maturation, there is a still a significant knowledge gap regarding the c-di-GMP output systems in this organism. Even for the well-characterized Pel system, where c-di-GMP-mediated transcriptional regulation is now well documented, how binding of c-di-GMP by PelD stimulates Pel production is not understood in any detail. Similarly, c-di-GMP-mediated control of swimming, swarming and twitching also remains to be elucidated. Thus, despite terrific advances in our understanding of P. aeruginosa biofilm formation and the role of c-di-GMP in this process since the last version of this book (indeed there was no chapter on c-di-GMP!) there is still much to learn. PMID:26104694

  15. Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death.

    Montoliu, C; Llansola, M; Monfort, P; Corbalan, R; Fernandez-Marticorena, I; Hernandez-Viadel, M L; Felipo, V

    2001-04-01

    Glutamate is the main excitatory neurotransmitter in mammals. However, excessive activation of glutamate receptors is neurotoxic, leading to neuronal degeneration and death. In many systems, including primary cultures of cerebellar neurons, glutamate neurotoxicity is mainly mediated by excessive activation of NMDA receptors, leading to increased intracellular calcium which binds to calmodulin and activates neuronal nitric oxide synthase (NOS), increasing nitric oxide (NO) which in turn activates guanylate cyclase and increases cGMP. Inhibition of NOS prevents glutamate neurotoxicity, indicating that NO mediates glutamate-induced neuronal death in this system. NO generating agents such as SNAP also induce neuronal death. Compounds that can act as "scavengers" of NO such as Croman 6 (CR-6) prevent glutamate neurotoxicity. The role of cGMP in the mediation of glutamate neurotoxicity remains controversial. Some reports indicate that cGMP mediates glutamate neurotoxicity while others indicate that cGMP is neuroprotective. We have studied the role of cGMP in the mediation of glutamate and NO neurotoxicity in cerebellar neurons. Inhibition of soluble guanylate cyclase prevents glutamate and NO neurotoxicity. There is a good correlation between inhibition of cGMP formation and neuroprotection. Moreover 8-Br-cGMP, a cell permeable analog of cGMP, induced neuronal death. These results indicate that increased intracellular cGMP is involved in the mechanism of neurotoxicity. Inhibitors of phosphodiesterase increased extracellular but not intracellular cGMP and prevented glutamate neurotoxicity. Addition of cGMP to the medium also prevented glutamate neurotoxicity. These results are compatible with a neurotoxic effect of increased intracellular cGMP and a neuroprotective effect of increased extracellular cGMP. PMID:14715472

  16. Possible impacts of early-11th-, middle-12th-, and late-13th-century droughts on western Native Americans and the Mississippian Cahokians

    Benson, Larry V.; Berry, Michael S.; Jolie, Edward A.; Spangler, Jerry D.; Stahle, David W.; Hattori, Eugene M.

    2007-02-01

    One or more of three intense and persistent droughts impacted some Native American cultures in the early-11th, middle-12th and late-13th centuries, including the Anasazi, Fremont, Lovelock, and Mississippian (Cahokian) prehistorical cultures. Tree-ring-based reconstructions of precipitation and temperature indicate that warm drought periods occurred between AD 990 and 1060, AD 1135 and 1170, and AD 1276 and 1297. These droughts occurred during minima in the Pacific Decadal Oscillation and may have been associated with positive values of the Atlantic Multidecadal Oscillation. Each of the Native American cultures was supported, to a greater or lesser degree, by precipitation-dependent resources. Both the Four Corners region and Cahokia were sites of intense growth between about AD 1050 and 1130, and by AD 1150, cultures in both regions were undergoing stress. By AD 1300 the Anasazi and Fremont cultures had collapsed and their residual populations had either left their homelands or withered. In the case of Fremont populations, the AD 990-1060 drought may have had the greatest impact. This drought also may have affected the Anasazi, for it was at the end of this drought that some people from Chaco migrated to the San Juan River valley and founded the Salmon Ruin great house. Detailed data do not exist on the number of Lovelock habitation sites or populations over time; however, Lovelock populations appear to have retreated from the western Great Basin to California by AD 1300 or shortly thereafter.

  17. Results of 13th regular inspection of No.1 plant in Fukushima No.1 Nuclear Power Station, Tokyo Electric Power Co., Inc

    The 13th regular inspection of No.1 plant in Fukushima No.1 Nuclear Power Station was carried out from November 20, 1987 to April 27, 1988. The parallel operation was resumed on April 8, 1988, 141 days after the parallel-off. The facilities being the object of inspection were the reactor proper, reactor cooling system, measuring and control system, fuel facilities, radiation control facilities, waste facilities, reactor containment installation, and emergency power generation system. On these facilities being the object of inspection, the appearance, disassembling, leak, function, performance and other inspections were carried out, as the result, abnormality was not found at all. The works related to this regular inspection were accomplished within the range of allowable radiation dose based on the relevant laws. The main reconstruction works carried out during the period of this regular inspection were the charging of 52 new 8 x 8 zirconium liner fuel assemblies for improving the reliability and capacity factor, the new installation of a hollow thread film filter before the condensate desalting facility for reducing its load, the repair of a core spray piping, the installation of process radiation monitors, the replacement of a movable spatial dose rate measuring instrument, the repair of the penetration through the reactor containment vessel, the replacement of a condensate system piping and the repair of the exhaust gas condenser. (Kako, I.)

  18. A glimpse into the early origins of medieval anatomy through the oldest conserved human dissection (Western Europe, 13th c. A.D.)

    Huynh-Charlier, Isabelle; Poupon, Joël; Lancelot, Eloïse; Campos, Paula F.; Favier, Dominique; Jeannel, Gaël-François; Bonati, Maurizio Rippa; de la Grandmaison, Geoffroy Lorin; Hervé, Christian

    2013-01-01

    Introduction Medieval autopsy practice is very poorly known in Western Europe, due to a lack of both descriptive medico-surgical texts and conserved dissected human remains. This period is currently considered the dark ages according to a common belief of systematic opposition of Christian religious authorities to the opening of human cadavers. Material and methods The identification in a private collection of an autopsied human individual dated from the 13th century A.D. is an opportunity for better knowledge of such practice in this chrono-cultural context, i.e. the early origins of occidental dissections. A complete forensic anthropological procedure was carried out, completed by radiological and elemental analyses. Results The complete procedure of this body opening and internal organs exploration is explained, and compared with historical data about forensic and anatomical autopsies from this period. During the analysis, a red substance filling all arterial cavities, made of mercury sulfide (cinnabar) mixed with vegetal oil (oleic and palmitic acids) was identified; it was presumably used to highlight vascularization by coloring in red such vessels, and help in the preservation of the body. Conclusions Of particular interest for the description of early medical and anatomical knowledge, this “human preparation” is the oldest known yet, and is particularly important for the fields of history of medicine, surgery and anatomical practice. PMID:24904674

  19. Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology

    Klotz Lars-Oliver

    2010-02-01

    Full Text Available Abstract The 13th meeting of the Signal Transduction Society was held in Weimar, from October 28 to 30, 2009. Special focus of the 2009 conference was "Aging and Senescence", which was co-organized by the SFB 728 "Environmentally-Induced Aging Processes" of the University of Düsseldorf and the study group 'Signal Transduction' of the German Society for Cell Biology (DGZ. In addition, several other areas of signal transduction research were covered and supported by different consortia associated with the Signal Transduction Society including the long-term associated study groups of the German Society for Immunology and the Society for Biochemistry and Molecular Biology, and for instance the SFB/Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" located in Würzburg, Mainz and Berlin. The different research areas that were introduced by outstanding keynote speakers attracted more than 250 scientists, showing the timeliness and relevance of the interdisciplinary concept and exchange of knowledge during the three days of the scientific program. This report gives an overview of the presentations of the conference.

  20. Seeding the FEL of the SCSS Phase 1 Facility with the 13th Laser Harmonic of a Ti Sa Laser (61.5 nm) Produced in Xe Gas

    Lambert, G; Boutu, W; Breger, P; Couprie, M E; Garzella, D; Merdji, H; Monchicourt, P; Salieres, P

    2005-01-01

    In order to reach very short wavelengths in FEL, and to have a more compact, fully coherent and tunable source, a particular seeding configuration is foreseen to be tested as a demonstration experiment in 2006 into the SCSS phase 1 facility (Spring-8 Compact Sase Source, Japan). The external source is the 13th harmonic (61.5 nm) of a Ti: Sa laser (25 mJ, 10 Hz, 100 fs) generated in 10 Hz pulsed Xe gas cell. The harmonic generation process provides us with a intense (1 μJ) and ultra-short (50 fs) VUV beam. The design of the experiment implantation is discussed, taken into account the performances of the generation process, the focusing of the selected harmonic into the modulator, and the resistance of the optical components. Besides one should consider the vacuum needs, the geometrical problems and the mechanics for the under UHV mirrors translation. One first chamber is dedicated to the harmonic generation. A second one is used for spectral selection and adaptation of the harmonic in the modulator. F...

  1. Design of GMP compliance radiopharmaceutical production facility in MINT

    In 1985, MINT built the only radiopharmaceutical production facility in Malaysia. The facility was designed based on IAEA (International Atomic Energy Agency) standard guidelines which provide radiation safety to the staff and the surrounding environment from radioactive contamination. Since 1999, BPFK (Biro Pengawalan Farmaseutikal Kebangsaan) has used the guidelines from Pharmaceutical Inspection Convention Scheme (PICS) to meet the requirements of the Good Manufacturing Practice (GMP) for Pharmaceutical Products. In the guidelines, the pharmaceutical production facility shall be designed based on clean room environment. In order to design a radiopharmaceutical production facility, it is important to combine the concept of radiation safety and clean room to ensure that both requirements from GMP and IAEA are met. The design requirement is necessary to set up a complete radiopharmaceutical production facility, which is safe, has high production quality and complies with the Malaysian and International standards. (Author)

  2. cGMP in ozone and NO dependent responses

    Ederli, Luisa; Meier, Stuart; Borgogni, Andrea; Reale, Lara; Ferranti, Francesco; Gehring, Chris

    2008-01-01

    We have recently reported that ozone (O3) can inhibit mitochondrial respiration and induce activation of the alternative oxidase (AOX) pathway and in particular AOX1a in tobacco. While O3 causes mitochondrial H2O2, early leaf nitric oxide (NO) as well as transient ethylene (ET) accumulation, the levels of jasmonic acid and 12-oxo-phytodienoic acid remained unchanged. It was shown that both, NO and ET dependent pathways can induce AOX1a transcription by O3. AOX plays a role in reducing reactive oxygen species (ROS) which in turn are linked to biotic and abiotic plant stresses, much like the second messengers guanosine 3′, 5′-cyclic monophosphate (cGMP). The goal is to unravel specific cGMP signatures and induction pathways downstream from O3 and NO, including transcription of AOX1a. Here we propose that some late (>3 h) responses to NO, e.g., the accumulation of phenylalanine lyase (PAL) transcripts, are critically cGMP dependent, while the early (<2 h) responses, including AOX1a induction are not. PMID:19704720

  3. Report of the Two-Day National Seminar on New Directions in Higher Education, Organized by the Kerala State Higher Education Council on 12th and 13th July 2010

    Praveen, C.

    2010-01-01

    This is a report of the Two-Day National Seminar on New Directions in Higher Education, organized by the Kerala State Higher Education Council on 12th and 13th July 2010. The objective of the seminar was to deliberate upon the reforms being undertaken by the Government of India in Higher Education. Reputed scholars from within and outside the…

  4. A study on relations between the levels of GMP-140 and microangiopathy in NIDDM

    The relations between the level of GMP-140 and microangiopathy in NIDDM for earlier diagnosis or better treatment are investigated, the level of GMP-140 in both platelet and plasma was measured. The level of GMP-140 in both platelet and plasma in 104 cases with NIDDM (55 with and 49 without microagiopathy) and 38 controls were assayed by RIA and also simultaneously with direct platelet count. The level of GMP-140 in both platelet and plasma in NIDDM was remarkably higher than that in controls (P1 = 0.69, r2 = 0.75). No differences existed in platelet count between NIDDM and controls. The level of GMP-140 and ophthalmoscopic study had no change after decreasing the concentration of blood glucose (<7.8 mmol/L) and administrating aspirin for 6 months. Microangiopathy in NIDDM had close relation with platelet function and the level of GMP-140

  5. Effect of ionizing radiation of tissue cyclic AMP and GMP in experimental rats

    Adult male Sprague Dawley rats were exposed to whole-body gamma radiation of 4 Gy and 10 Gy and cyclic AMP and GMP of several tissues were studied 4 hours, 24 hours and 72 hours after irradiation. Animals exposed to 4 Gy exhibited initial increase and subsequent decrease of plasma cyclic AMP, while opposite effects were noted in plasma cyclic GMP. Both groups of irradiated rats showed significant decrease of spleen cyclic AMP with variable responses in cyclic GMP. Initial increase with subsequent decrease of liver cyclic AMP was observed in irradiated animals with unaltered cyclic GMP values. It was interesting to note variable responses of myocardial cyclic AMP in both groups of experimental rats with a significant increase in heart cyclic GMP in rats exposed to 10 Gy only. In contrast, myocardial cyclic GMP was significantly decreased in rats exposed to 4 Gy groups. (orig.)

  6. Early Old Bulgarian Layer in the Office Menaion of Rostov Provenance of the 13th c. (RNL, F.p.I 37

    Roman N. Krivko

    2012-08-01

    Full Text Available The article is dedicated to the linguistic and textual peculiarities of the Festal Menaion F. p. I 37 preserved in Russian National Library (S.-Petersburg and dated to the beginning of the 13th c. Numerous linguistic features of the manuscript testify to Old West Bulgarian (Old Macedonian literary usage of the end of the 9th — beginning of the 10th c., on the basis of which the earliest Slavonic hymnographical translations were performed. Despite of such an archaic linguistic and textual layers observed in the manuscript, its calendar, structure and content were influenced by the monastic rite based on the Typicon of Patriarch Alexius the Studite which had been translated and introduced in Kievan Rus' at the second half of the 11th c. The linguistic features of the text version as attested by F. p. I 37 have been compared to the manuscripts testifying to the Alexius the Studite text version. It has been affirmed that adaptation of the Old Bulgarian hymnographic heritage in Kievan Rus' followed the unstable trend to neglect the most remarkable South (and South West Slavonic lingustic features and aimed at establishing “neutral” over dialectal Church Slavonic literary usage. The significant part of the article contains the edition of the earliest Slavonic, i.e., Old Bulgarian, translation of the Greek kanon Τάφῳ παρθενοδόχῳ dedicated to the Dormition of the Theotokos. The earliest Slavonic translation of this kanon has been preserved in the unique available manuscript, that is F. p. I 37. The publication of the Slavonic translation is supplied with the first critical edition of the Greek source performed on the basis of twelve manuscripts, the linguistic commentary of the Slavonic text, and remarks concerning some metric peculiarities of the original Greek version.

  7. RIA of platelet GMP-140 in patients with coronary heart disease

    With monoclonal antibody SZ-51, the activated levels of the platelet granule membrane protein (GMP-140) of 94 cases with coronary heart disease (CHD) are assayed by RIA. The results show that the levels of GMP-140 with CHD are much higher than those of the controls (P<0.001), and the levels of GMP-140 with AMI 12 hours after the treatment with urokinase for thrombolysis are considerably lower than the levels one hour before the treatment. Therefore, the assay of GMP-140 with CHD is of great clinical significance in diagnosing and differentiating CHD, especially, in analysing pathogen, monitoring curative effect and predicting prognosis for AMI

  8. Study of GMP-140 RIA in the diagnosis and treatment of cerebrovascular diseases

    To investigate the relation between GMP-140 with the progress and mechanism of cerebrovascular diseases, the level of GMP-140 in both platelet and plasma in 76 cases of cerebrovascular disease and 35 normal controls were determined by radioimmunoassay (RIA). Results showed that the level of GMP-140 in both platelet and plasma of cerebrovascular diseases were remarkably higher than that in normal controls (P0.05). It was concluded that the progress, development, and prognosis of cerebrovascular diseases is strongly related to the platelet function and the level of GMP-140

  9. A study in platelet GMP-140 for coronary heart disease by RIA

    With monoclonal anti-body SZ-51, activated levels of platelet granule membrane protein (GMP-140) in coronary heart disease (CHD) were assayed by RIA. The results showed that the levels of GMP-140 with CHD were higher than that of controls (P>0.001). The levels of GMP-140 with AMI treated with urokinase for thrombolysis in 12 hours were considerably lower than that one hour before treatment. Therefore, the measurement of GMP-140 with CHD is of great clinical value in diagnosing and differentiating AMI, especially, in analysing pathogen, monitoring curative effect and predicting prognosis for AMI

  10. Intracellular photoactivation of caged cGMP induces myosin II and actin responses in motile cells.

    Pfannes, Eva K B; Anielski, Alexander; Gerhardt, Matthias; Beta, Carsten

    2013-12-01

    Cyclic GMP (cGMP) is a ubiquitous second messenger in eukaryotic cells. It is assumed to regulate the association of myosin II with the cytoskeleton of motile cells. When cells of the social amoeba Dictyostelium discoideum are exposed to chemoattractants or to increased osmotic stress, intracellular cGMP levels rise, preceding the accumulation of myosin II in the cell cortex. To directly investigate the impact of intracellular cGMP on cytoskeletal dynamics in a living cell, we released cGMP inside the cell by laser-induced photo-cleavage of a caged precursor. With this approach, we could directly show in a live cell experiment that an increase in intracellular cGMP indeed induces myosin II to accumulate in the cortex. Unexpectedly, we observed for the first time that also the amount of filamentous actin in the cell cortex increases upon a rise in the cGMP concentration, independently of cAMP receptor activation and signaling. We discuss our results in the light of recent work on the cGMP signaling pathway and suggest possible links between cGMP signaling and the actin system. PMID:24136144

  11. Annual energy review 1994

    NONE

    1995-07-01

    This 13th edition presents the Energy Information Administration`s historical energy statistics. For most series, statistics are given for every year from 1949 through 1994; thus, this report is well-suited to long-term trend analyses. It covers all major energy activities, including consumption, production, trade, stocks, and prices for all major energy commodities, including fossil fuels and electricity. Statistics on renewable energy sources are also included: this year, for the first time, usage of renewables by other consumers as well as by electric utilities is included. Also new is a two-part, comprehensive presentation of data on petroleum products supplied by sector for 1949 through 1994. Data from electric utilities and nonutilities are integrated as ``electric power industry`` data; nonutility power gross generation are presented for the first time. One section presents international statistics (for more detail see EIA`s International Energy Annual).

  12. Atrial natriuretic peptide and oxytocin induce natriuresis by release of cGMP

    Soares, T. J.; Coimbra, T. M.; Martins, A. R.; Pereira, A. G. F.; Carnio, E. C.; Branco, L. G. S.; Albuquerque-Araujo, W. I. C.; de Nucci, G.; Favaretto, A. L. V.; Gutkowska, J.; McCann, S. M.; Antunes-Rodrigues, J.

    1999-01-01

    Our hypothesis is that oxytocin (OT) causes natriuresis by activation of renal NO synthase that releases NO followed by cGMP that mediates the natriuresis. To test this hypothesis, an inhibitor of NO synthase, l-nitroarginine methyl ester (NAME), was injected into male rats. Blockade of NO release by NAME had no effect on natriuresis induced by atrial natriuretic peptide (ANP). This natriuresis presumably is caused by cGMP because ANP also activates guanylyl cyclase, which synthesizes cGMP from GTP. The 18-fold increase in sodium (Na+) excretion induced by OT (1 μg) was accompanied by an increase in urinary cGMP and preceded by 20 min a 20-fold increase in NO3− excretion. NAME almost completely inhibited OT-induced natriuresis and increased NO3− excretion; however, when the dose of OT was increased 10-fold, a dose that markedly increases plasma ANP concentrations, NAME only partly inhibited the natriuresis. We conclude that the natriuretic action of OT is caused by a dual action: generation of NO leading to increased cGMP and at higher doses release of ANP that also releases cGMP. OT-induced natriuresis is caused mainly by decreased tubular Na+ reabsorption mediated by cGMP. In contrast to ANP that releases cGMP in the renal vessels and the tubules, OT acts on its receptors on NOergic cells demonstrated in the macula densa and proximal tubules to release cGMP that closes Na+ channels. Both ANP- and OT-induced kaliuresis also appear to be mediated by cGMP. We conclude that cGMP mediates natriuresis and kaliuresis induced by both ANP and OT. PMID:9874809

  13. Cyclic GMP protects human macrophages against peroxynitrite-induced apoptosis

    Rossi Adriano G

    2009-05-01

    Full Text Available Abstract Background Nitric oxide (NO can be both pro- and anti-apoptotic in various cell types, including macrophages. This apparent paradox may result from the actions of NO-related species generated in the microenvironment of the cell, for example the formation of peroxynitrite (ONOO-. In this study we have examined the ability of NO and ONOO- to evoke apoptosis in human monocyte-derived macrophages (MDMϕ, and investigated whether preconditioning by cyclic guanosine monophosphate (cGMP is able to limit apoptosis in this cell type. Methods Characterisation of the NO-related species generated by (Z-1- [2-(2-aminoethyl-N-(2-ammonioethylamino]diazen-1-ium-1,2-diolate (DETA/NO and 1,2,3,4-oxatriazolium, 5-amino-3-(3,4-dichlorophenyl-, chloride (GEA-3162 was performed by electrochemistry using an isolated NO electrode and electron paramagnetic resonance (EPR spectrometry. Mononuclear cells were isolated from peripheral blood of healthy volunteers and cultured to allow differentiation into MDMϕ. Resultant MDMϕ were treated for 24 h with DETA/NO (100 – 1000 μM or GEA-3162 (10 – 300 μM in the presence or absence of BAY 41–2272 (1 μM, isobutylmethylxanthine (IBMX; 1 μM, 1H- [1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ; 20 μM or 8-bromo-cGMP (1 mM. Apoptosis in MDMϕ was assessed by flow cytometric analysis of annexin V binding in combination with propidium iodide staining. Results Electrochemistry and EPR revealed that DETA/NO liberated free NO radical, whilst GEA-3162 concomitantly released NO and O2-, and is therefore a ONOO- generator. NO (DETA/NO had no effect on cell viability, but ONOO- (GEA-3162 caused a concentration-dependent induction of apoptosis in MDMϕ. Preconditioning of MDMϕ with NO in combination with the phosphodiesterase inhibitor, 3-Isobutyl-1-methylxanthine (IBMX, or the NO-independent stimulator of soluble guanylate cyclase, BAY 41–2272, significantly attenuated ONOO--induced apoptosis in a cGMP-dependent manner

  14. Methods and materials relating to IMPDH and GMP production

    Collart, Frank R.; Huberman, Eliezer

    1997-01-01

    Disclosed are purified and isolated DNA sequences encoding eukaryotic proteins possessing biological properties of inosine 5'-monophosphate dehydrogenase ("IMPDH"). Illustratively, mammalian (e.g., human) IMPDH-encoding DNA sequences are useful in transformation or transfection of host cells for the large scale recombinant production of the enzymatically active expression products and/or products (e.g., GMP) resulting from IMPDH catalyzed synthesis in cells. Vectors including IMPDH-encoding DNA sequences are useful in gene amplification procedures. Recombinant proteins and synthetic peptides provided by the invention are useful as immunological reagents and in the preparation of antibodies (including polyclonal and monoclonal antibodies) for quantitative detection of IMPDH.

  15. Captive solvent [11C]acetate synthesis in GMP conditions

    Reliable procedure for the production of 1-[11C]acetate in GMP conditions was developed based on a combination of the captive-solvent Grignard reaction conducted in the sterile catheter followed by the convenient solid-phase extraction purification on a series of ion-exchange cartridges. The described procedure proved to be reliable in more than 30 patient productions. The process provides stable radiochemical yields (65% EOB) of sodium acetate (1-[11C]) of the Ph.Eur. quality (radiochemical purity better than 95%) in a short time (5 min)

  16. Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth.

    Dhayade, Sandeep; Kaesler, Susanne; Sinnberg, Tobias; Dobrowinski, Hyazinth; Peters, Stefanie; Naumann, Ulrike; Liu, He; Hunger, Robert E; Thunemann, Martin; Biedermann, Tilo; Schittek, Birgit; Simon, Hans-Uwe; Feil, Susanne; Feil, Robert

    2016-03-22

    Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked to an increased risk of melanoma. Here, we have examined the potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination of biochemical assays and real-time monitoring of melanoma cells, we report a cGMP-dependent growth-promoting pathway in murine and human melanoma cells. We document that C-type natriuretic peptide (CNP), a ligand of the membrane-bound guanylate cyclase B, enhances the activity of cGMP-dependent protein kinase I (cGKI) in melanoma cells by increasing the intracellular levels of cGMP. Activation of this cGMP pathway promotes melanoma cell growth and migration in a p44/42 MAPK-dependent manner. Sildenafil treatment further increases intracellular cGMP concentrations, potentiating activation of this pathway. Collectively, our data identify this cGMP-cGKI pathway as the link between sildenafil usage and increased melanoma risk. PMID:26971999

  17. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

    Robert W Moon

    2009-09-01

    Full Text Available The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta, unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta, showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.

  18. Detection of plasma granule membrane protein (GMP-140) using radiolabelled monoclonal antibodies in thrombotic diseases

    Radioimmunoassay with two monoclonal antibodies to granule membrane protein (GMP-140) is used to determine whether plasma GMP-140 including its soluble and microparticle forms can be detected in patients with acute myocardial infarction (AMI) or during cardio-pulmonary bypass (CPB) and in platelet concentrates during storage. Monoclonal antibody (McAb) SZ-51 was used as a solid phase and 125I-labelled McAb S12 was used as a fluid phase. The assay showed sufficient sensitivity to detect as few as 1 ng/mL of purified GMP-140. There was only 10.0 ± 4.5 ng/mL in normal plasma (n 20) with no significant different between the male and the female controls. Ten patients undergoing CPB demonstrated a transient increase in the concentration of plasma GMP-140, especially 2 h after CPB, and its plasma level was inversely correlated with the platelet counting during bypass (r -0.81, P < 0.01). Patients with AMI (n = 16) were found to have significantly increased concentration of plasma GMP-140 after AMI, reaching the peak within 3 days and changing with the progression of AMI. The concentration of plasma GMP-140 increased progressively in platelet concentrates during storage, particularly 5 days after storage. In short, these data suggest that plasma GMP-140 can be reliably detected by radioimmunoassay with two McAbs to GMP-140 and its plasma level may serve as a useful marker of thrombosis and thrombotic diseases

  19. Sildenafil Potentiates a cGMP-Dependent Pathway to Promote Melanoma Growth

    Sandeep Dhayade

    2016-03-01

    Full Text Available Sildenafil, an inhibitor of the cGMP-degrading phosphodiesterase 5 that is used to treat erectile dysfunction, has been linked to an increased risk of melanoma. Here, we have examined the potential connection between cGMP-dependent signaling cascades and melanoma growth. Using a combination of biochemical assays and real-time monitoring of melanoma cells, we report a cGMP-dependent growth-promoting pathway in murine and human melanoma cells. We document that C-type natriuretic peptide (CNP, a ligand of the membrane-bound guanylate cyclase B, enhances the activity of cGMP-dependent protein kinase I (cGKI in melanoma cells by increasing the intracellular levels of cGMP. Activation of this cGMP pathway promotes melanoma cell growth and migration in a p44/42 MAPK-dependent manner. Sildenafil treatment further increases intracellular cGMP concentrations, potentiating activation of this pathway. Collectively, our data identify this cGMP-cGKI pathway as the link between sildenafil usage and increased melanoma risk.

  20. Structural Basis of Ligand Binding by a C-di-GMP Riboswitch

    Smith, K.; Lipchock, S; Ames, T; Wang, J; Breaker, R; Strobel, S

    2009-01-01

    The second messenger signaling molecule bis-(3{prime}-5{prime})-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 {angstrom} resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structural data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling.

  1. Structural basis of ligand binding by a c-di-GMP riboswitch.

    Smith, Kathryn D; Lipchock, Sarah V; Ames, Tyler D; Wang, Jimin; Breaker, Ronald R; Strobel, Scott A

    2009-12-01

    The second messenger signaling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 A resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structural data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling. PMID:19898477

  2. The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi

    Elizabeth A. Novak

    2014-05-01

    Full Text Available In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease.

  3. The institutions forming the socioeconomic structure of Turkish private enterprises between the 13th and the 19th centuries: Akhism, the Lonca system and the Gedik system

    Mehmet Özbirecikli

    2010-12-01

    principios éticos de la vida empresarial, en esencia, son los mismos. Dentro de este contexto, nos atrevemos a sugerir que las raíces del código ético de la vida empresarial turca se retrotraen en la historia a hace más de 800 años. Además, la similitud entre el funcionamiento presente y pasado indica que el origen de la formación de los aprendices para las empresas turcas tiene, igualmente, más de 800 años de historia.This study investigates three institutions forming the socioeconomic structure of Turkish private enterprises between the 13th and 19th Centuries: Akhism (13th-16th century, the Lonca System (the Guilds (16th-18th century, and the Gedik (Monopoly System (18th-20th century. The study particularly focuses on the social and economic rules, vocational training process, and organizational structure of the said institutions in order to discuss the effects of the socioeconomic structure of Turkish enterprises on economic and social development of private enterprises. The study also struggles to link between the relevant current applications and the applications in the past such as the social rules and vocational training. From economic point of view, both the statist structure of the State and the economic rules of the institutions herein caused private enterprises to remain small, and prevented them from having a competitive environment and having capital accumulation. As a result, enterprises could not benefit from new production techniques and the Turkish enterprise mentality fell behind modern developments. On the other hand, although these three systems were completely abolished in the early 20th Century, it is seen that especially traces of the Akhism and Lonca systems have still been surviving. Both the most of rules of Akhism and some of the duties of the board of directors of Lonca such as keeping moral standards of production and trade remind us of professional code of ethics of today’s modern business life. In other saying, there was code of

  4. Purification and characterization of cGMP binding protein-phosphodiesterase from rat lung

    The cGMP binding protein-phosphodiesterase (cG-BPP) with a phosphodiesterase specific activity of 7 μM/min/mg has been purified from rat lung by sequential chromatography on DEAE-cellulose, Blue-Sepharose, zinc chelate affinity adsorbent and HPLC-DEAE. Migration of the major band on SDS-PAGE corresponds to a MW of ∼93,000. Both cGMP phosphodiesterase activity and cGMP binding from the HPLC-DEAE profile correlate with this band. Since the authors previous work has determined the native MW to be ∼177,000, this suggests a dimeric structure comprised of two 93,000 MW subunits for the rat lung cG-BPP. At low cGMP concentrations, cGMP binding is stimulated ∼20-fold by histone and ∼5-fold by 3-isobutyl-1-methylxanthine(IBMX). The purified protein has one component of cGMP dissociation with a rate constant of 0.045/min. Photolysis of the purified protein in the presence of 32P-cGMP labels the 93,000 MW band and this labeling is increased by IBMX, indicating that the 93,000 MW band is a subunit of the cGMP-BPP. This implies that the enzyme preparation is nearly homogeneous, a conclusion also supported by a minimum [3H]-cGMP binding stoichiometry of 0.5 mol per 93,000 subunit. An additional protein band with a MW of ∼90,000 also occurs in these preparations which exhibits behavior similar to the 93,000 MW protein. N2-Hexyl-cGMP inhibits phosphodiesterase activity by competing with cGMP for hydrolysis at the catalytic site but not at the binding site. N2-Hexyl cGMP actually increases cGMP binding. This provides the first evidence that cGMP binding is increased by compounds hydrolyzed at the catalytic site. This interaction between the binding and phosphodiesterase sites could be important in the regulation of the functions of these sites in vivo

  5. Fast repair activities of quercetin and rutin toward dGMP hydroxyl radical adducts

    The repair activities and mechanisms of both quercetin and rutin towards the oxidizing deoxyguanosine monophosphate (d GMP) hydroxyl radical adduct were investigated with pulse radiolytic technique. On pulse irradiation of nitrous oxide saturated 2 mm d GMP aqueous solution containing 0.1 mm quercetin, the transient absorption spectrum of the d GMP hydroxyl radical adduct decays with the formation of phenoxyl radical of quercetin within tens of microseconds. It indicates that there is a repair reaction between d GMP hydroxyl radical adduct and quercetin. The repair activity of rutin towards hydroxyl radical adducts of d GMP was also observed. The rate constants of the repair reactions were calculated to be 3.05x108 and 1.31x108 M-1 s-1for quercetin and rutin, respectively. This result together with our previous studies demonstrated that non-enzymatic, fast repair is a universal repair mechanism of phenolic antioxidants.

  6. cGMP in Mouse Rods: the spatiotemporal dynamics underlying single photon responses

    Owen P. Gross

    2015-03-01

    Full Text Available Vertebrate vision begins when retinal photoreceptors transduce photons into membrane hyperpolarization, which reduces glutamate release onto second-order neurons. In rod photoreceptors, transduction of single photons is achieved by a well-understood G-protein cascade that modulates cGMP levels, and in turn, cGMP-sensitive inward current. The spatial extent and depth of the decline in cGMP during the single photon response have been major issues in phototransduction research since the discovery that single photons elicit substantial and reproducible changes in membrane current. The spatial profile of cGMP decline during the single photon response affects signal gain, and thus may contribute to reduction of trial-to-trial fluctuations in the single photon response. Here we summarize the general principles of rod phototransduction, emphasizing recent advances in resolving the spatiotemporal dynamics of cGMP during the single photon response.

  7. Report on the 13th symposium on invertebrate neurobiology held 26-30 August 2015 at the Balaton Limnological Institute, MTA Centre for ecological research of the Hungarian Academy of Sciences, Tihany, Hungary.

    Crisford, Anna; Holden-Dye, Lindy; Walker, Robert J

    2016-06-01

    This report summarizes the lectures and posters presented at the International Society for Invertebrate Neurobiology's 13th symposium held 26-30 August 2015, at the Balaton Limnological Institute, MTA Centre for Ecological Research, Tihany, Hungary. The symposium provided an opportunity for scientists working on a range of topics in invertebrate neurobiology to meet and present their research and discuss ways to advance the discipline. PMID:27149972

  8. The Threat of Terrorism: Putting Human Rights to the Test : Assessing the Counterterrorist Policies of France in the Aftermath of the 13th of November 2015 Terrorist Attacks 

    Poidevin, Fiore

    2016-01-01

    The terrorist attacks that occurred in Paris on the 13th of November 2015, mark a shift for counterterrorism in France. Indeed, the magnitude of the terrorist attacks persuaded the French government to call for stricter counterterrorist policies. However, the effects of these measures on human rights have been interrogated widely. Therefore, in this thesis, I wish to address the conflict between state security and individual human rights. First, I will assess if the current situation of Franc...

  9. Proceedings of the 13th International Conference on Hyperfine Interactions and 17th International Symposium on Nuclear Quadrupole Interactions (HFI/NQI 2004) Bonn, Germany, 22–27 August 2004

    Maier, K; HFI/NQI 2004

    2005-01-01

    Proceedings of the 13th International Conference on Hyperfine Interactions and 17th International Symposium on Nuclear Quadrupole Interactions, HFI/NQI 2004, held in Bonn, Germany, 22-27 August, 2004 Researchers and graduate students interested in the Mössbauer Effect and its applications will find this volume indispensable. The volume presents the most recent developments in the methodology of Mössbauer spectroscopy. Reprinted from Hyperfine Interactions (HYPE) Volume 158/159.

  10. 75 FR 17761 - Termination of an Environmental Impact Statement (EIS) for the General Management Plan (GMP) for...

    2010-04-07

    ... preparation of an EIS for the GMP for the Park, South Carolina. A Notice of Intent to prepare an EIS for the Park GMP was published in the Federal Register on October 10, 2006 (71 FR 63350), and followed by a... Plan (GMP) for Kings Mountain National Military Park (Park), South Carolina AGENCY: National...

  11. 75 FR 17756 - Availability of the Final General Management Plan and Environmental Impact Statement (GMP/EIS...

    2010-04-07

    ... (GMP/EIS) for Chattahoochee River National Recreation Area (CRNRA), GA AGENCY: National Park Service... Environmental Policy Act of 1969 the National Park Service (NPS) announces the availability of a Final GMP/EIS... CRNRA, the Final GMP/EIS describes Alternative F at the NPS preferred alternative. The...

  12. 75 FR 19422 - Availability of a Final Environmental Impact Statement for the General Management Plan (FEIS/GMP...

    2010-04-14

    ... Plan (FEIS/GMP), Tuskegee Airmen National Historic Site AGENCY: National Park Service. ACTION: Notice of availability of a Final Environmental Impact Statement for the General Management Plan (FEIS/GMP... Decision- making) the NPS announces the availability of a FEIS/GMP for the Tuskegee Airmen...

  13. Responses to elevated c-di-GMP levels in mutualistic and pathogenic plant-interacting bacteria.

    Daniel Pérez-Mendoza

    Full Text Available Despite a recent burst of research, knowledge on c-di-GMP signaling pathways remains largely fragmentary and molecular mechanisms of regulation and even c-di-GMP targets are yet unknown for most bacteria. Besides genomics or bioinformatics, accompanying alternative approaches are necessary to reveal c-di-GMP regulation in bacteria with complex lifestyles. We have approached this study by artificially altering the c-di-GMP economy of diverse pathogenic and mutualistic plant-interacting bacteria and examining the effects on the interaction with their respective host plants. Phytopathogenic Pseudomonas and symbiotic Rhizobium strains with enhanced levels of intracellular c-di-GMP displayed common free-living responses: reduction of motility, increased production of extracellular polysaccharides and enhanced biofilm formation. Regarding the interaction with the host plants, P. savastanoi pv. savastanoi cells containing high c-di-GMP levels formed larger knots on olive plants which, however, displayed reduced necrosis. In contrast, development of disease symptoms in P. syringae-tomato or P. syringae-bean interactions did not seem significantly affected by high c-di-GMP. On the other hand, increasing c-di-GMP levels in symbiotic R. etli and R. leguminosarum strains favoured the early stages of the interaction since enhanced adhesion to plant roots, but decreased symbiotic efficiency as plant growth and nitrogen contents were reduced. Our results remark the importance of c-di-GMP economy for plant-interacting bacteria and show the usefulness of our approach to reveal particular stages during plant-bacteria associations which are sensitive to changes in c-di-GMP levels.

  14. Cyclic Di-GMP modulates the disease progression of Erwinia amylovora.

    Edmunds, Adam C; Castiblanco, Luisa F; Sundin, George W; Waters, Christopher M

    2013-05-01

    The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis. PMID:23475975

  15. MRP4 Modulation of the Guanylate Cyclase-C/cGMP Pathway: Effects on Linaclotide-Induced Electrolyte Secretion and cGMP Efflux.

    Tchernychev, Boris; Ge, Pei; Kessler, Marco M; Solinga, Robert M; Wachtel, Derek; Tobin, Jenny V; Thomas, Sara R; Lunte, Craig E; Fretzen, Angelika; Hannig, Gerhard; Bryant, Alexander P; Kurtz, Caroline B; Currie, Mark G; Silos-Santiago, Inmaculada

    2015-10-01

    MRP4 mediates the efflux of cGMP and cAMP and acts as an important regulator of these secondary messengers, thereby affecting signaling events mediated by cGMP and cAMP. Immunofluorescence staining showed high MRP4 expression localized predominantly in the apical membrane of rat colonic epithelium. In vitro studies were performed using a rat colonic mucosal layer mounted in an Ussing chamber. Linaclotide activation of the guanylate cyclase-C (GC-C)/cGMP pathway induced a concentration-dependent increase in transepithelial ion current [short-circuit current (Isc)] across rat colonic mucosa (EC50: 9.2 nM). Pretreatment of colonic mucosa with the specific MRP4 inhibitor MK571 potentiated linaclotide-induced electrolyte secretion and augmented linaclotide-stimulated intracellular cGMP accumulation. Notably, pretreatment with the phosphodiesterase 5 inhibitor sildenafil increased basal Isc, but had no amplifying effect on linaclotide-induced Isc. MRP4 inhibition selectively affected the activation phase, but not the deactivation phase, of linaclotide. In contrast, incubation with a GC-C/Fc chimera binding to linaclotide abrogated linaclotide-induced Isc, returning to baseline. Furthermore, linaclotide activation of GC-C induced cGMP secretion from the apical and basolateral membranes of colonic epithelium. MRP4 inhibition blocked cGMP efflux from the apical membrane, but not the basolateral membrane. These data reveal a novel, previously unrecognized mechanism that functionally couples GC-C-induced luminal electrolyte transport and cGMP secretion to spatially restricted, compartmentalized regulation by MRP4 at the apical membrane of intestinal epithelium. These findings have important implications for gastrointestinal disorders with symptoms associated with dysregulated fluid homeostasis, such as irritable bowel syndrome with constipation, chronic idiopathic constipation, and secretory diarrhea. PMID:26216942

  16. Truncated atrial natriuretic peptide (ANP) analogs: relationship between receptor binding and cyclic GMP accumulation

    The authors have shown that cultured bovine aortic smooth muscle (BASM) cells contain high affinity receptor sites for the ANP, auriculin (ANP(4-28)). Furthermore, ANP(4-28) causes cyclic GMP (cGMP) levels to increase in BASM. In the present study, the authors synthesized a series of NH2 and/or COOH truncated ANP(4-28) analogs and examined their ability to compete for 125I-ANP(4-28) binding to BASM and increase cGMP levels. ANP-mediated cGMP responses were reduced when amino acids were deleted from the NH2 and/or COOH termini of ANP(4-28). Removal of the NH2 terminal R, R-S, or R-S-S residues resulted in a 10X decrease in potency for cGMP stimulation. Deletion of the COOH terminal R-Y and F-R-Y residues resulted in a marked decline in potency. ANP's lacking the F-R-Y tripeptide were nearly inactive in stimulating cGMP accumulation. In contrast to the cGMP effects, NH2 and/or COOH truncations of ANP(4-28) did not alter apparent receptor binding affinities (Ki(app)). All of these peptide analogs exhibited Ki(app)'s of 1-5 nM. Furthermore, peptides that bound effectively and failed to elicit cGMP responses did not antagonize ANP(4-28)-mediated cGMP increases. These binding and functional data suggest the presence of a single class of ANP receptors on BASM is insufficient to explain the actions of ANP's in these cells

  17. Modulation by cyclic GMP of the odour sensitivity of vertebrate olfactory receptor cells

    Leinders-Zufall, T.; Shepherd, G. M.; Zufall, F.

    1996-01-01

    Recent evidence has indicated a significant role for the cGMP second messenger system in vertebrate olfactory transduction but no clear functions have been identified for cGMP so far. Here, we have examined the effects of 8-Br-cGMP and carbon monoxide (CO) on odour responses of salamander olfactory receptor neurons using perforated patch recordings. We report that 8-Br-cGMP strongly down-regulates the odour sensitivity of the cells, with a K1/2 of 460 nM. This adaptation-like effect can be mimicked by CO, an activator of soluble guanylyl cyclase, with a K1/2 of 1 microM. Sensitivity modulation is achieved through a regulatory chain of events in which cGMP stimulates a persistent background current due to the activation of cyclic nucleotide-gated channels. This in turn leads to sustained Ca2+ entry providing a negative feedback signal. One consequence of the Ca2+ entry is a shift to the right of the stimulus-response curve and a reduction in saturating odour currents. Together, these two effects can reduce the sensory generator current by up to twenty-fold. Thus, cGMP functions to control the gain of the G-protein coupled cAMP pathway. Another consequence of the action of cGMP is a marked prolongation of the odour response kinetics. The effects of CO/cGMP are long-lasting and can continue for minutes. Hence, we propose that cGMP helps to prevent saturation of the cell's response by adjusting the operational range of the cAMP cascade and contributes to olfactory adaptation by decreasing the sensitivity of olfactory receptor cells to repeated odour stimuli.

  18. A cGMP-signaling pathway in a subset of olfactory sensory neurons

    Meyer, M.R.; Angele, A.; Kremmer, E; Kaupp, U B; F. Müller

    2000-01-01

    It is well established that signal transduction in sensory neurons of the rat olfactory epithelium involves a cAMP-signaling pathway. However, a small number of olfactory neurons specifically express cGMP-signaling components, namely a guanylyl cyclase (GC-D) and a cGMP-stimulated phosphodiesterase (PDE2). Here, we show that this subset of olfactory neurons expressing GC-D and PDE2 does also express the subunit of a cGMP-selective cyclic nucleotide-gated (CNG) channel that has been previously...

  19. Radioimmunoassay for cyclic GMP with femtomole sensitivity using tritiated label and acetylated ligands

    An economical assay using [3H]cyclic GMP is described which will be of use to those laboratories either restricted from using γ isotopes or who do not possess gamma-counting facilities. In this assay, label, standards, and samples are acetylated, and interacted with an antibody raised against the succinyl derivative of cyclic GMP prepared in the usual way. Using this assay procedure 20 fmol of cyclic GMP are detectable. The optimal assay conditions were calculated on theoretical grounds. The use of acetylated ligands might also be applied to the assay of cyclic AMP

  20. GEp/GMp ratio by polarization transfer in e --> p --> ep -->

    The ratio of the proton's elastic electromagnetic form factors, GEp/GMp was obtained by measuring Pi and Pl, the transverse and the longitudinal recoil proton polarization, respectively. For elastic ep to ep, GEp/GMp is proportional to Pt/Pl. Simultaneous measurement of Pt and Pl in a polarimeter provides good control of the systematic uncertainty. The results for the ratio GEp/GMp show a systematic decrease as Q2 increases from 0.5 to 3.5 GeV2, indicating for the first time a definite difference in the spatial distribution of charge and magnetization currents in the proton

  1. GEp/GMp ratio by polarization transfer in ep → ep

    The ratio of the proton's elastic electromagnetic form factors, GEp/GMp was obtained by measuring Pt and P(ell), the transverse and the longitudinal recoil proton polarization, respectively. For elastic ep → ep, GEp/GMp is proportional to Pt/P(ell). Simultaneous measurement of Pt and P(ell) in a polarimeter provides good control of the systematic uncertainty. The results for the ratio GEp/GMp show a systematic decrease as Q2 increases from 0.5 to 3.5 GeV2, indicating for the first time a definite difference in the spatial distribution of charge and magnetization currents in the proton

  2. Pathophysiology of Hypertension in the Absence of Nitric Oxide/Cyclic GMP Signaling

    Thoonen, Robrecht; Sips, Patrick; Bloch, Kenneth Daniel; Buys, Emmanuel

    2012-01-01

    The nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling system is a well-characterized modulator of cardiovascular function, in general, and blood pressure, in particular. The availability of mice mutant for key enzymes in the NO-cGMP signaling system facilitated the identification of interactions with other blood pressure modifying pathways (e.g. the renin-angiotensin-aldosterone system) and of gender-specific effects of impaired NO-cGMP signaling. In addition, recent genome-wi...

  3. Mechanism of activation of bacterial cellulose synthase by cyclic-di-GMP

    Morgan, Jacob L.W.; McNamara, Joshua T.; Zimmer, Jochen

    2014-01-01

    The bacterial signaling molecule cyclic-di-GMP stimulates the synthesis of bacterial cellulose, frequently found in biofilms. Bacterial cellulose is synthesized and translocated across the inner membrane by a complex of the cellulose synthase BcsA and BcsB subunits. Here we present crystal structures of the cyclic-di-GMP-activated BcsA–B complex. The structures reveal that cyclic-di-GMP releases an auto-inhibited state of the enzyme by breaking a salt bridge which otherwise tethers a conserve...

  4. A calcium-permeable cGMP-activated cation conductance in hippocampal neurons

    Leinders-Zufall, T.; Rosenboom, H.; Barnstable, C. J.; Shepherd, G. M.; Zufall, F.

    1995-01-01

    Whole-cell patch clamp recordings detected a previously unidentified cGMP-activated membrane conductance in cultured rat hippocampal neurons. This conductance is nonselectively permeable for cations and is completely but reversibly blocked by external Cd2+. The Ca2+ permeability of the hippocampal cGMP-activated conductance was examined in detail, indicating that the underlying ion channels display a high relative permeability for Ca2+. The results indicate that hippocampal neurons contain a cGMP-activated membrane conductance that has some properties similar to the cyclic nucleotide-gated channels previously shown in sensory receptor cells and retinal neurons. In hippocampal neurons this conductance similarly could mediate membrane depolarization and Ca2+ fluxes in response to intracellular cGMP elevation.

  5. Determination of reactivity of M-cholinergic receptor/cGMP system of peripheral lymphocytes

    Lymphocytes were separated from peripheral blood and incubated in Hanks' solution with calcium or buffer solution containing phosphodiesterase inhibitor IBMX. When carbachol at 1-10 mmol/L was added to the incubation medium, the intracellular cGMP content as determined by high-sensitivity RIA was elevated by 66%-80%. Such an elevation could be blocked by atropine and hence is a specific reaction mediated through M-receptors. A method based on this reaction was thus established to reflect the reactivity of M-receptor/cGMP system. Preliminary experiment revealed that the base level of lymphocyte cGMP as well as the elevation of cGMP induced by carbachol in aged (24-26 months old) rats were significantly lower than young rats. The methodology, especially the influence of incubation conditions was discussed

  6. The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation

    Kruuse, Christina; Rybalkin, S D; Khurana, T S; Jansen-Olesen, I; Olesen, J.; Edvinsson, L

    2001-01-01

    The aim was to investigate the presence and activity of cGMP hydrolysing phosphodiesterases in guinea pig basilar arteries and the effect of selective and non-selective phosphodiesterase inhibitors on cerebral artery dilatation involving the nitric oxide (NO)-guanosine cyclic 3'5-monophosphate (cGMP......M) pretreatment, indicating a close relation to the nitric oxide-cGMP pathway. The responses to zaprinast and dipyridamole, however, were not only moderately affected, but also restored by sodium nitroprusside (0.1 microM) pretreatment. At high concentrations, the dilatory effects of zaprinast and dipyridamole...... were partly caused by cGMP-independent mechanisms. Targeting the phosphodiesterases present in cerebral arteries, with selective inhibitors or activators of phosphodiesterase, may be a possible new way of treating cerebrovascular disease....

  7. Compilation of key GMP requirements in us and Japan for Tablet Manufacturing

    Sujith Kumar . M

    2011-12-01

    Full Text Available The tablet is most popular dosage form in the world. The objective of this work helps in bringing the awareness about the manufacturing requirements as per USFDA and Japan. GMP covers all aspects of production, from the starting materials, premises, equipment and training and personal hygiene to staff. GMP of tablet manufacturing was designed to ensure that all is well. Implementation of GMP is an investment in good quality medicines. It demonstrates industry and regulatory authority’s support for an effective pharmaceutical quality system to enhance the quality and availability of medicines around the world in the interest of public health. Implementation of GMP throughout the product lifecycle should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities. It also helps in increasing the process efficiency and product quality by adopting the current, risk-based manufacturing approach and in turn optimizes manufacturing process and improves quality of the end-product.

  8. Preparation of 2'-O-succinyl[8-3H]cGMP and of 2'-O-([2,3-3H]succinyl)cGMP

    The methods are described of the preparation of 2'-O-succinyl[8-3H]cGMP of a molar activity of 416 GBq mmol-1 and 2'-O-([2,3-3H]succinyl)cGMP of a molar activity of 1.722 TBq mmol-1. In tracer tests the effect was studied of molar concentration of succinic anhydride on reaction yield. Also identified were reaction conditions under which the isotopic exchange of tritium in [8-3H]cGMP is limited [2,3-3H]succinic anhydride was prepared by tritiation of maleinic anhydride in anhydrous dioxane catalyzed by 10% Pd/C. (author). 1 fig., 7 tabs., 6 refs

  9. Addendum to papers from the GANIL (Grand Accelerateur National d'Ions Lourds) GANISOL Team, published in Proceedings of the 13th International Conference on Ion Sources, Gatlinburg, Tennessee, September 2009

    This addendum applies to the paper authored by contributors from the Grand Accelerateur National d'Ions Lourds (GANIL) published in the February 2010 issue of Review of Scientific Instruments, within the Proceedings of the 13th International Conference on Ion Sources, Gatlinburg, Tennessee, September 2009 (Key Scientific coordinator: P. Delahaye; Technical coordinator: P. Jardin; SPIRAL 2 coordinator: R. Leroy and H. Fraanberg-Delahaye; GPI leader: P. Leherissier; and Direction correspondant: P. Roussel-Chomaz). This addendum provides the full list of GANISOL contributors and their affiliations.

  10. Expression and Genetic Activation of Cyclic Di-GMP-Specific Phosphodiesterases in Escherichia coli

    Reinders, Alberto; Hee, Chee-Seng; Ozaki, Shogo; Mazur, Adam; Boehm, Alex; Schirmer, Tilman

    2015-01-01

    ABSTRACT Intracellular levels of the bacterial second messenger cyclic di-GMP (c-di-GMP) are controlled by antagonistic activities of diguanylate cyclases and phosphodiesterases. The phosphodiesterase PdeH was identified as a key regulator of motility in Escherichia coli, while deletions of any of the other 12 genes encoding potential phosphodiesterases did not interfere with motility. To analyze the roles of E. coli phosphodiesterases, we demonstrated that most of these proteins are expressed under laboratory conditions. We next isolated suppressor mutations in six phosphodiesterase genes, which reinstate motility in the absence of PdeH by reducing cellular levels of c-di-GMP. Expression of all mutant alleles also led to a reduction of biofilm formation. Thus, all of these proteins are bona fide phosphodiesterases that are capable of interfering with different c-di-GMP-responsive output systems by affecting the global c-di-GMP pool. This argues that E. coli possesses several phosphodiesterases that are inactive under laboratory conditions because they lack appropriate input signals. Finally, one of these phosphodiesterases, PdeL, was studied in more detail. We demonstrated that this protein acts as a transcription factor to control its own expression. Motile suppressor alleles led to a strong increase of PdeL activity and elevated pdeL transcription, suggesting that enzymatic activity and transcriptional control are coupled. In agreement with this, we showed that overall cellular levels of c-di-GMP control pdeL transcription and that this control depends on PdeL itself. We thus propose that PdeL acts both as an enzyme and as a c-di-GMP sensor to couple transcriptional activity to the c-di-GMP status of the cell. IMPORTANCE Most bacteria possess multiple diguanylate cyclases and phosphodiesterases. Genetic studies have proposed that these enzymes show signaling specificity by contributing to distinct cellular processes without much cross talk. Thus, spatial

  11. Clinical relevance of cyclic GMP modulators: A translational success story of network pharmacology.

    Oettrich, J M; Dao, V T; Frijhoff, J; Kleikers, Pwm; Casas, A I; Hobbs, A J; Schmidt, Hhhw

    2016-04-01

    Therapies that modulate cyclic guanosine-3'-5'-monophosphate (cGMP) have emerged as one of the most successful areas in recent drug discovery and clinical pharmacology. Historically, their focus has been on cardiovascular disease phenotypes; however, cGMP's relevance is likely to go beyond this rather limited organ-based set of indications. Moreover, the multitude of targets and their apparent interchangeability is a proof-of-concept of network pharmacology. PMID:26765222

  12. Discrete cyclic di-GMP-dependent control of bacterial predation versus axenic growth in Bdellovibrio bacteriovorus

    Laura Hobley; Fung, Rowena K. Y.; Carey Lambert; Maximilian A T S Harris; Dabhi, Jayesh M.; King, Simon S.; Basford, Sarah M; Kaoru Uchida; Robert Till; Rashidah Ahmad; Shin-Ichi Aizawa; Mark Gomelsky; R Elizabeth Sockett

    2012-01-01

    Bdellovibrio bacteriovorus is a Delta-proteobacterium that oscillates between free-living growth and predation on Gram-negative bacteria including important pathogens of man, animals and plants. After entering the prey periplasm, killing the prey and replicating inside the prey bdelloplast, several motile B. bacteriovorus progeny cells emerge. The B. bacteriovorus HD100 genome encodes numerous proteins predicted to be involved in signalling via the secondary messenger cyclic di-GMP (c-di-GMP)...

  13. Design of GMP compliance radiopharmaceutical production facility in MINT

    Full text: In 1985, MINT built the only radiopharmaceutical production facility in Malaysia. The facility was designed based on IAEA (International Atomic Energy Agency) standard guidelines, which provides radiation safety to the operator and the surrounding environment from radioactive contamination. In 1999, BPFK (Malaysia National Pharmaceutical Control Bureau) enforced the guidelines from Pharmaceutical Inspection Convention Scheme (PICS) to meet the requirements of the Good Manufacturing Practice (GMP) for Pharmaceutical Products. Among others, the guidelines require the pharmaceutical production facility to be designed based on cleanroom environment. In order to meet this requirement, the design of a radiopharmaceutical production facility shall combine the concept of radiation safety and cleanroom to ensure that both requirements from GMP and IAEA are met. This design requirement is necessary to ensure a radiopharmaceutical production facility which is safe, has high production quality and in compliance with the Malaysian and International standards. In order to obtain the license to continue producing radiopharmaceutical products, MINT shall closely follow the guidelines from PICS: GMP and nuclear facility requirements. To meet those requirements, the layout of MINT facility was redesigned to ensure the contaminants or particulates from outside area will not enter the production area. The flow path of personnel to the production room is equiped with air lock and change room in order to avoid contamination from outside environment. The airlock and changing room provide the physical separation of different stages of cleanroom class and between clean area and non-clean area. The cleanliness level or class for each room is determined by the criticality of exposure of the process and products to the environment. The clean class which is grade A is used for critical process and the other grade is for non-critical process or as a background. The concepts of

  14. CPT-cGMP Is A New Ligand of Epithelial Sodium Channels.

    Ji, Hong-Long; Nie, Hong-Guang; Chang, Yongchang; Lian, Qizhou; Liu, Shan-Lu

    2016-01-01

    Epithelial sodium channels (ENaC) are localized at the apical membrane of the epithelium, and are responsible for salt and fluid reabsorption. Renal ENaC takes up salt, thereby controlling salt content in serum. Loss-of-function ENaC mutations lead to low blood pressure due to salt-wasting, while gain-of-function mutations cause impaired sodium excretion and subsequent hypertension as well as hypokalemia. ENaC activity is regulated by intracellular and extracellular signals, including hormones, neurotransmitters, protein kinases, and small compounds. Cyclic nucleotides are broadly involved in stimulating protein kinase A and protein kinase G signaling pathways, and, surprisingly, also appear to have a role in regulating ENaC. Increasing evidence suggests that the cGMP analog, CPT-cGMP, activates αβγ-ENaC activity reversibly through an extracellular pathway in a dose-dependent manner. Furthermore, the parachlorophenylthio moiety and ribose 2'-hydroxy group of CPT-cGMP are essential for facilitating the opening of ENaC channels by this compound. Serving as an extracellular ligand, CPT-cGMP eliminates sodium self-inhibition, which is a novel mechanism for stimulating salt reabsorption in parallel to the traditional NO/cGMP/PKG signal pathway. In conclusion, ENaC may be a druggable target for CPT-cGMP, leading to treatments for kidney malfunctions in salt reabsorption. PMID:27019621

  15. Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers.

    Hengge, Regine; Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat

    2016-01-01

    The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany)brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i)c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology,with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111

  16. The Nitric Oxide/Cyclic GMP Pathway in Organ Transplantation: Critical Role in Successful Lung Preservation

    Pinsky, David J.; Naka, Yoshifumi; Chowdhury, Nepal C.; Liao, Hui; Oz, Mehmet C.; Michler, Robert E.; Kubaszewski, Eugeniusz; Malinski, Tadeusz; Stern, David M.

    1994-12-01

    Reestablishment of vascular homeostasis following ex vivo preservation is a critical determinant of successful organ transplantation. Because the nitric oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial interactions, we hypothesized that reactive oxygen intermediates would lead to decreased NO (and hence cGMP) levels following pulmonary reperfusion, leading to increased pulmonary vascular resistance and leukostasis. Using an orthotopic rat model of lung transplantation, a porphyrinic microsensor was used to make direct in vivo measurements of pulmonary NO. NO levels measured at the surface of the transplanted lung plummeted immediately upon reperfusion, with levels moderately increased by topical application of superoxide dismutase. Because cGMP levels declined in preserved lungs after reperfusion, this led us to buttress the NO pathway by adding a membrane-permeant cGMP analog to the preservation solution. Compared with grafts stored in its absence, grafts stored with supplemental 8-Br-cGMP and evaluated 30 min after reperfusion demonstrated lower pulmonary vascular resistances with increased graft blood flow, improved arterial oxygenation, decreased neutrophil infiltration, and improved recipient survival. These beneficial effects were dose dependent, mimicked by the type V phosphodiesterase inhibitor 2-o-propoxyphenyl-8-azapurin-6-one, and inhibited by a cGMP-dependent protein kinase antagonist, the R isomer of 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate. Augmenting the NO pathway at the level of cGMP improves graft function and recipient survival following lung transplantation.

  17. NO, nitrotyrosine, and cyclic GMP in signal transduction

    Hanafy, K. A.; Krumenacker, J. S.; Murad, F.

    2001-01-01

    Over the past 25 years, the role of nitric oxide (NO) in biology has evolved from being recognized as an environmental pollutant to an endogenously produced substance involved in cell communication and signal transduction. NO is produced by a family of enzymes called nitric oxide synthases (NOSs), which can be stimulated by a variety of factors that mediate responses to various stimuli. NO can initiate its biological effects through activation of the heterodimeric enzyme, soluble guanylyl cyclase (sGC), or through several other chemical reactions. Activation of sGC results in the production of 3',5'-cyclic guanosine monophosphate (cGMP), an intracellular second messenger signaling molecule, which can subsequently mediate such diverse physiological events such as vasodilatation and immunomodulation. Chemically reactive NO can affect physiological changes through modifications to cellular proteins, one of which is tyrosine nitration. The demonstration that NO is involved in so many biological pathways indicates the importance of this endogenously produced substance, and suggests that there is much more to be discovered about its role in biology in years to come.

  18. In Vivo Reconstitution of the Negative Feedback in Nitric Oxide/cGMP Signaling: Role of Phosphodiesterase Type 5 Phosphorylation

    Mullershausen, Florian; Russwurm, Michael; Koesling, Doris; Friebe, Andreas

    2004-01-01

    Most effects of the messenger molecule nitric oxide (NO) are mediated by cGMP, which is formed by NO-sensitive guanylyl cyclase (GC) and degraded by phosphodiesterases (PDEs). In platelets, NO elicits a spike-like cGMP response and causes a sustained desensitization. Both characteristics have been attributed to PDE5 activation caused by cGMP binding to its regulatory GAF domain. Activation is paralleled by phosphorylation whose precise function remains unknown. Here, we report reconstitution ...

  19. Structural and Biochemical Determinants of Ligand Binding by the c-di-GMP Riboswitch

    The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that the most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 (angstrom)) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3(prime)-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.

  20. A Cyclic GMP-Dependent K+ Channel in the Blastocladiomycete Fungus Blastocladiella emersonii.

    Avelar, Gabriela Mól; Glaser, Talita; Leonard, Guy; Richards, Thomas A; Ulrich, Henning; Gomes, Suely L

    2015-09-01

    Phototaxis in flagellated zoospores of the aquatic fungus Blastocladiella emersonii depends on a novel photosensor, Blastocladiella emersonii GC1 (BeGC1), comprising a type I (microbial) rhodopsin fused to a guanylyl cyclase catalytic domain, that produces the conserved second messenger cyclic GMP (cGMP). The rapid and transient increase in cGMP levels during the exposure of zoospores to green light was shown to be necessary for phototaxis and dependent on both rhodopsin function and guanylyl cyclase activity. It is noteworthy that BeGC1 was localized to the zoospore eyespot apparatus, in agreement with its role in the phototactic response. A putative cyclic nucleotide-gated channel (BeCNG1) was also identified in the genome of the fungus and was implicated in flagellar beating via the action of a specific inhibitor (l-cis-diltiazem) that compromised zoospore motility. Here we show that B. emersonii expresses a K(+) channel that is activated by cGMP. The use of specific channel inhibitors confirmed the activation of the channel by cGMP and its K(+) selectivity. These characteristics are consistent with the function of an ion channel encoded by the BeCNG1 gene. Other blastocladiomycete fungi, such as Allomyces macrogynus and Catenaria anguillulae, possess genes encoding a similar K(+) channel and the rhodopsin-guanylyl cyclase fusion protein, while the genes encoding both these proteins are absent in nonflagellated fungi. The presence of these genes as a pair seems to be an exclusive feature of blastocladiomycete fungi. Taken together, these data demonstrate that the B. emersonii cGMP-activated K(+) channel is involved in the control of zoospore motility, most probably participating in the cGMP-signaling pathway for the phototactic response of the fungus. PMID:26150416

  1. Cyclic di-GMP stimulates biofilm formation and inhibits virulence of Francisella novicida.

    Zogaj, Xhavit; Wyatt, Geoff C; Klose, Karl E

    2012-12-01

    Francisella tularensis is a gram-negative bacterium that is highly virulent in humans, causing the disease tularemia. F. novicida is closely related to F. tularensis and exhibits high virulence in mice, but it is avirulent in healthy humans. An F. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE-encoding protein genes are present in the F. tularensis genome. F. novicida strains lacking either the two DGC/PDE genes (cdgA and cdgB) or the entire gene cluster (strain KKF457) are defective for biofilm formation. In addition, expression of CdgB or a heterologous DGC in strain KKF457 stimulated F. novicida biofilms, even in a strain lacking the biofilm regulator QseB. Genetic evidence suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC. The F. novicida qseB strain showed reduced cdgA and cdgB transcript levels, demonstrating an F. novicida biofilm signaling cascade that controls cdGMP levels. Interestingly, KKF457 with elevated cdGMP levels exhibited a decrease in intramacrophage replication and virulence in mice, as well as increased growth yields and biofilm formation in vitro. Microarray analyses revealed that cdGMP stimulated the transcription of a chitinase (ChiB) known to contribute to biofilm formation. Our results indicate that elevated cdGMP in F. novicida stimulates biofilm formation and inhibits virulence. We suggest that differences in human virulence between F. novicida and F. tularensis may be due in part to the absence of cdGMP signaling in F. tularensis. PMID:22988021

  2. Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain.

    Wang, Yu-Chuan; Chin, Ko-Hsin; Tu, Zhi-Le; He, Jin; Jones, Christopher J; Sanchez, David Zamorano; Yildiz, Fitnat H; Galperin, Michael Y; Chou, Shan-Ho

    2016-01-01

    C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date. PMID:27578558

  3. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

    Carvalho-Costa, P.G. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Branco, L.G.S. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Leite-Panissi, C.R.A. [Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-09-19

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.

  4. Effects of radioprotectors on the cAMP and cGMP systems

    The sulphur-containing radioprotectors mercaptoethylamine (MEA), aminoethylisothiourea (AET), 2-aminothiazoline, 4-oxo-2-amino-thiazoline, and S-S-oxapentane-1,5-diisorthiourea, and the radioprotective biogenic amines serotonin, histamine, and dopamine, caused the elevation of cAMP content and intensified the rate of cAMP-dependent protein phosphorylation in tissues of animals following intraperitoneal injection at radioprotective doses. Biogenic amines stimulated the adenylate cyclase activity in membrane preparations from liver, spleen, and small-intestine mucosa; sulphur-containing radioprotectors caused no such effects. None of the radioprotectors affected CAMP and cGMP phosphodiesterases in vitro. AET and MEA inhibited guanylate cyclase in vitro, whereas serotonin and dopamine stimulated the enzyme. A biphasic change in the level of cGMP was observed in tissues after the administration of MEA and AET (more than 2-fold fally by 1-3 min after the administration of drug and 1.4-fold rise after 15-20 min); serotonin and dopamine caused a slow rise in the cGMP level, the cAMP/cGMP ratio in liver showed biphasic changes in level during the 20 min following injection of serotonin. The data obtained support the conclusion that the action of radioprotectors on cellular metabolism in animals may be mediated by the cAMP system.The reciprocal regulation of radioresistance by cAMP and cGMP is unlikely to exist. (orig.)

  5. Inhibition of cGMP-dependent protein kinase by (Rp)-guanosine 3',5'-monophosphorothioates.

    Butt, E; van Bemmelen, M; Fischer, L; Walter, U; Jastorff, B

    1990-04-01

    The activation of the cGMP-dependent protein kinase and cAMP-dependent protein kinase by the diastereomers of guanosine 3',5'-monophosphorothioate, (Sp)-cGMPS and (Rp)-cGMPS, and 8-chloroguanosine 3',5'-monophosphorothioate, (Sp)-8-Cl-cGMPS and (Rp)-8-Cl-cGMPS, was investigated using the peptide Kemptide as substrate. The (Sp)-diastereomers, which have an axial exocyclic sulfur atom, bound to the cGMP-dependent protein kinase and stimulated its phosphotransferase activity. In contrast, the (Rp)-isomers, which have an equatorial exocyclic sulfur atom, bound to the enzyme without stimulation of its activity. (Rp)-cGMPS and (Rp)-8-Cl-cGMPS antagonized the activation of the cGMP-dependent protein kinase with a Ki of 20 microM and 1.5 microM, respectively. (Rp)-cGMPS also antagonized the activation of cAMP-dependent protein kinase with a Ki of 20 microM. In contrast, (Rp)-8-cGMPS ws a weak inhibitor of the cAMP-dependent protein kinase with a Ki of 100 microM. (Rp)-8-Cl-cGMPS appears to be a rather selective inhibitor of the cGMP-dependent protein kinase and may be a useful tool for studying the role of cGMP in broken and intact cell systems. PMID:2158906

  6. Bacterial c-di-GMP Affects Hematopoietic Stem/Progenitors and Their Niches through STING

    Hiroshi Kobayashi

    2015-04-01

    Full Text Available Upon systemic bacterial infection, hematopoietic stem and progenitor cells (HSPCs migrate to the periphery in order to supply a sufficient number of immune cells. Although pathogen-associated molecular patterns reportedly mediate HSPC activation, how HSPCs detect pathogen invasion in vivo remains elusive. Bacteria use the second messenger bis-(3′-5′-cyclic dimeric guanosine monophosphate (c-di-GMP for a variety of activities. Here, we report that c-di-GMP comprehensively regulated both HSPCs and their niche cells through an innate immune sensor, STING, thereby inducing entry into the cell cycle and mobilization of HSPCs while decreasing the number and repopulation capacity of long-term hematopoietic stem cells. Furthermore, we show that type I interferon acted as a downstream target of c-di-GMP to inhibit HSPC expansion in the spleen, while transforming growth factor-β was required for c-di-GMP-dependent splenic HSPC expansion. Our results define machinery underlying the dynamic regulation of HSPCs and their niches during bacterial infection through c-di-GMP/STING signaling.

  7. Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

    Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress

  8. Auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism

    Cai, Weiming; Hu, Liwei; Hu, Xiangyang; Cui, Dayong; Cai, Weiming

    Gravitropism is the asymmetric growth or curvature of plant organs in response to gravistimulation. There is a complex signal transduction cascade which involved in the differential growth of plants in response to changes in the gravity vector. The role of auxin in gravitropism has been demonstrated by many experiments, but little is known regarding the molecular details of such effects. In our studies before, mediation of the gravitropic bending of soybean roots and rice leaf sheath bases by nitric oxide, cGMP and gibberellins, are induced by auxin. The asymmetrical distribution of nitric oxide, cGMP and gibberellins resulted from the asymmetrical synthesis of them in bending sites. In soybean roots, inhibitions of NO and cGMP synthesis reduced differential NO and cGMP accumulation respectively, which both of these effects can lead to the reduction of gravitropic bending. Gibberellin-induced OsXET, OsEXPA4 and OsRWC3 were also found involved in the gravitropic bending. These data indicated that auxin-induced nitric oxide, cGMP and gibberellins were involved in the gravitropism. More experiments need to prove the more detailed mechanism of them.

  9. Differential modulation of the glutamate-nitric oxide-cyclic GMP pathway by distinct neurosteroids in cerebellum in vivo.

    Cauli, O; González-Usano, A; Agustí, A; Felipo, V

    2011-09-01

    The glutamate-nitric oxide (NO)-cGMP pathway mediates many responses to activation of N-methyl-d-aspartate (NMDA) receptors, including modulation of some types of learning and memory. The glutamate-NO-cGMP pathway is modulated by GABAergic neurotransmission. Activation of GABA(A) receptors reduces the function of the pathway. Several neurosteroids modulate the activity of GABA(A) and/or NMDA receptors, suggesting that they could modulate the function of the glutamate-NO-cGMP pathway. The aim of this work was to assess, by in vivo microdialysis, the effects of several neurosteroids with different effects on GABA(A) and NMDA receptors on the function of the glutamate-NO-cGMP pathway in cerebellum in vivo. To assess the effects of the neurosteroids on the glutamate-NO-cGMP pathway, they were administered through the microdialysis probe before administration of NMDA and the effects on NMDA-induced increase in extracellular cGMP were analyzed. We also assessed the effects of the neurosteroids on basal levels of extracellular cGMP. To assess the effects of neurosteroids on nitric oxide synthase (NOS) activity and on NMDA-induced activation of NOS, we also measured the effects of the neurosteroids on extracellular citrulline. Pregnanolone and tetrahydrodeoxy-corticosterone (THDOC) behave as agonists of GABA(A) receptors and completely block NMDA-induced increase in cGMP. Pregnanolone but not THDOC also reduced basal levels of extracellular cGMP. Pregnenolone did not affect extracellular cGMP or its increase by NMDA administration. Pregnenolone sulfate increased basal extracellular cGMP and potentiated NMDA-induced increase in cGMP, behaving as an enhancer of NMDA receptors activation. Allopregnanolone and dehydroepiandrosterone sulphate behave as antagonists of NMDA receptors, increasing basal cGMP and blocking completely NMDA-induced increase in cGMP. Dehydroepiandrosterone sulphate seems to do this by activating sigma receptors. These data support the concept that, at

  10. Regulation of biofilm formation and cellular buoyancy through modulating intracellular cyclic di-GMP levels in engineered cyanobacteria.

    Agostoni, Marco; Waters, Christopher M; Montgomery, Beronda L

    2016-02-01

    The second messenger cyclic dimeric (3'→5') GMP (cyclic di-GMP or c-di-GMP) has been implicated in the transition between motile and sessile lifestyles in bacteria. In this study, we demonstrate that biofilm formation, cellular aggregation or flocculation, and cellular buoyancy are under the control of c-di-GMP in Synechocystis sp. PCC 6803 (Synechocystis) and Fremyella diplosiphon. Synechocystis is a unicellular cyanobacterium and displays lower levels of c-di-GMP; F. diplosiphon is filamentous and displays higher intracellular c-di-GMP levels. We transformed Synechocystis and F. diplosiphon with a plasmid for constitutive expression of genes encoding diguanylate cylase (DGC) and phosphodiesterase (PDE) proteins from Vibrio cholerae or Escherichia coli, respectively. These engineered strains allowed us to modulate intracellular c-di-GMP levels. Biofilm formation and cellular deposition were induced in the DGC-expressing Synechocystis strain which exhibited high intracellular levels of c-di-GMP; whereas strains expressing PDE in Synechocystis and F. diplosiphon to drive low intracellular levels of c-di-GMP exhibited enhanced cellular buoyancy. In addition, the PDE-expressing F. diplosiphon strain showed elevated chlorophyll levels. These results imply roles for coordinating c-di-GMP homeostasis in regulating native cyanobacterial phenotypes. Engineering exogenous DGC or PDE proteins to regulate intracellular c-di-GMP levels represents an effective tool for uncovering cryptic phenotypes or modulating phenotypes in cyanobacteria for practical applications in biotechnology applicable in photobioreactors and in green biotechnologies, such as energy-efficient harvesting of cellular biomass or the treatment of metal-containing wastewaters. PMID:26192200

  11. Nutrition at school: preparing for the future. The Thirteenth Annual Nutrition Symposium.

    1994-01-01

    Two of the best ways to improve the quality of childhood nutrition are (a) more collaboration at the national, State, and local levels and (b) adoption of innovative and multimedia learning methods, according to the leaders of nutrition education. These themes were discussed at the 13th Annual Nutrition Symposium, which was held March 9, 1994, in Washington, DC. In recognition of National Nutrition Month, a collaborative effort of the Public Health Service's Office of Disease Prevention and H...

  12. 国际钨协第13届年会市场报告%A Market Report for the 13th Annual General Meeting of International Tungsten Industry Association

    Maby,M; 邱银兰

    2000-01-01

    @@ 0 前言 本报告是为在美国华盛顿召开的国际钨协第13届年度大会准备的,内备有最新统计数据(截止2000年6月)对原钨的供应和需求进行了评估.所有的数据均以钨含量为单位.感谢所有提供有关统计数据和资料的会员们的合作,特别是感谢欧洲金属协会和美国地质调查局给予的支持和帮助.

  13. Perspectives on the Economy and Monetary Policy The 13th Annual Economic Outlook The School of Business at La Salle University, Union League of Philadelphia Business Network, January 14, 2014, Philadelphia, PA

    Charles I. Plosser

    2014-01-01

    Presented by Charles I. Plosser, President and Chief Executive Officer, Federal Reserve Bank of Philadelphia The School of Business at La Salle University, Union League of Philadelphia Business Network, January 14, 2014, Philadelphia, PA President Plosser discusses his forecast for growth, prospects for the labor market, and inflation expectations, as well as the extraordinary policy actions the Federal Reserve has taken to support economic recovery. He will also speak about the history of th...

  14. Role of nitric oxide and cyclic GMP signaling in melanocyte response to hypergravity

    Ivanova, Krassimira; Lambers, Britta; Tsiockas, Wasiliki; Block, Ingrid; Gerzer, Rupert

    Nitric oxide (NO) has a prominent role in many (patho)physiological processes in the skin including erythema, inflammation, and cancerogenesis. The soluble guanylyl cyclase (sGC), a key transducer in NO signaling, catalyzes the formation of the second messenger guanosine 3´,5´-cyclic monophosphate (cyclic cGMP or cGMP). For human melanocytes, which are responsible for skin pigmentation by synthesizing the pigment melanin, it has been reported that the NO/sGC/cGMP pathway is involved in UVB-induced melanogenesis. Melanin acts as a scavenger for free radicals that may arise during metabolic stress. It may also act as a photosensitizer that generates active oxygen species upon UV irradiation, which may initiate hypopigmentary disorders (e.g., vitiligo) as well as UV-induced oncogene cell transformation. In addition, melanoma, a deadly skin cancer, which arises from transformed melanocytes, is characterized by a resistance to chemotherapy. In our studies we have shown that NO can induce perturbation of melanocyte-extracellular matrix component interactions, which may contribute to loss of melanocytes or melanoma metastasis. Such NO effects appear to be modulated partly via cGMP. Moreover, we found that different guanylyl cyclase isoforms are responsible for cGMP synthesis in melanocytic cells. Normal human melanocytes and nonmetastatic melanoma cells predominantly express sGC, which appears to be associated with melanogenesis, whereas absence of NO-sensitive GC, but up-regulated activities of the natriuretic peptide-sensitive membrane guanylyl cyclase isoforms were found in highly metastatic phenotypes. Due to the growing interest in the regulation of signaling activities in normal and transformed cells under altered gravity conditions, we have further investigated whether the NO/cGMP signaling is involved in melanocyte response to gravitational stress. We found that normal human melanocytes and non-metastatic melanoma cell lines, but not highly metastatic cells

  15. Effect of luteinizing hormone on the concentration of cyclic GMP in rabbit ovaries

    It has been shown that luteinizing hormone (LH) causes a rapid increase in cyclic AMP in the ovarian tissue of rabbits which precedes the LH-induced increase in steroidogenesis. Investigations have been made to ascertain the effect of LH on cyclic GMP, using radioimmunoassay techniques. It was found that the concentration of cyclic GMP remained unaffected up to four hours after LH stimulation, but between 4 and 8 hours it was significantly reduced and then returned to the control level. It is suggested that cyclic GMP may have no role in ovarian events in the first few hours after LH treatment. The diminished levels in the later periods may conceivably be related to later effects of LH, such as stimulation of prostaglandin biosynthesis. (U.K.)

  16. Effects of corydalis amabilis Migo total alkaloids on platelet cyclic AMP and cyclic GMP

    Corydalis amabilis Migo total alkaloids (COAMTA), isolated from the root of Corydalis decumbens (Thunb) Pers, possessed inhibitory action on ADP-induced blood platelet aggregation and the formation of thrombus in animal experiments. Its effects on the platelet cyclic AMP and cyclic GMP in incubated rabbit platelet were measured by radioimmunoassay. cAMP was significantly elevated when COAMTA was given 0.08-0.16 mg/ml PRP. In concentration up to 0.16 mg/ml PRP, COAMTA elevated cGMP, but the ratio value of cAMP/cGMP was much higher than that of control group. These results suggest that the anti-platelet activity of COAMTA were mediated through elevation of cAMP levels

  17. Larval Fish Recruitment and Research in the Americas: Proceedings of the Thirteenth Annual Larval Fish Conference Merida, Mexico, 21-26 May 1989

    1991-01-01

    The 13th Annual Larval Fish Conference and Annual Meeting of the American Fisheries Society Early Life History Section cohosted by Mote Marine Laboratory, United States, and the Instituto Nacional de la Pesca, Mexico, were held 21-26 May 1989, in Merida, Yucatan, Mexico. The purpose of holding the meeting in Mexico was to encourage the participation of our Latin American and Caribbean colleagues and to provide a forum for the exchange of ideas and information among researchers working in the ...

  18. Receptors and cGMP signalling mechanism for E. coli enterotoxin in opossum kidney

    Receptors for the heat-stable enterotoxin produced by Escherichia coli were found in the kidney and intestine of the North American opossum and in cultured renal cell lines. The enterotoxin markedly increased guanosine 3',5'-cyclic monophosphate (cGMP) production in slices of kidney cortex and medulla, in suspensions of intestinal mucosa, and in the opossum kidney (OK) and rat kangaroo kidney (PtK-2) cell lines. In contrast, atrial natriuretic factor elicited much smaller increases in cGMP levels of kidney, intestine, or cultured kidney cell lines. The enterotoxin receptors in OK cells had a molecular mass of approximately 120 kDa when measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of receptors crosslinked with 125I-enterotoxin. The occurrence of receptors for the E. coli peptide in OK implies that these receptors may be involved in the regulation of renal tubular function in the opossum. E. coli enterotoxin caused a much larger increase in urine cGMP excretion than did atrial natriuretic factor when these peptides were injected intravenously into opossums. However, atrial natriuretic factor elicited a marked diuresis, natriuresis, and increased urinary excretion of calcium, phosphate, potassium, and magnesium. In contrast, the enterotoxin did not acutely influence OK fluid and electrolyte excretion. Thus the substantial increase in cGMP synthesis produced by the bacterial peptide in OK cortex and medulla in vitro and the increased renal excretion of cGMP in vivo were not associated with changes in electrolyte or water excretion. Whether cGMP represents a second messenger molecule in the kidney is an interesting question that was raised but not answered in this series of experiments

  19. Special section containing papers presented at the 13th IAEA Technical Meeting on Energetic Particles in Magnetic Confinement Systems (Beijing, China, 17-20 September 2013) Special section containing papers presented at the 13th IAEA Technical Meeting on Energetic Particles in Magnetic Confinement Systems (Beijing, China, 17-20 September 2013)

    Lin, Z.

    2014-10-01

    In magnetic fusion plasmas, a significant fraction of the kinetic pressure is contributed by superthermal charged particles produced by auxiliary heating (fast ions and electrons) and fusion reactions (a-particles). Since these energetic particles are often far away from thermal equilibrium due to their non-Maxwellian distribution and steep pressure gradients, the free energy can excite electromagnetic instabilities to intensity levels well above the thermal fluctuations. The resultant electromagnetic turbulence could induce large transport of energetic particles, which could reduce heating efficiency, degrade overall plasma confinement, and damage fusion devices. Therefore, understanding and predicting energetic particle confinement properties are critical to the success of burning plasma experiments such as ITER since the ignition relies on plasma self-heating by a-particles. To promote international exchanges and collaborations on energetic particle physics, the biannual conference series under the auspices of the International Atomic Energy Agency (IAEA) were help in Kyiv (1989), Aspenas (1991), Trieste (1993), Princeton (1995), JET/Abingdon (1997), Naka (1999), Gothenburg (2001), San Diego (2003), Takayama (2005), Kloster Seeon (2007), Kyiv (2009), and Austin (2011). The papers in this special section were presented at the most recent meeting, the 13th IAEA Technical Meeting on Energetic Particles in Magnetic Confinement Systems, which was hosted by the Fusion Simulation Center, Peking University, Beijing, China (17-20 September 2013). The program of the meeting consisted of 71 presentations, including 13 invited talks, 26 oral contributed talks, 30 posters, and 2 summary talks, which were selected by the International Advisory Committee (IAC). The IAC members include H. Berk, L.G. Eriksson, A. Fasoli, W. Heidbrink, Ya. Kolesnichenko, Ph. Lauber, Z. Lin, R. Nazikian, S. Pinches, S. Sharapov, K. Shinohara, K. Toi, G. Vlad, and X.T. Ding. The conference program

  20. EDITORIAL: Invited papers from the 15th International Congress on Plasma Physics combined with the 13th Latin American Workshop on Plasma Physics Invited papers from the 15th International Congress on Plasma Physics combined with the 13th Latin American Workshop on Plasma Physics

    Soto, Leopoldo

    2011-07-01

    The International Advisory Committee of the 15th International Congress on Plasma Physics (ICPP 2010) and the International Advisory Committee of the 13th Latin American Workshop on Plasma Physics (LAWPP 2010) both agreed to hold this combined meeting ICPP-LAWPP-2010 in Santiago de Chile, 8-13 August 2010, considering the celebration of the Bicentennial of Chilean Independence. ICPP-LAWPP-2010 was organized by the Thermonuclear Plasma Department of the Chilean Nuclear Energy Commission (CCHEN) as part of its official program, within the framework of the Chilean Bicentennial activities. This event was also a scientific and academic activity of the project `Center for Research and Applications in Plasma Physics and Pulsed Power, P4', supported by the National Scientific and Technological Commission, CONICYT-Chile, under grant ACT-26. The International Congress on Plasma Physics was first held in Nagoya in 1980, and was followed by: Gothenburg (1982), Lausanne (1984), Kiev (1987), New Delhi (1989), Innsbruck (1992), Foz do Iguacu (1994), Nagoya (1996), Prague (1998), Quebec City (2000), Sydney (2002), Nice (2004), Kiev (2006) and Fukuoka (2008). The purpose of the Congress is to discuss recent progress and outlooks in plasma science, covering fundamental plasma physics, fusion plasmas, astrophysical plasmas, plasma applications, etc. The Latin American Workshop on Plasma Physics was first held in 1982 in Cambuquira, Brazil, followed by: Medellín (1985), Santiago (1988), Buenos Aires (1990), Mexico City (1992), Foz do Iguacu (1994, also combined with ICPP), Caracas (1997), Tandil (1998), La Serena (2000), Sao Pedro (2003), Mexico City (2005) and Caracas (2007). The purpose of the Latin American Workshop on Plasma Physics is to provide a forum in which the achievements of the Latin American plasma physics communities can be displayed, as well as to foster collaboration between plasma scientists within the region and elsewhere. The Program of ICPP-LAWPP-2010 included

  1. Study on design of GMP facility for radio-pharmaceuticals production

    For production and research for practical use of radio-pharmaceuticals using for medical treatment and diagnosis, the complex facility offer shield and clean environment is basically required for protecting personnel from radiation, and protecting the product from contamination. This facility should be designed to comply with GMP(Good Manufacturing Practice). In this study, technical requirements and guide for hot cell and clean room were investigated, and design concept and requirements of facility for radio-pharmaceuticals handling are suggested. And also, GMP facility for production of Tc-99m generator and other radio-pharmaceuticals(Ho-166 etc.) was designed to comply with this design concept and requirements

  2. Discrete cyclic di-GMP-dependent control of bacterial predation versus axenic growth in Bdellovibrio bacteriovorus.

    Laura Hobley

    2012-02-01

    Full Text Available Bdellovibrio bacteriovorus is a Delta-proteobacterium that oscillates between free-living growth and predation on Gram-negative bacteria including important pathogens of man, animals and plants. After entering the prey periplasm, killing the prey and replicating inside the prey bdelloplast, several motile B. bacteriovorus progeny cells emerge. The B. bacteriovorus HD100 genome encodes numerous proteins predicted to be involved in signalling via the secondary messenger cyclic di-GMP (c-di-GMP, which is known to affect bacterial lifestyle choices. We investigated the role of c-di-GMP signalling in B. bacteriovorus, focussing on the five GGDEF domain proteins that are predicted to function as diguanylyl cyclases initiating c-di-GMP signalling cascades. Inactivation of individual GGDEF domain genes resulted in remarkably distinct phenotypes. Deletion of dgcB (Bd0742 resulted in a predation impaired, obligately axenic mutant, while deletion of dgcC (Bd1434 resulted in the opposite, obligately predatory mutant. Deletion of dgcA (Bd0367 abolished gliding motility, producing bacteria capable of predatory invasion but unable to leave the exhausted prey. Complementation was achieved with wild type dgc genes, but not with GGAAF versions. Deletion of cdgA (Bd3125 substantially slowed predation; this was restored by wild type complementation. Deletion of dgcD (Bd3766 had no observable phenotype. In vitro assays showed that DgcA, DgcB, and DgcC were diguanylyl cyclases. CdgA lacks enzymatic activity but functions as a c-di-GMP receptor apparently in the DgcB pathway. Activity of DgcD was not detected. Deletion of DgcA strongly decreased the extractable c-di-GMP content of axenic Bdellovibrio cells. We show that c-di-GMP signalling pathways are essential for both the free-living and predatory lifestyles of B. bacteriovorus and that obligately predatory dgcC- can be made lacking a propensity to survive without predation of bacterial pathogens and thus possibly

  3. Cyclic Di-GMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicida

    Zogaj, Xhavit; Wyatt, Geoff C.; Klose, Karl E.

    2012-01-01

    Francisella tularensis is a Gram-negative bacterium that is highly virulent in humans, causing the disease tularemia. F. novicida is closely related to F. tularensis and exhibits high virulence in mice, but it is avirulent in healthy humans. An F. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE-encoding protein genes a...

  4. Biophysical Techniques for Detection of cAMP and cGMP in Living Cells

    Viacheslav O. Nikolaev

    2013-04-01

    Full Text Available Cyclic nucleotides cAMP and cGMP are ubiquitous second messengers which regulate myriads of functions in virtually all eukaryotic cells. Their intracellular effects are often mediated via discrete subcellular signaling microdomains. In this review, we will discuss state-of-the-art techniques to measure cAMP and cGMP in biological samples with a particular focus on live cell imaging approaches, which allow their detection with high temporal and spatial resolution in living cells and tissues. Finally, we will describe how these techniques can be applied to the analysis of second messenger dynamics in subcellular signaling microdomains.

  5. Polymerization of wheat gluten and the changes of glutenin macropolymer (GMP) during the production of Chinese steamed bread.

    Wang, Xiang-Yu; Guo, Xiao-Na; Zhu, Ke-Xue

    2016-06-15

    Polymerization of gluten and the changes of glutenin macropolymer (GMP) during the production of Chinese steamed bread (CSB) were investigated, providing a theoretical basis to improve and regulate the quality of CSB. Protein extractability and free sulfhydryl (SH) contents increased to some degree during the dough preparation stage, but significantly (PSDS-PAGE) patterns. The microstructure study of the gas cell and the protein network by confocal laser scanning microscopy (CLSM) further revealed the formation of a continuous and three-dimensional gluten network. The loss and recovery of GMP wet weight during dough processing were significant (P<0.05). Glutenin depolymerization negatively correlated with GMP wet weight and the contents of high molecular weight glutenin subunits (HMW-GS) and low molecular weight glutenin subunits (LMW-GS). Gluten polymerization led to a decrease in G' and G″ of GMP while gluten depolymerization induced a slight recovery in G' and G″ of GMP. PMID:26868577

  6. Studies on the interactions between the cyclic nucleotide-binding sites of cGMP-dependent protein kinase

    The rate and equilibrium kinetics of [3H]cGMP binding to the two rapidly exchanging and two slowly exchanging sites of dimeric cGMP-dependent protein kinase from bovine lung were studied. As observed by McCune and Gill, unlabeled cGMP retarded the dissociation of [3H]cGMP bound to the slow site. This effect was due to interaction of unlabeled cGMP with the rapid rather than the slow site. First, the potencies of unlabeled cGMP and a number of cGMP analogs correlated nearly perfectly with their affinities for the rapid site. Second, the rate of dissociation in the absence of unlabeled ligand was independent of the degree of saturation of the slow sites. Third, unlabeled ligand inhibited the rate of dissociation more (about 10-fold) than theoretically predicted (maximum 2-fold) from interaction between two similar sites in one macromolecule. A favorable free energy coupling appeared to exist between the rapid and slow sites but not between the slow sites. cGMP associated faster to the slow site than the rapid site. Mg/ATP decreased the rate of association to either site by 50% and increased about ten-fold the rate of dissociation from the slow site. The dissociation of cGMP from the slow site could be described by a single activation energy (Ea = 71 kJ X mol-1) for the whole temperature range (0-37 degrees C) tested. These data indicated that the cyclic nucleotide-binding sites of the cGMP-kinase are kinetically more homologous to those in the cAMP-dependent protein kinases than previously recognized

  7. Activated G-protein releases cGMP from high affinity binding sites on PDE from toad rod outer segments (ROS)

    cGMP binding proteins in toad ROS were identified by direct photoaffinity labeling (PAL) with 32P-cGMP and quantified by retention of complexes on nitrocellulose filters. By PAL, high affinity sites were present on the α and β subunits of the cGMP-specific phosphodiesterase (PDE) which have MW/sub app/ of 94 and 90 kDa. A doublet was deduced from its photolabeling properties to represent PDE/sub γ/ photocrosslinked with PDE/sub α/ or PDE/sub β/, respectively. cGMP prebound to these high affinity sites was released by light-activated G-protein or its α subunit complexed with GTPγS; this inhibition of cGMP binding to PDE did not result from decreased cGMP availability due to enhanced hydrolysis. A low affinity cGMP binding component identified by PAL is tightly associated with ROS membranes. Apparent ATP/light-dependent stimulation of cGMP binding was shown to result from light activated cGMP hydrolysis in conjunction with ATP-promoted conversion of GMP to GDP/GTP and increased GDP/GTP binding. These findings coincide with a model for light-related regulation of cGMP binding and metabolism predicted from intact and cellfree kinetic measurements: in the dark state the cGMP hydrolic rate is constrained by the availability of cGMP because of its binding to high affinity sites on PDE. Light activated G-protein releases cGMP from these sites and allows for its redistribution to lower affinity sites represented by PDE catalytic site(s) and possible cGMP-dependent membrane cation channels

  8. 48th Annual Convention of Computer Society of India

    Avadhani, P; Udgata, Siba; Lakshminarayana, Sadasivuni; ICT and Critical Infrastructure

    2014-01-01

      This volume contains 85 papers presented at CSI 2013: 48th Annual Convention of Computer Society of India with the theme “ICT and Critical Infrastructure”. The convention was held during 13th –15th December 2013 at Hotel Novotel Varun Beach, Visakhapatnam and hosted by Computer Society of India, Vishakhapatnam Chapter in association with Vishakhapatnam Steel Plant, the flagship company of RINL, India. This volume contains papers mainly focused on Data Mining, Data Engineering and Image Processing, Software Engineering and Bio-Informatics, Network Security, Digital Forensics and Cyber Crime, Internet and Multimedia Applications and E-Governance Applications.

  9. From bedside to bench--meeting report of the 7th International Conference on cGMP "cGMP: generators, effectors and therapeutic implications" in Trier, Germany, from June 19th to 21st 2015.

    Friebe, Andreas; Sandner, Peter; Seifert, Roland

    2015-12-01

    During the past decade, our knowledge on the physiology, pathophysiology, basic pharmacology, and clinical pharmacology of the second messenger (cGMP) has increased tremendously. It is now well-established that cGMP, generated by soluble and particulate guanylate cyclases, is highly compartmentalized in cells and regulates numerous body functions. New cGMP-regulated physiological functions include meiosis and temperature perception. cGMP is involved in the genesis of numerous pathologies including cardiovascular, pulmonary, endocrine, metabolic, neuropsychiatric, eye, and tumor diseases. Several new clinical uses of stimulators and activators of soluble guanylate cyclase and of phosphodiesterase inhibitors such as heart failure, kidney failure, cognitive disorders, obesity bronchial asthma, and osteoporosis are emerging. The combination of neprilysin inhibitors-enhancing stimulation of the particulate guanylate cyclase pathway by preventing natriuretic peptide degradation-with angiotensin AT1 receptor antagonists constitutes a novel promising strategy for heart failure treatment. The role of oxidative stress in cGMP signaling, application of cGMP sensors, and gene therapy for degenerative eye diseases are emerging topics. It is anticipated that cGMP research will further prosper over the next years and reach out into more and more basic and clinical disciplines. PMID:26486926

  10. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    Leitman, D.C.

    1988-01-01

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP.

  11. Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

    Kandasamy, S. B.; Williaes, B. A.

    1983-01-01

    It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

  12. Atrial natriuretic peptide receptor heterogeneity and effects on cyclic GMP accumulation

    The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using 125I-ANP8-33. Specific 125I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a molecular size of 66,000 daltons under reducing conditions. The identification of cultured cell types in which hormones (ANP and oxytocin) regulate guanylate cyclase activity and increase cyclic GMP synthesis will provide valuable systems to determine the mechanisms of hormone-receptor coupling to guanylate cyclase and the cellular processes regulated by cyclic GMP

  13. Connection between the elastic GEp/GMp and P to Delta form factors

    Stoler, P

    2003-01-01

    It is suggested that the falloff in Qsq of the P to Delta magnetic form factor GM* is related to the recently observed falloff of the elastic electric form factor GEp/GMp. Calculation is carried out in the framework of a two-body GPD mechanism.

  14. MECHANISM FOR INTRODUCTION OF GMP INTERNATIONAL STANDARDS INTO THE PHARMACEUTICAL SECTOR OF UKRAINIAN ECONOMY

    Ovcharenko, T.; Yermolayeva, V.

    2009-01-01

    In the article the modern consisting and problems of the introduce international standards of GMP in pharmaceutical sector of the national economy is analyzed. The article suggests the ways for improving the international standards system that positively influences on the medicine quality of provision in Ukraine.

  15. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S; Thomsen, L L; Birk, S; Olesen, J.

    2004-01-01

    Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determin...

  16. A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function

    Aileen Balkow

    2015-08-01

    Conclusions: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes.

  17. FOREWORD: 13th International Workshop on Plasma-Facing Materials and Components for Fusion Applications/1st International Conference on Fusion Energy Materials Science 13th International Workshop on Plasma-Facing Materials and Components for Fusion Applications/1st International Conference on Fusion Energy Materials Science

    Jacob, Wolfgang; Linsmeier, Christian; Rubel, Marek

    2011-12-01

    The 13th International Workshop on Plasma-Facing Materials and Components (PFMC-13) jointly organized with the 1st International Conference on Fusion Energy Materials Science (FEMaS-1) was held in Rosenheim (Germany) on 9-13 May 2011. PFMC-13 is a successor of the International Workshop on Carbon Materials for Fusion Applications series. Between 1985 and 2003 ten 'Carbon Workshops' were organized in Jülich, Stockholm and Hohenkammer. Then it was time for a change and redefinition of the scope of the symposium to reflect the new requirements of ITER and the ongoing evolution in the field. Under the new name (PFMC-11), the workshop was first organized in 2006 in Greifswald, Germany and PFMC-12 took place in Jülich in 2009. Initially starting in 1985 with about 40 participants as a 1.5 day workshop, the event has continuously grown to about 220 participants at PFMC-12. Due to the joint organization with FEMaS-1, PFMC-13 set a new record with more than 280 participants. The European project Fusion Energy Materials Science, FEMaS, coordinated by the Max-Planck-Institut für Plasmaphysik (IPP), organizes and stimulates cooperative research activities which involve large-scale research facilities as well as other top-level materials characterization laboratories. Five different fields are addressed: benchmarking experiments for radiation damage modelling, the application of micro-mechanical characterization methods, synchrotron and neutron radiation-based techniques and advanced nanoscopic analysis based on transmission electron microscopy. All these fields need to be exploited further by the fusion materials community for timely materials solutions for a DEMO reactor. In order to integrate these materials research fields, FEMaS acted as a co-organizer for the 2011 workshop and successfully introduced a number of participants from research labs and universities into the PFMC community. Plasma-facing materials experience particularly hostile conditions as they are

  18. Pro-survival effects of 17β-estradiol on osteocytes are mediated by nitric oxide/cGMP via differential actions of cGMP-dependent protein kinases I and II.

    Marathe, Nisha; Rangaswami, Hema; Zhuang, Shunhui; Boss, Gerry R; Pilz, Renate B

    2012-01-01

    Estrogens promote bone health in part by increasing osteocyte survival, an effect that requires activation of the protein kinases Akt and ERK1/2, but the molecular mechanisms involved are only partly understood. Because estrogens increase nitric oxide (NO) synthesis and NO can have anti-apoptotic effects, we examined the role of NO/cGMP signaling in estrogen regulation of osteocyte survival. Etoposide-induced death of MLO-Y4 osteocyte-like cells, assessed by trypan blue staining, caspase-3 cleavage, and TUNEL assays, was completely prevented when cells were pre-treated with 17β-estradiol. This protective effect was mimicked when cells were pre-treated with a membrane-permeable cGMP analog and blocked by pharmacological inhibitors of NO synthase, soluble guanylate cyclase, or cGMP-dependent protein kinases (PKGs), supporting a requirement for NO/cGMP/PKG signaling downstream of 17β-estradiol. siRNA-mediated knockdown and viral reconstitution of individual PKG isoforms demonstrated that the anti-apoptotic effects of estradiol and cGMP were mediated by PKG Iα and PKG II. Akt and ERK1/2 activation by 17β-estradiol required PKG II, and cGMP mimicked the effects of estradiol on Akt and ERK, including induction of ERK nuclear translocation. cGMP induced BAD phosphorylation on several sites, and experiments with phosphorylation-deficient BAD mutants demonstrated that the anti-apoptotic effects of cGMP and 17β-estradiol required BAD phosphorylation on Ser(136) and Ser(155); these sites were targeted by Akt and PKG I, respectively, and regulate BAD interaction with Bcl-2. In conclusion, 17β-estradiol protects osteocytes against apoptosis by activating the NO/cGMP/PKG cascade; PKG II is required for estradiol-induced activation of ERK and Akt, and PKG Iα contributes to pro-survival signaling by directly phosphorylating BAD. PMID:22117068

  19. cGMP modulates stem cells differentiation to neurons in brain in vivo.

    Gómez-Pinedo, U; Rodrigo, R; Cauli, O; Herraiz, S; Garcia-Verdugo, J-M; Pellicer, B; Pellicer, A; Felipo, V

    2010-02-17

    During brain development neural stem cells may differentiate to neurons or to other cell types. The aim of this work was to assess the role of cGMP (cyclic GMP) in the modulation of differentiation of neural stem cells to neurons or non-neuronal cells. cGMP in brain of fetuses was reduced to 46% of controls by treating pregnant rats with nitroarginine-methylester (L-NAME) and was restored by co-treatment with sildenafil.Reducing cGMP during brain development leads to reduced differentiation of stem cells to neurons and increased differentiation to non-neuronal cells. The number of neurons in the prefrontal cortex originated from stem cells proliferating on gestational day 14 was 715+/-14/mm(2) in control rats and was reduced to 440+/-29/mm(2) (61% of control) in rats treated with L-NAME. In rats exposed to L-NAME plus sildenafil, differentiation to neurons was completely normalized, reaching 683+/-11 neurons/mm(2). In rats exposed to sildenafil alone the number of cells labelled with bromodeoxyuridine (BrdU) and NeuN was 841+/-16/mm(2). In prefrontal cortex of control rats 48% of the neural stem cells proliferating in gestational day 14 differentiate to neurons, but only 24% in rats exposed to L-NAME. This was corrected by sildenafil, 40% of cells differentiate to neurons. Similar results were obtained for neurons proliferating during all developmental period. Treatment with L-NAME did not reduce the total number of cells labelled with BrdU, further supporting that L-NAME reduces selectively the differentiation of stem cells to neurons. Similar results were obtained in hippocampus. Treatment with L-NAME reduced the differentiation of neural stem cells to neurons, although the effect was milder than in prefrontal cortex. These results support that cGMP modulates the fate of neural stem cells in brain in vivo and suggest that high cGMP levels promote its differentiation to neurons while reduced cGMP levels promote differentiation to non-neuronal cells. PMID:19958812

  20. Cyclic di-GMP is essential for the survival of the lyme disease spirochete in ticks.

    Ming He

    2011-06-01

    Full Text Available Cyclic dimeric GMP (c-di-GMP is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1, which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol. To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host.

  1. 13th Techtextil Closes with Record Figures

    2009-01-01

    @@ The technical textile and nonwovens sector came in droves to its leading international trade fair, with numbers never before seen. "Precisely because these are times of economic uncertainty, companies have been setting themselves new targets with innovative products and areas of application -and have in part already managed to achieve them at Techtextil. Some eight percent more exhibitors and two percent more trade visitors represent a double plus for Techtextil - a fantastic outcome," summarizes Detlef Braun, Member of the Board of Management of Messe Frankfurt, looking back over the days of the trade fair.

  2. 13th Radiochemical Conference. Booklet of Abstracts

    The Conference included the following sessions: (i) Opening plenary presentations (6 contributions); (ii) Chemistry of natural radionuclides, discovery of radium and polonium (6 verbal presentations + 5 poster presentations); (iii) Radionuclides in the environment, radioecology (29 + 48); (iv) Activation analysis and other radioanalytical methods (36 + 49); (v) Ionizing radiation in science and technology (12 + 12); (vi) Chemistry of actinide and trans-actinide elements (11 + 14); (vii) Separation methods, speciation (18 + 41); (viii) Production and application of radionuclides (14 + 29); and (ix) Radiochemical problems in nuclear waste management (12 + 22). The majority of verbal presentations has been input to INIS, mostly in the form of the full authors' abstracts. (P.A.)

  3. PREFACE: 13th International Conference on Electrostatics

    Taylor, D. Martin

    2011-06-01

    Electrostatics 2011 was held in the city of Bangor which is located in North West Wales in an area of outstanding natural beauty close to the Snowdonia mountain range and bordering the Irish Sea. The history of the area goes back into the mists of times, but a continuous technological thread can be traced from the stone- and bronze-age craftsmen, who inhabited the area several thousand years ago, via the civil engineering and fortifications of the Romans and Edward I of England, through Marconi's long-wave trans-Atlantic transmitter near Caernarfon to the conference host. The School of Electronic Engineering at Bangor University has contributed much to the discipline of Electrostatics not only in teaching and research but also in supporting industry. It was a great pleasure for me, therefore, to have the pleasure of welcoming the world's experts in Electrostatics to Bangor in April 2011. In my preface to the Proceedings of Electrostatics 1999, I reported that almost 90 papers were presented. Interestingly, a similar number were presented in 2011 testifying to the importance and endurance of the subject. The all-embracing nature of electrostatics is captured in the pictorial depiction used for the conference logo: a hand-held plasma ball with its close link to gaseous discharges and the superimposed Antarctic aurora highlighting the featured conference themes of atmospheric, planetary and environmental electrostatics. Leading these themes were three invited contributions, the first by Giles Harrison who delivered the Bill Bright Memorial Lecture 'Fair weather atmospheric electricity', Carlos Calle on 'The electrostatic environments of Mars and the Moon' and Istvan Berta on 'Lightning protection - challenges, solutions and questionable steps in the 21st century'. Leading other key sessions were invited papers by Atsushi Ohsawa on 'Statistical analysis of fires and explosions attributed to static electricity over the last 50 years in Japanese industry' and Antonio Ramos on 'Electrohydrodynamic pumping in microsystems'. Of the papers submitted for publication 69 passed through the thorough review process and I take this opportunity to warmly thank the reviewers for their constructive criticism and rapid turnaround which has allowed the Proceedings to be delivered to the publisher on time. It is a pleasure also to thank members of the International Advisory Panel, and the Organizing and Programme Committees for their guidance and suggestions and especially Claire Garland and her team at the Institute of Physics for their support, all of which ensured a successful and enjoyable conference. Special thanks are due to Jeremy Smallwood for organising the pre-conference workshop, to Tom Jones, Martin Glor and Dave Swenson for their highly informative and educational contributions at the workshop, to CST for organising the simulation workshop, and to CST and JCI Chilworth for their much appreciated sponsorship of the conference. I am sure you will enjoy reading this record of Electrostatics 2011, covering as it does the wide range of subjects upon which static electricity impinges. Especially important is the development of electrostatic-based methods for reducing atmospheric pollution. In this context it is interesting to see how Masuda's work on the surface-discharge-based Boxer charger, first reported over 30 years ago, has now developed into dielectric barrier discharge (DBD) systems for the removal of noxious molecules from industrial and vehicle exhaust gases. Thanks to our hard working conference chairman, Paul Holdstock, the conference retained its now well-established reputation for providing a friendly, sociable atmosphere for discussing the newest developments in this important scientific area. Finally, my sincere thanks go to all the presenters and to all those who attended and contributed to another successful conference. Professor D. Martin TaylorProceedings EditorBangor, May 2011

  4. Involvement of cyclic GMP in phytochrome-controlled flowering of Pharbitis nil.

    Szmidt-Jaworska, Adriana; Jaworski, Krzysztof; Kopcewicz, Jan

    2008-05-26

    Light is one of the most important environmental factors influencing the induction of flowering in plants. Light is absorbed by specific photoreceptors--the phytochromes and cryptochromes system--which fulfil a sensory and a regulatory function in the process. The absorption of light by phytochromes initiates a cascade of related biochemical events in responsive cells, and subsequently changes plant growth and development. Induction of flowering is controlled by several paths. One is triggered by the guanosine-3':5'-cyclic monophosphate (cGMP) level. Thus, the aim of our study was to investigate the role of cGMP in phytochrome-controlled flowering. It is best to conduct such research on short-day plants because the photoperiodic reactions of only these plants are totally unequivocal. The most commonly used plant is the model short-day plant Pharbitis nil. The seedlings of P. nil were cultivated under special photoperiodic conditions: 72-h-long darkness, 24-h-long white light with low intensity and 24-h-long inductive night. Such light conditions cause a degradation of the light-labile phytochrome. Far red (FR) treatment before night causes inactivation of the remaining light-stable phytochrome. During the 24-h-long inductive darkness period, the total amount of cGMP in cotyledons underwent fluctuations, with maxima at the 4th, 8th and 14th hours. When plants were treated with FR before the long night, fluctuations were not observed. A red light pulse given after FR treatment could reverse the effect induced by FR, and the oscillation in the cGMP level was observed again. Because the intracellular level of cGMP is controlled by the opposite action of guanylyl cyclases (GCs) and phosphodiesterases (PDEs), we first tested whether accumulation of the nucleotide in P. nil tissue may be changed after treatment with a GC stimulator or PDE inhibitor. Accumulation of the nucleotide in P. nil cotyledons treated with a stimulator of cGMP synthesis (sodium nitroprusside) was

  5. "十三五"时期创新开放发展模式的思考与建议%Thoughts and Suggestions of Innovative Opening Development Mode During the 13th Five-year Plan

    周军伟

    2015-01-01

    本研究以郑州市为例,从分析郑州市对外开放现状、存在问题和面临形势着手,重点研究"一带一路"对未来对外开放新格局的影响,推动更高水平、更宽领域、更大规模对外开放,深度融入国家"一带一路"战略;如何以开放促改革、促发展,加快政府管理和监管体制创新,营造国际化、法制化的营商环境,更好地适应构建开放型经济新体制新要求,使投资更加便利、贸易更加自由、经济更加开放.因此,从创新定位理念、创新发展路径、创新体制机制等方面,提出郑州市"十三五"期间创新开放发展模式、加快对外开放工作的政策措施建议,为当前正在编制"十三五"规划的相关同类地市提供决策参考.%The research takes Zhengzhou as an example, analyzes its opening status, the existing problems and the present situation. It focuses on the impacts of"One belt, one road"on the new opening pattern in the fu?ture, which may promote the reform and opening at higher levels, wider areas, and larger scales, deeply integrate into the country's"One belt, one road"strategy. How to promote reform and development through opening, ac?celerate innovation of the management and the supervision system of the local government, and create an interna?tional and legal business environment, better adapt to the new requirements of build a new opening economic system to make the investments more convenient, the trades much free, and the economy more open. Therefore, from the aspects of the innovation-oriented concepts, paths and mechanisms, the essay proposes the mode of in?novative and opening development during the 13th five-year plan and puts forward the suggestions of speeding upopening policy measures, providing a reference to other same-level cities when they make policies of the 13th five-year plan.

  6. Construction Conceptions and Key Technologies about Water Resources Informatization during 13th Five-Year%全国水利信息化“十三五”建设构想与关键技术

    李臣明; 曾焱; 王慧斌; 张丽丽

    2015-01-01

    13th Five-Year is one important stage to push forward water resources modernization process and promote water safety guarantee capability. Based on major changes of informatization strategy and water control policy of China, and requirement about water resources informatization which is put forward by water deepening reform, it is necessary to anew comb and plan technology system and strategy of informatization construction combining with developmental feature of latest information technology. This paper analyzes the relationship between information developing process and capability of information ability raise, and obtains the meaning of water resources informatization construction in the current emergency of the improvement of the information capability. It also states 13th Five-Year water resources informatization construction and technical ideas whose central content is informatization resource management and service, and gives some suggestions on how to construct and implement about the important parts in detail.%“十三五”是推进水利现代化进程、提升水安全保障能力的重要时期,根据国家信息化战略和治水方略的重大调整,以及水利深化改革对水利信息化提出的要求,有必要结合最新信息技术发展特点,重新梳理和规划信息化建设中的技术体系和策略。分析信息化发展过程与信息能力提升之间的关系,明确当前水利信息化正处于以提升信息能力为核心的水利信息化建设内涵,基于信息能力视角,论述以信息化资源管理与服务为中心内容的“十三五”水利信息化建设体系和技术构想,并对建设重点和实施的关键技术进行阐述说明。

  7. Changes of platelet GMP-140 in diabetic nephropathy and its multi-factor regression analysis

    The relation of platelet GMP-140 and its related factors with diabetic nephropathy was studied. 144 patients of diabetic mellitus without nephropathy (group without DN, mean suffering duration of 25.5 +- 18.6 months); 80 with diabetic nephropathy (group DN, mean suffering duration of 58.7 +- 31.6 months) and 50 normal controls were chosen in the research. Platelet GMP-140, plasma α1-MG, β2-MG, and 24 hour urine albumin (ALB), IgG, α1-MG, β2-MG were detected by RIA, while HBA1C via chromatographic separation and FBG, PBG, Ch, TG, HDL, FG via biochemical methods. All the data had been processed with software on computer with t-test and linear regression, and multi-factor analysis were done also. The levels of platelet GMP-140, FG, DBP, TG, HBA1C and PBG in group DN were significantly higher than those of group without DN and normal control (P 0.05), while they were higher than those of normal controls. Multi-factor analysis of platelet GMP-140 with TG, DBP and HBA1C were performed in 80 patients with DN (P 1C are the independent factors enhancing the activation of platelets. The disturbance of lipid metabolism in type II diabetic mellitus may also enhance the activation of platelets. Elevation of blood pressure may accelerate the initiation and deterioration of DN in which change of platelet GMP-140 is an independent factor. Elevation of HBA1C and blood glucose are related closely to the diabetic nephropathy

  8. Structural Analysis of the GGDEF-EAL Domain-Containing c-di-GMP Receptor FimX

    Navarro, M.; De, N; Bae, N; Wang, Q; Sondermann, H

    2009-01-01

    Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data and crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.

  9. Inhibitory effect of dibutyryl cyclic GMP on potassium-stimulated 45Ca uptake by synaptosomes from rat brain

    The effects of dibutyryl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by the P2 fraction of Gray and Whittaker were investigated with the following results. (1)db-cGMP inhibited initial rate of potassium-stimulated 45Ca-uptake in a dose-dependent manner in 0.1 mM Ca0 medium, but had no effect on the uptake in low K+ medium. In 0.1 mM Ca0 medium, the concentration of db-cGMP causing 50% inhibition was about 3 mM. db-cAMP (5mM) had no effect on the uptake. (2) db-cGMP inhibited potassium-stimulated 45Ca uptake in 1 mM Ca0 medium, though less than in 0.1 mM Ca0 medium. (3) db-cGMP inhibited potassium-stimulated 45Ca uptake by synaptosomes (pinched-off nerve terminals) more than the uptakes by other subfractions of P2 fraction. It is suggested from the results that cGMP inhibits the Ca influx resulting from depolarization of the nerve endings in situ. (Auth.)

  10. The participation of elevated levels of cyclic GMP in the recovery from radiation-induced mitotic delay

    The levels of cyclic AMP and cyclic GMP have been measured in Physarum plasmodia before and after treatment with gamma-radiation, 2 mM caffeine, or combinations of the two agents compared to the length of the radiation-induced mitotic delay. Caffeine alone produces a rapid transient elevation of cyclic AMP and a slower delayed elevation of cyclic GMP. Irradiation elicits an immediate transient increase in cyclic AMP and a later cyclic GMP increase which accompanies or precedes the delayed mitosis. A composite pattern is produced by combinations of radiation and caffeine, a distinctive feature of which is an elevated level of cyclic GMP near the time of the radiation-delayed and caffeine-promoted mitosis. With pretreatment by caffeine, the least radiation-induced mitotic delay occurs when plasmodia are irradiated during the caffeine-elicited increase in cyclic GMP. The plasmodium becomes refractory to the reduction of mitotic delay by caffeine at approximately the time it becomes refractory to the further elevation of cyclic GMP by caffeine. The data support a role for cyclic AMP in the onset of and for cyclic GMP in the recovery from mitotic delay induced by ionizing radiation. (author)

  11. Intestinal GPS: bile and bicarbonate control cyclic di-GMP to provide Vibrio cholerae spatial cues within the small intestine.

    Koestler, Benjamin J; Waters, Christopher M

    2014-01-01

    The second messenger cyclic di-GMP (c-di-GMP) regulates numerous phenotypes in response to environmental stimuli to enable bacteria to transition between different lifestyles. Here we discuss our recent findings that the human pathogen Vibrio cholerae recognizes 2 host-specific signals, bile and bicarbonate, to regulate intracellular c-di-GMP. We have demonstrated that bile acids increase intracellular c-di-GMP to promote biofilm formation. We have also shown that this bile-mediated increase of intracellular c-di-GMP is negated by bicarbonate, and that this interaction is dependent on pH, suggesting that V. cholerae uses these 2 environmental cues to sense and adapt to its relative location in the small intestine. Increased intracellular c-di-GMP by bile is attributed to increased c-di-GMP synthesis by 3 diguanylate cyclases (DGCs) and decreased expression of one phosphodiesterase (PDE) in the presence of bile. The molecular mechanisms by which bile controls the activity of the 3 DGCs and the regulators of bile-mediated transcriptional repression of the PDE are not yet known. Moreover, the impact of varying concentrations of bile and bicarbonate at different locations within the small intestine and the response of V. cholerae to these cues remains unclear. The native microbiome and pharmaceuticals, such as omeprazole, can impact bile and pH within the small intestine, suggesting these are potential unappreciated factors that may alter V. cholerae pathogenesis. PMID:25621620

  12. A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.

    Skotnicka, Dorota; Smaldone, Gregory T; Petters, Tobias; Trampari, Eleftheria; Liang, Jennifer; Kaever, Volkhard; Malone, Jacob G; Singer, Mitchell; Søgaard-Andersen, Lotte

    2016-05-01

    Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-di-GMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be-at least partially-functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus. PMID:27214040

  13. Characterization of particulate cyclic nucleotide phosphodiesterases from bovine brain: Purification of a distinct cGMP-stimulated isoenzyme

    In the absence of detergent, ∼80-85% of the total cGMP-stimulated phosphodiesterase (PDE) activity in bovine brain was associated with washed particulate fractions; ∼85-90% of the calmodulin-sensitive PDE was soluble. Particulate cGMP-stimulated PDE was higher in cerebral cortical gray matter than in other regions. Homogenization of the brain particulate fraction in 1% Lubrol increased cGMP-stimulated activity ∼100% and calmodulin-stimulated ∼400-500%. Although 1% Lubrol readily solubilized these PDE activities, ∼75% of the cAMP PDE activity (0.5 μM [3H]cAMP) that was not affected by cGMP was not solubilized. This cAMP PDE activity was very sensitive to inhibition by Rolipram but not cilostamide. Thus, three different PDE types, i.e., cGMP stimulated, calmodulin sensitive, and Rolipram inhibited, are associated in different ways with crude bovine brain particulate fractions. The brain enzyme exhibited a slightly greater subunit Mr than did soluble forms from calf liver or bovine brain, as evidenced by protein staining or immunoblotting after polyacrylamide gel electrophoresis under denaturing conditions. Incubation of brain particulate and liver soluble cGMP-stimulated PDEs with V8 protease produced several peptides of similar size, as well as at least two distinct fragments of ∼27 kDa from the brain and ∼23 kDa from the liver enzyme. After photolabeling in the presence of [32P]cGMP and digestion with V8 protease, [32P]cGMP in each PDE was predominantly recovered with a peptide of ∼14 kDa. All of these observations are consistent with the existence of at least two discrete forms (isoenzymes) of cGMP-stimulated PDE

  14. PDE5 is converted to an activated state upon cGMP binding to the GAF A domain

    Rybalkin, Sergei D.; Rybalkina, Irina G.; Shimizu-Albergine, Masami; Tang, Xiao-Bo; Beavo, Joseph A.

    2003-01-01

    cGMP-specific, cGMP-binding phosphodiesterase (PDE5) regulates such physiological processes as smooth muscle relaxation and neuronal survival. PDE5 contains two N-terminal domains (GAF A and GAF B), but the functional roles of these domains have not been determined. Here we show that recombinant PDE5 is activated directly upon cGMP binding to the GAF A domain, and this effect does not require PDE5 phosphorylation. PDE5 exhibited time- and concentration-dependent reversible activation in respo...

  15. 13th February 2012 - German CEO Barmenia Insurance Group and Chair of the Hochschulrat Board of Governors of the Bergische Universitaet Wuppertal J. Beutelmann visiting ATLAS experimental area and signing the guest book with CERN Director-General R. Heuer and Advise R. Voss.

    Maximilien Brice

    2012-01-01

    13th February 2012 - German CEO Barmenia Insurance Group and Chair of the Hochschulrat Board of Governors of the Bergische Universitaet Wuppertal J. Beutelmann visiting ATLAS experimental area and signing the guest book with CERN Director-General R. Heuer and Advise R. Voss.

  16. GMP compliant radiosynthesis of11C and18F-labeled PET radiopharmaceuticals with a modular disposable cassette system

    Hessels-Scheper, J.G.; Maarsingh, P.; Kwizera, C.; Zijlma, R.; Maas, B.; De Vries, A.M.T.; Antunes, I.F.; Lub-de Hooge, M.N.; Boersma, H.H.; Dierckx, R.A.J.O.; De Vries, E.F.J.; Luurtsema, G.; Elsinga, P.H.

    2014-01-01

    Background Many nuclear medicine departments have an extensive radiopharmaceutical portfolio. Consequently, these multiple PET radiopharmaceuticals have to be produced with the same synthesis module. An important consideration in GMP-compliant PET production is to avoid potential cross-contamination

  17. Regulation of hippocampal cGMP levels as a candidate to treat cognitive deficits in Huntington's disease.

    Ana Saavedra

    Full Text Available Huntington's disease (HD patients and mouse models show learning and memory impairment associated with hippocampal dysfunction. The neuronal nitric oxide synthase/3',5'-cyclic guanosine monophosphate (nNOS/cGMP pathway is implicated in synaptic plasticity, and in learning and memory processes. Here, we examined the nNOS/cGMP pathway in the hippocampus of HD mice to determine whether it can be a good therapeutic target for cognitive improvement in HD. We analyzed hippocampal nNOS and phosphodiesterase (PDE 5 and 9 levels in R6/1 mice, and cGMP levels in the hippocampus of R6/1, R6/2 and Hdh(Q7/Q111 mice, and of HD patients. We also investigated whether sildenafil, a PDE5 inhibitor, could improve cognitive deficits in R6/1 mice. We found that hippocampal cGMP levels were 3-fold lower in 12-week-old R6/1 mice, when they show deficits in object recognition memory and in passive avoidance learning. Consistent with hippocampal cGMP levels, nNOS levels were down-regulated, while there were no changes in the levels of PDE5 and PDE9 in R6/1 mice. A single intraperitoneal injection of sildenafil (3 mg/Kg immediately after training increased cGMP levels, and improved memory in R6/1 mice, as assessed by using the novel object recognition and the passive avoidance test. Importantly, cGMP levels were also reduced in R6/2 mouse and human HD hippocampus. Therefore, the regulation of hippocampal cGMP levels can be a suitable treatment for cognitive impairment in HD.

  18. Identification of a cyclic-di-GMP-modulating response regulator that impacts biofilm formation in a model sulfate reducing bacterium

    AindrilaMukhopadhyay

    2014-07-01

    Full Text Available We surveyed the eight putative cyclic-di-GMP-modulating response regulators (RRs in Desulfovibrio vulgaris Hildenborough that are predicted to function via two-component signaling. Using purified proteins, we examined cyclic-di-GMP production or turnover in vitro of all eight proteins. The two RRs containing only GGDEF domains (DVU2067, DVU0636 demonstrated cyclic-di-GMP production activity in vitro. Of the remaining proteins, three RRs with HD-GYP domains (DVU0722, DVUA0086 and DVU2933 were confirmed to be Mn2+ dependent phosphodiesterases in vitro and converted cyclic-di-GMP to its linear form, pGpG. DVU0408, containing both cyclic-di-GMP production (GGDEF and degradation domains (EAL, showed cyclic-di-GMP turnover activity in vitro also with production of pGpG. No cyclic-di-GMP related activity could be assigned to the RR DVU0330, containing a metal-dependent phosphohydrolase HD-OD domain, or to the HD-GYP domain RR, DVU1181. Studies included examining the impact of overexpressed cyclic-di-GMP-modulating RRs in the heterologous host E. coli and led to the identification of one RR, DVU0636, with increased cellulose production. Evaluation of a transposon mutant in DVU0636 indicated that the strain was impaired in biofilm formation and demonstrated an altered carbohydrate:protein ratio relative to the D. vulgaris wild type biofilms. However, grown in liquid lactate/sulfate medium, the DVU0636 transposon mutant showed no growth impairment relative to the wild-type strain. Among the eight candidates, only the transposon disruption mutant in the DVU2067 RR presented a growth defect in liquid culture. Our results indicate that, of the two diguanylate cyclases that function as part of two-component signaling, DVU0636 plays an important role in biofilm formation while the function of DVU2067 has pertinence in planktonic growth.

  19. Clinical Grade Treg: GMP Isolation, Improvement of Purity by CD127pos Depletion, Treg Expansion, and Treg Cryopreservation

    Peters, Jorieke H; Preijers, Frank W.; Rob Woestenenk; Hilbrands, Luuk B; Koenen, Hans J.P.M.; Irma Joosten

    2008-01-01

    BACKGROUND: Treg based immunotherapy is of great interest to facilitate tolerance in autoimmunity and transplantation. For clinical trials, it is essential to have a clinical grade Treg isolation protocol in accordance with Good Manufacturing Practice (GMP) guidelines. To obtain sufficient Treg for immunotherapy, subsequent ex vivo expansion might be needed. METHODOLOGY/PRINCIPAL FINDINGS: Treg were isolated from leukapheresis products by CliniMACS based GMP isolation strategies, using anti-C...

  20. Genetic locus (stmF) associated with cyclic GMP phosphodiesterase activity in Dictyostelium discoideum maps in linkage group II.

    Coukell, M. B.; Cameron, A M

    1985-01-01

    Previous attempts to map the stmF locus in Dictyostelium discoideum, by using only clone morphology as a marker, have led to equivocal results. Since strains carrying mutations at the stmF locus possess very low cyclic GMP phosphodiesterase activity, we have remapped this locus using both morphological and biochemical markers. Our results indicate that mutations producing a stable "streamer" phenotype and reduced cyclic GMP phosphodiesterase activity are located in linkage group II, probably ...

  1. Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I

    Frantz, Stefan; Klaiber, Michael; Baba, Hideo A.; Oberwinkler, Heinz; Völker, Katharina; Gaßner, Birgit; Bayer, Barbara; Abeßer, Marco; Schuh, Kai; Feil, Robert; Hofmann, Franz; Kuhn, Michaela

    2016-01-01

    Aims: Cardiac hypertrophy is a common and often lethal complication of arterial hypertension. Elevation of myocyte cyclic GMP levels by local actions of endogenous atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) or by pharmacological inhibition of phosphodiesterase-5 was shown to counter-regulate pathological hypertrophy. It was suggested that cGMP-dependent protein kinase I (cGKI) mediates this protective effect, although the role in vivo is under debate. Here, we inves...

  2. Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit.

    Lem, J.; Flannery, J. G.; Li, T; Applebury, M L; Farber, D B; Simon, M. I.

    1992-01-01

    The beta subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE beta subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photorecept...

  3. Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase ß subunit

    Lem, Janis; Flannery, John G.; Li, Tiansen; Applebury, Meredithe L.; Farber, Debora B.; Simon, Melvin I.

    1992-01-01

    The ß subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE ß subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photoreceptors in...

  4. Genetic reductionist approach for dissecting individual roles of GGDEF proteins within the c-di-GMP signaling network in Salmonella

    Solano, Cristina; García, Begoña; Latasa, Cristina; Toledo-Arana, Alejandro; Zorraquino, Violeta; Valle, Jaione; Casals, Joan; Pedroso, Enrique; Lasa, Iñigo

    2009-01-01

    Bacteria have developed an exclusive signal transduction system involving multiple diguanylate cyclase and phosphodiesterase domain-containing proteins (GGDEF and EAL/HD-GYP, respectively) that modulate the levels of the same diffusible molecule, 3′-5′-cyclic diguanylic acid (c-di-GMP), to transmit signals and obtain specific cellular responses. Current knowledge about c-di-GMP signaling has been inferred mainly from the analysis of recombinant bacteria that either lack or overproduce individ...

  5. Tetrameric assembly of hGBP1 is crucial for both stimulated GMP formation and antiviral activity.

    Pandita, Esha; Rajan, Sudeepa; Rahman, Safikur; Mullick, Ranajoy; Das, Saumitra; Sau, Apurba Kumar

    2016-06-15

    Interferon-γ inducible human guanylate binding protein-1 (hGBP1) shows a unique characteristic that hydrolyses GTP to a mixture of GDP and GMP through successive cleavages, with GMP being the major product. Like other large GTPases, hGBP1 undergoes oligomerization upon substrate hydrolysis, which is essential for the stimulation of activity. It also exhibits antiviral activity against many viruses including hepatitis C. However, which oligomeric form is responsible for the stimulated activity leading to enhanced GMP formation and its influence on antiviral activity, are not properly understood. Using mutant and truncated proteins, our data indicate that transition-state-induced tetramerization is associated with higher rate of GMP formation. This is supported by chimaeras that are defective in both tetramerization and enhanced GMP formation. Unlike wild-type protein, chimaeras did not show allosteric interactions, indicating that tetramerization and enhanced GMP formation are allosterically coupled. Hence, we propose that after the cleavage of the first phosphoanhydride bond GDP·Pi-bound protein dimers transiently associate to form a tetramer that acts as an allosteric switch for higher rate of GMP formation. Biochemical and biophysical studies reveal that sequential conformational changes and interdomain communications regulate tetramer formation via dimer. Our studies also show that overexpression of the mutants, defective in tetramer formation in Rep2a cells do not inhibit proliferation of hepatitis C virus, indicating critical role of a tetramer in the antiviral activity. Thus, the present study not only highlights the importance of hGBP1 tetramer in stimulated GMP formation, but also demonstrates its role in the antiviral activity against hepatitis C virus. PMID:27071416

  6. Endothelin and a Ca2+ ionophore raise cyclic GMP levels in a neuronal cell line via formation of nitric oxide.

    Reiser, G.

    1990-01-01

    1. The vasoconstrictor peptide endothelin-1 caused a fast, transient rise in guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels in a neuronal cell line (mouse neuroblastoma x rat glioma hybrid cells 108CC15). The mechanism of activation of guanylate cyclase by endothelin-1 was investigated. The endothelin-1-induced rise depended on the release of internal Ca2+. 2. The stimulation of cyclic GMP synthesis induced by endothelin-1 was suppressed after preincubating the cells in medium conta...

  7. Improvements in the automated radioimmunoassay for cAMP or cGMP

    The work others in developing antibodies and the original radioimmunoassay for cyclic nucleotides provides the basis for these sensitive assays. The acetylation radioimmunoassay for cyclic nucleotides has enabled the measurement of cyclic AMP and cyclic GMP in very small biological samples. This is because accurate determinations can be made in samples containing less than 1 fmol of cyclic AMP or cyclic GMP. The Gamma-Flo automated radioimmunoassay system has been adapted to these assays such that cyclic nucleotides can be automatically measured at a rate of about 60 samples/hr. The Gamma-Flo instrument provides high-precision assays and eliminates human intervention in all steps of the radioimmunoassay. The automated assay has been in continuous operation in our laboratory over the last 10 years and this chapter summarizes the methodology and delineates improvements which have occurred over that time frame. Details for the preparation of the radioligands apply also to the manual acetylated radioimmunoassay for cyclic nucleotides

  8. Electrocatalytic activity of oxidation products of guanine and 5'-GMP towards the oxidation of NADH

    We have studied the potential electrocatalytic activity towards the oxidation of NADH of several oxidation products of guanine and its derivative guanosine-5'-monophosphate (5'-GMP) on pyrolytic graphite electrodes (PGE). The distribution of products generated strongly depends on the experimental conditions. Our investigations focused on the oxidation products that are adsorbed on the electrode surface, are redox active and, exhibited electrocatalytic activity toward the oxidation of NADH. These compounds were electrochemically and kinetically characterized in terms of dependence of the formal potential on pH and electron transfer rate constant (ks). The voltammetric and catalytic behavior of both guanine and 5'-GMP oxidation products was compared with that of other guanine derivatives we have previously studied. Some mechanistic aspects concerning the generation of the catalysts are also discussed

  9. Direct ionization effects of purine derivatives: ESR and ENDOR studies of 5'GMP

    In this study the free acid of 5' GMP was investigated (in the form of 5'GMP.3H/sub 2/O crystals). Irradiation and study of the molecular system below 10K gave evidence for at least three products in the ESR. Product I was also studied by ENDOR, and has been tentatively identified as the result of the anion protonated at 06. From the experimental data the spin distribution in product I is: 30% at C8; 12% at N1; 10% at N7. Product II was identified from its characteristic ESR as the result of hydrogen addition at C8. Product III was evident in the ESR but has not yet been identified

  10. Design and package of a 14CO2 field analyzer: the Global Monitor Platform (GMP)

    Marino, Bruno D. V.; Bright, Michelle; Gronniger, Glen

    2011-09-01

    Carbon Capture and Sequestration (CCS) is widely accepted as a means to reduce and eliminate the fossil fuel CO2 (ff- CO2) emissions from coal fired power plants. Success of CCS depends on near zero leakage rates over decadal time scales. Currently no commercial methods to determine leakage of ff-CO2 are available. The Global Monitor Platform (GMP) field analyzer provides high precision analysis of CO2 isotopes [12C (99%), 13C (Kyoto Protocol) and to characterize the nuclear fuel cycle. Planetary Emissions Management (PEM), working with the National Secure Manufacturing Center (NSMC), has the goal of designing, ruggedizing and packaging the GMP for field deployment. The system will conduct atmosphere monitoring then adapt to water and soil evaluations. Measuring 14CO2 in real time will provide quantitative concentration data for ff-CO2 in the atmosphere and CCS leakage detection. Initial results will be discussed along with design changes for improved detection sensitivity and manufacturability.