JSME: a free molecule editor in JavaScript.

PubMed

Bienfait, Bruno; Ertl, Peter

2013-01-01

A molecule editor, i.e. a program facilitating graphical input and interactive editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. Today, when a web browser has become the universal scientific user interface, a tool to edit molecules directly within the web browser is essential. One of the most popular tools for molecular structure input on the web is the JME applet. Since its release nearly 15 years ago, however the web environment has changed and Java applets are facing increasing implementation hurdles due to their maintenance and support requirements, as well as security issues. This prompted us to update the JME editor and port it to a modern Internet programming language - JavaScript. The actual molecule editing Java code of the JME editor was translated into JavaScript with help of the Google Web Toolkit compiler and a custom library that emulates a subset of the GUI features of the Java runtime environment. In this process, the editor was enhanced by additional functionalities including a substituent menu, copy/paste, drag and drop and undo/redo capabilities and an integrated help. In addition to desktop computers, the editor supports molecule editing on touch devices, including iPhone, iPad and Android phones and tablets. In analogy to JME the new editor is named JSME. This new molecule editor is compact, easy to use and easy to incorporate into web pages. A free molecule editor written in JavaScript was developed and is released under the terms of permissive BSD license. The editor is compatible with JME, has practically the same user interface as well as the web application programming interface. The JSME editor is available for download from the project web page http://peter-ertl.com/jsme/

Piracy in the Horn of Africa: A Comparative Study with Southeast Asia

DTIC Science & Technology

2009-12-01

Federal 2 Graham Gerard Ong-Webb, Piracy in Maritime Asia: Current Trends, ed. Peter Lehr (Routledge: New York, 2007), 55. 3 Catherine Zara ... Zara Raymond (Singapore: Institute of Defense and Strategic Studies, 2005), 61. 46 ICC International Maritime Bureau, Piracy and Armed Robbery against...Southeast Asia.” In The Best of Times, The Worst of Times: Maritime Security in the Asia-Pacific, edited by Joshua Ho and Catherine Zara Raymond, 61

Thermophysical Properties of Matter - the TPRC Data Series. Volume 14. Master Index - To Materials and Properties

DTIC Science & Technology

1979-01-01

Chloropentalfluoroothane - - - - - - - 11 140 1 - Chloropropane - 69 22 -- - - - Chlorosi lane - 6s 22 - - - - - - a-Chlorotoluens - 6s 22 - - - - - - -Chlorotofuene - 6s...Properties,’ Touloukian, 1 .S. and Ho, C. Y., 197 pp., 1979. To further expand this Data Series and to facilitate current research studies, this Master...Editor Volume 1 . Thermal Conductivity-Metallic Elements and Alloys Volume 2. Thermal Conductivity-Nonmetallic Solids Volume 3. Thermal Conductivity

"Can HIV be eradicated from an infected individual?" Piot, Ho and scientific community meet at 4th Retroviral Conference.

PubMed

Macinnis R

1997-01-01

More than 2300 medical and scientific professionals attended the 4th Conference on Retroviruses and Opportunistic Infection held in Washington, DC, during January 22-26, 1997, to discuss the latest information on treatment for HIV/AIDS and opportunistic infections. The keynote speakers were Dr. David Ho, a researcher at the Aaron Diamond AIDS Institute, and Dr. Peter Piot, Director of UNAIDS. Dr. Ho told the audience that reasons exist to be hopeful about prolonging the life of people with AIDS even though HIV has not yet been eliminated from any infected individual. He urged the media to carefully and accurately portray HIV/AIDS, and stressed that there is no cure for AIDS and that safer sex practices should be maintained in order to prevent the sexual transmission of HIV. In his address, Dr. Piot considered how HIV/AIDS treatment and care options translate to the reality of developing countries in which 90% of all HIV/AIDS cases reside. Recognizing researchers' accomplishments in developing treatment therapies against HIV/AIDS, Piot urged them to focus upon the development of preventive technology, including microbicides, vaccines, and a way to prevent mother-to-fetus HIV transmission. Dr. Piot also discussed a proposed UNAIDS plan to make advanced therapies against HIV/AIDS available in developing countries.

'Strategic approach' can reveal benefits.

PubMed

Baillie, Jonathan

2011-01-01

Speaking at last October's Healthcare Estates 2010 conference in Manchester, Peter Haggarty, assistant director, Health Facilities Scotland, outlined some of the key steps and priorities for large healthcare providers seeking to establish and implement an effective asset management strategy, focusing particularly on work ongoing in this area in the Scottish public health service. While any radical change to a large healthcare organisation's existing asset management practices could be "challenging", both for the organisation itself, and for its staff, with "sufficient planning, persistence, and support", such changes could, he told delegates, often result in "unanticipated benefits". HEJ editor Jonathan Baillie reports.

The RDF and Amphibious Warfare.

DTIC Science & Technology

1982-03-01

Retrieval oy Manfred Kocnen," 10 pp., Mcr 78 lPuolisnea 3s a Letter to the Editor, Journal of Documentation, vol. 31 , PP 226 No. 4, pages 298-301...ctlon rants,w 25 pp., 3cr 1979, ’C 4061 529 𔃿 ’~~~~~~-s’. Roa~ ., n a .e~nn mlzrani, marce i~., "The 38,i:,asslcaI -- efs70 71 . Soverai 5xiIeCTlI...a Vtaas," 71 Do-. an 1981, A2 V96.)5q 0nln 1. OIme0 2 -P 300 pp 313 Jondow. James and Schmildt. Peter, * wOn tha Estimation of Roberts, Stephen S

Adventures in public data

PubMed Central

2011-01-01

This article contains the slides and transcript of a talk given by Dan Zaharevitz at the "Visions of a Semantic Molecular Future" symposium held at the University of Cambridge Department of Chemistry on 2011-01-19. A recording of the talk is available on the University Computing Service's Streaming Media Service archive at http://sms.cam.ac.uk/media/1095515 (unfortunately the first part of the recording was corrupted, so the talk appears to begin at slide 6, 'At a critical time'). We believe that Dan's message comes over extremely well in the textual transcript and that it would be poorer for serious editing. In addition we have added some explanations and references of some of the concepts in the slides and text. (Charlotte Bolton; Peter Murray-Rust, University of Cambridge) Editorial preface The following paper is part of a series of publications which arose from a Symposium held at the Unilever Centre for Molecular Informatics at the University of Cambridge to celebrate the lifetime achievements of Peter Murray-Rust. One of the motives of Peter's work was and is a better transport and preservation of data and information in scientific publications. In both respects the following publication is relevant: it is about public data and their representation, and the publication represents a non-standard experiment of transporting the content of the scientific presentation. As you will see, it consists of the original slides used by Dan Zaharevitz in his talk "Adventures in Public Data" at the Unilever Centre together with a diligent transcript of his speech. The transcribers have gone through great effort to preserve the original spirit of the talk by preserving colloquial language as it is used at such occasions. For reasons known to us, the original speaker was unable to submit the manuscript in a more conventional form. We, the Editors, have discussed in depth whether such a format is suitable for a scientific journal. We have eventually decided to publish this "as is". We did this mostly because it was Peter's wish that this talk was published in this form and because we agreed with his notion that this format transmits the message just as well as a formal article as defined by our instructions for authors. We, the Editors, wish to make clear however that this is an exception that we made because we would like to preserve the temporal unity and message of this set of publications. Insisting on a formal publication would have meant losing this historical account as part of the thematic series of papers or disrupting the series. We hope that this will find the consent of our readership. PMID:22017861

Adventures in public data.

PubMed

Zaharevitz, Dan W

2011-10-14

This article contains the slides and transcript of a talk given by Dan Zaharevitz at the "Visions of a Semantic Molecular Future" symposium held at the University of Cambridge Department of Chemistry on 2011-01-19. A recording of the talk is available on the University Computing Service's Streaming Media Service archive at http://sms.cam.ac.uk/media/1095515 (unfortunately the first part of the recording was corrupted, so the talk appears to begin at slide 6, 'At a critical time'). We believe that Dan's message comes over extremely well in the textual transcript and that it would be poorer for serious editing. In addition we have added some explanations and references of some of the concepts in the slides and text. (Charlotte Bolton; Peter Murray-Rust, University of Cambridge) EDITORIAL PREFACE: The following paper is part of a series of publications which arose from a Symposium held at the Unilever Centre for Molecular Informatics at the University of Cambridge to celebrate the lifetime achievements of Peter Murray-Rust. One of the motives of Peter's work was and is a better transport and preservation of data and information in scientific publications. In both respects the following publication is relevant: it is about public data and their representation, and the publication represents a non-standard experiment of transporting the content of the scientific presentation. As you will see, it consists of the original slides used by Dan Zaharevitz in his talk "Adventures in Public Data" at the Unilever Centre together with a diligent transcript of his speech. The transcribers have gone through great effort to preserve the original spirit of the talk by preserving colloquial language as it is used at such occasions. For reasons known to us, the original speaker was unable to submit the manuscript in a more conventional form. We, the Editors, have discussed in depth whether such a format is suitable for a scientific journal. We have eventually decided to publish this "as is". We did this mostly because it was Peter's wish that this talk was published in this form and because we agreed with his notion that this format transmits the message just as well as a formal article as defined by our instructions for authors. We, the Editors, wish to make clear however that this is an exception that we made because we would like to preserve the temporal unity and message of this set of publications. Insisting on a formal publication would have meant losing this historical account as part of the thematic series of papers or disrupting the series. We hope that this will find the consent of our readership.

EDITORIAL: Incoming Editor-in-Chief Incoming Editor-in-Chief

NASA Astrophysics Data System (ADS)

Birch, David

2012-01-01

It is a pleasure and an honour for me to be taking over as Editor-in-Chief of Measurement Science and Technology. MST is well known across research communities worldwide as a leading journal in which to publish new techniques and instrumentation. It has gained this enviable position largely because of the excellent guidance of its Editorial Board and dedicated staff at Institute of Physics Publishing over many years. I want to highlight in particular the contribution of the outgoing Editor Peter Hauptmann, and other Editors before him, in making the journal truly international. We thank Peter immensely for all his hard work in leading the journal, having exceptionally served two terms, each of five years. I come into the post of Editor at a very interesting and challenging time for research. The global recession is leading to cuts in research funding in many countries, researchers and their outputs are coming under closer scrutiny than ever before, and more is being expected of them. Journals play a critical role in monitoring and maintaining research standards, but we should be careful not to assume that journal Impact Factor is the sole measure of research quality. Although expediency may sometimes demand it, Impact Factor, as practitioners know, is subject dependent. One of the great things about science and technology for me is its level playing field. The key point is still innovation no matter where the work is done or where it is published. MST has a long pedigree of being the natural home of the highest quality papers from leading researchers wishing to report novel instrumentation and techniques. 2013 will mark the 90th anniversary of MST and we look forward to celebrating in style its sustained success. I recall with pride the first paper I published in Journal of Physics E: Scientific Instruments (as MST was previously titled) back in 1977. The paper reported the design and application of an early fluorescence lifetime spectrometer that I had constructed for my PhD in the Department of Physics at the University of Manchester. Since that time I have witnessed many changes in instrumentation and techniques. I believe that I have been fortunate in not spending all of my time in a university. Having worked in or with industry throughout my career I have been able to see the trends from the perspective of both sectors. In my area of fluorescence spectroscopy I have seen the cost of systems fall in real terms, the performance rise, an increased need for user-friendly software and less emphasis on performance specification when customers decide which instrument to purchase. Such trends, no doubt replicated in other areas, reflect the migration of system instrumentation away from being the preserve of the specialist to much wider use and customization across the disciplines and skill-set. MST has embraced this change through its multidisciplinary remit in Special Features, Topical Reviews, Rapid Communications, Perspectives and regular Papers. These days there is much more of a partnership between industry and academia in research and this is to be applauded in these challenging times. I want to encourage contributions to MST from industry as well as academia, as MST is the ideal place to showcase the latest innovation from inception to commercial exploitation. Backed by one of the premier learned societies, the Institute of Physics, I have no doubt that MST will continue in its success and I look forward to helping to advance its high standing to even greater heights.

Proceedings of the European Conference on the Application of Polar Dielectrics (2nd) to Celebrate the Anniversary of the Dielectric Society (25th), Incorporating the International Workshop on Integrated Ferroelectrics (1st) Held in London (United Kingdom) on 12-15 April 1992

DTIC Science & Technology

1993-04-01

continuous streaking in the b -direction, possibly due to the twinned nature of the ferroelectic domains. The presence of a twinned domain structure has been...Box 211, Princeton, New Jersvey 08540. U. S. A ASSOCIATE ED)ITORS Peter Guinter Sidney B . Lang Koichi Tovoda In xtjtut hir Quaniei’rwhktriorik D...Oregon S. B . Lang (Pyroelectrics) EDITORIAL BOARD R pil Abcý Nagova. Japan Wi. Il ’ vwang. Auniclr. Germainy C. F. I’uilvari . Wa~shingiioi. DC( F

Highlights: Spring Council Meeting

NASA Astrophysics Data System (ADS)

Council members present at the May 24, 1981, meeting were Keiiti Aki, Steven Burges (for Jim Wallis), Peter S. Eagleson, E. R. Engdahl, Charles E. Helsley, James R. Heirtzler, Carl Kisslinger, Leslie H. Meredith, Chris N. K. Mooers, Norman F. Ness, Marcia M. Neugebauer, James J. O'Brien, Richard Rapp, Carl Sagan, James C. Savage, Joseph V. Smith, Fred Spilhaus, Donald L. Turcotte, James A. Van Allen, J. Tuzo Wilson, and Jay Winston (for Elmar R. Reiter until his arrival at 6:50 P.M.). David Strangway, representing the Canadian Geophysical Union, and Peter Steinhauser, representing the European Geophysical Society, were special observers at the meeting. Council meetings are open, and a number of section secretaries, committee chairmen, journal editors, and other members attended. The following major actions were adopted by the Council:The experiment of publishing oceanography and lower-atmosphere papers in JGR Green issues alternate to those containing upper-atmosphere papers will be continued through 1982. From preliminary indications the experiment seems to be working, but a full year of data, including a renewal cycle, is needed to assess the success of the experiment. Final decision will be made prior to the 1983 dues notices.

Might Astrobiological Findings Evoke a Religious Crisis?

NASA Astrophysics Data System (ADS)

Peters, T.; Froehlig, J. L.

2009-12-01

What might be the likely impact of confirmed discovery of extraterrestrial life—microbial or intelligent life—on terrestrial religion? Many have speculated that the anthropo-centrism and earth-centrism which allegedly have characterized our religious traditions would be confronted with a crisis. Would new knowledge that we are not alone in the universe lead to a collapse of traditional religious belief? This presentation will summarize the results of the Peters Religious Crisis Survey of 1325 respondents. This survey shows that the majority of adherents to Christianity, Islam, Judaism, and Buddhism demonstrate little or no anxiety regarding the prospect of contact with extraterrestrial life, even if they express some doubts regarding their respective religious tradition and the traditions of others. This presentation will also show that theological speculation regarding other worlds has sparked lively debate beginning as far back as the middle ages and continuing into our present era. Ted Peters is a research and teaching scholar with the Center for Theology and the Natural Sciences at the Graduate Theological Union in Berkeley, California. He is co-editor of the journal, Theology and Science, and author of the books, The Evolution of Terrestrial and Extraterrestrial Life (Pandora 2008) and Playing God? Genetic Determinism and Human Freedom (Routledge, rev. ed., 2003).

GR 20 parallel session A3: modified gravity

NASA Astrophysics Data System (ADS)

Hořava, Petr; Mohd, Arif; Melby-Thompson, Charles M.; Shawhan, Peter

2014-05-01

The parallel session (A3), on "Modified Gravity", enjoyed one on the largest number of abstract submissions (over 80), resulting in the selection of 24 oral presentations. The three short papers presented in the following sections are based on the session talks by Arif Mohd on thermodynamics of universal horizons in Einstein-Æther theory, Conformal anomalies in Hořava-Lifshitz gravity by Charles Melby-Thompson and detectability of scalar gravitational waves by LIGO and Virgo by Peter Shawhan. They have been selected as a representative sample, to illustrate some of the best in the remarkable and encouraging variety of topics discussed in the session—ranging from highly theoretical, to phenomenological, observational, and experimental—with all these areas playing an integral part in our quest to understand the limits of standard general relativity.

Home dialysis in the new USA bundled payment plan: implications and impact.

PubMed

Golper, Thomas A; Guest, Steven; Glickman, Joel D; Turk, Joe; Pulliam, Joseph P

2011-01-01

On 1 January 2011, a new payment system for Medicare patients will be implemented in the United States. This new system bundles services previously charged separately and under a "fee for service" environment. The authors discuss the implications of this approach. Over the next several pages is a response by American physicians and dialysis innovators to a federal initiative to change the way dialysis is paid for in the United States. Peter Blake, the Editor-in-Chief of Peritoneal Dialysis International, invited Thomas Golper to articulate physicians' concerns with this new payment scheme. After the government of the USA closed its comment period over the new payment methodology, called "bundling," Golper sought out colleagues from diverse backgrounds and compiled this collective view of the situation.

ProCure21+ should speed scheme starts.

PubMed

Baillie, Jonathan

2010-11-01

This October saw the launch of the new ProCure21+ National Framework under which, the Department of Health (DH) team behind the new scheme claims, the NHS can potentially save a further pound 200 million of public money on top of the substantial sums saved under predecessor, ProCure21, via faster, more streamlined procurement, design, planning, and construction, of publicly-funded healthcare schemes. HEJ editor Jonathan Baillie discussed, with the DH's senior responsible officer (SRO) and P21+ team leader Peter Sellars, the background to the new Framework's introduction, the success of its forerunner, and the additional benefits that ProCure21 + (which is backed by organisations incuding HM Treasury, the National Audit Office, and the Office of Government Commerce) should bring to the entire healthcare building supply chain.

Hydrogeology Journal in 2002

USGS Publications Warehouse

Olcott, Perry; Schneider, Robert; Voss, Clifford

2003-01-01

Hydrogeology Journal appeared in six issues containing a total of 674 pages and 47 major articles, including 22 Papers and 24 Reports, as well as Technical Notes and Book Reviews. The final issue of 2002 also contained the annual volume index. Hydrogeology Journal (HJ) is an international forum for hydrogeology and related disciplines. Authors in 2002 were from about 30 countries. Articles advanced hydrogeologic science and described hydrogeologic systems in many regions worldwide. These articles focused on 22 countries: Afghanistan, Argentina, Australia, Austria, Belgium, Brazil, Canada, China, India, Israel, Japan, Jordan, Mexico, New Zealand, Nigeria, Portugal, Qatar, Switzerland, Syria, Turkey, UK, and the USA. The Guest Editors of the 2002 HJ theme issue on "Groundwater Recharge", Bridget R. Scanlon and Peter G. Cook, assembled a highly relevant and sought-after collection of papers from eminent authors on wide-ranging aspects of the subject.

PREFACE: VII Brazilian Congress on Metrology (Metrologia 2013)

NASA Astrophysics Data System (ADS)

Costa-Félix, Rodrigo; Bernardes, Americo; Valente de Oliveira, José Carlos; Mauro Granjeiro, José; Epsztejn, Ruth; Ihlenfeld, Waldemar; Smarçaro da Cunha, Valnei

2015-01-01

SEVENTH BRAZILIAN CONGRESS ON METROLOGY (METROLOGIA 2013) Metrology and Quality for a Sustainable Development From November 24th to 27th 2013 was issued the Seventh Brazilian Congress on Metrology (Metrologia 2013), which is a biannual conference organized and sponsored by the Brazilian Society of Metrology (SBM) and the Brazilian National Institute of Metrology, Quality and Technology (Inmetro). This edition was held in the charming and historical city of Ouro Preto, MG, Brazil, and aimed to join people and institutions devoted to the dissemination of the metrology and conformity assessment. The Metrologia 2013 Conference consisted of Keynote Speeches (7) and regular papers (204). Among the regular papers, the 47 most outstanding ones, comprising a high quality content on Metrology and Conformity Assessment, were selected to be published in this issue of the Journal of Physics: Conference Series. The topics of the conference covered all important areas of Metrology, which were agglutinated in the following sessions in the present issue: . Physical Metrology (Acoustics, Vibration and Ultrasound; Electricity and Magnetism; Mechanics; Optics); . Metrology on Ionizing Radiations; . Time and Frequency; . Chemistry Metrology; . Materials Metrology; . Biotechnology; . Uncertainty, Statistics and Mathematics; . Legal Metrology; . Conformity Assessment. It is our great pleasure to present this volume of IOP Journal of Physics: Conference Series (JPCS) to the scientific community to promote further research in Metrology and related areas. We believe that this volume will be both an excellent source of scientific material in the fast evolving fields that were covered by Metrologia 2013. President of the congress Americo Bernardes Federal University of Ouro Preto atb@iceb.ufop.br Editor-in-chief Rodrigo Costa-Félix Brazilian National Institute of Metrology, Quality and Technology rpfelix@inmetro.gov.br Editors José Carlos Valente de Oliveira (Editor on Mechanical Metrology) Brazilian National Institute of Metrology, Quality and Technology jcoliveira@inmetro.gov.br José Mauro Granjeiro (Editor on Biotechnology) Brazilian National Institute of Metrology, Quality and Technology jmgranjeiro@inmetro.gov.br Ruth Epsztejn (Editor on Conformity Assessment) Brazilian National Institute of Metrology, Quality and Technology repsztejn@inmetro.gov.br Waldemar Ihlenfeld (Editor on Electrical Metrology) Brazilian National Institute of Metrology, Quality and Technology wgihlenfeld-pronametro@inmetro.gov.br Valnei Smarçaro da Cunha (Editor on Chemistry Metrology) Brazilian National Institute of Metrology, Quality and Technology vscunha@inmetro.gov.br Technical and Scientific Committee for Metrologia 2013 Ado Jório (UFMG) Carlos Achete (UFRJ, Inmetro) Flávio Vasconcelos (UFMG) Giorgio Moscati (USP) Hans Peter Grieneisen (Inmetro) Humberto Brandi (Inmetro) José Carlos Valente de Oliveira (Inmetro) José Guilherme Pereira Peixoto (IRD) José Mauro Granjeiro (Inmetro) Luiz Claudio Moreira Paschoal (Petrobras) Luis Fernado Rust (Inmetro) Luiz Silva Mello (PUC RJ) Marcos Nogueira Eberlin (Unicamp) Oleksii Kuznetsov (Inmetro) Regis Landim (Inmetro) Ricardo Carvalho (ON) Rodrigo Costa-Felix (Inmetro) Romeu José Daroda (Inmetro) Ruth Epsztejn (Inmetro) Valnei Smarçaro da Cunha (Inmetro) Valter Aibe (Inmetro) Waldemar Guilherme Kürten Ihlenfeld (PTB) Wanderley de Souza (UFRJ, Inmetro)

EDITORIAL: Message from the Editor Message from the Editor

NASA Astrophysics Data System (ADS)

Thomas, Paul

2010-02-01

This year Nuclear Fusion celebrates its fiftieth anniversary. This has been marked by the January special edition, containing papers presented at the plenary and celebratory evening session of the 22nd Fusion Energy Conference at Geneva. These papers underline the enormous progress that has been made in the last 50 years both in experiment and theory. Whilst the technical challenges that we face are still formidable, they are largely concerned with engineering a fusion reactor rather than fundamental plasma physics. In my editorial of a year ago, I remarked on the price of oil and the incentive that it gives to develop nuclear fusion into a viable energy source. This last year, attention has shifted somewhat from the markets to the environment and the Copenhagen climate summit in particular. The timescale for action on the environment is much shorter than we can possibly match and so we can only play our part towards developing long term solutions. Our responsibility is to present a programme that has the clear goal in developing a sustainable source of energy and, as the next step, make an unambiguous success of ITER. The Nuclear Fusion journal has continued to make an important contribution to the research programme and has maintained its position as the leading journal in the field. The journal depends entirely on its authors and referees and so I would like to thank them all for their work in 2009 and look forward to a continuing, successful collaboration in 2010. Refereeing The Nuclear Fusion Editorial Office understands how much effort is required of our referees. The Editorial Board decided that an expression of thanks to our most loyal referees is appropriate and so, since January 2005, we have been offering the top ten most active referees over the past year a personal subscription to Nuclear Fusion with electronic access for one year, free of charge. This year, seven of the top referees have reviewed four or more manuscripts in the period November 2008 to November 2009 and provided particularly detailed advice to the authors. The other three have been very helpful in 'minority fields'. We have excluded our Board members, Guest Editors of special editions and those referees who were already listed in the last four years. Guest Editors' work on papers submitted to their Special Issues is also excluded from consideration. The following people have been selected: Tomonori Takizuka, JAEA-Naka Fusion Institute, Japan Rudolf Neu, Max-Planck-Institut für Plasmaphysik, Germany Sibylle Guenter, Max-Planck-Institut für Plasmaphysik, Germany Taik-Soo Hahm, Princeton Plasma Physics Laboratory, United States David R. Mikkelsen, Princeton Plasma Physics Laboratory, United States Peter C. de Vries, EURATOM/UKAEA Fusion Association, United Kingdom Yasuhiro Suzuki, National Institute for Fusion Science, Japan Jerzy Wolowski, Institute of Plasma Physics and Laser Microfusion, Poland Tetsuo Tanabe, Kyushu University, Japan Yasuyuki Yagi, National Institute of Advanced Industrial Science and Technology, Japan Congratulations and many, many thanks! The Guest Editors of special editions deserve a special mention for the excellent help that they have given us. They are: Taik-Soo Hahm, Princeton Plasma Physics Laboratory, United States, Special Issue on H-Mode Physics and Transport Barriers Yaroslav Kolesnichenko, Institute for Nuclear Research, Ukraine, Special Issue on Energetic Particles in Magnetic Confinement Systems Kimitaka Itoh, National Institute for Fusion Science, Japan and Howard R. Wilson, University of York, UK, Special Issue on Plasma Instabilities Bernhard Unterberg, Forschungszentrum Juelich, Germany, Special Issue on Stochastic Fusion Plasma In addition, there is a group of several hundred referees who have helped us in the past year to maintain the high scientific standard of Nuclear Fusion. At the end of this issue we give the full list of all referees for 2009. Our thanks to them! Authors The winner of the 2009 Nuclear Fusion award was Steven A. Sabbagh et al for the paper entitled 'Resistive wall stabilized operation in rotating high beta NSTX plasmas' (Nucl. Fusion 46 635-644). Reviews Last year I announced a revival of Nuclear Fusion Reviews, following a decision by the Board of Editors. 'A review of zonal flow experiments', by Akihide Fujisawa was the first fruit of this. In 2010, we are expecting to publish further review articles, the first of which is entitled 'Gyrokinetic simulations of turbulent transport' by Xavier Garbet, Yasuhiro Idomura, Laurent Villard and Tomo-Hiko Watanabe. Letters At the 2009 Board of Editors Meeting in Atlanta, the current letters procedure was summarized and it was noted that the peer review time for Letters is quite variable. Some are accepted within a month of submission, others take longer. Since the purpose of Letters is to provide a route for rapid communication, this is quite an important matter. It was agreed that the Board of Editors would play a more active role in the Letter approval process. If a reviewer asks for a second revision the Editor or a Board of Editors member will be queried as to whether the submission should still be treated as a Letter rather than a regular Paper. The Board of Editors The following Board of Editors members reached the end of their term in 2009: Amanda Hubbard, Yaroslav Kolesnichenko, Kunioki Mima, Boris Sharkov and Michael Ulrickson. On behalf of the Nuclear Fusion Office and the Chairman of the Board of Editors, Mitsuru Kikuchi, I would like to thank them for their efforts in support of the journal. At the same time, we welcomed: Hiroshi Azechi, Xuru Duan, Richard Hawryluk, Sergey Konovalov, Bruce Lipschultz, Peter Norreys, Francesco Romanelli, Tony Taylor and Hartmut Zohm. I am sure that such an illustrious group does not need any introduction to the readers of Nuclear Fusion and I am confident that the new members can only further the success of the journal. It is with great sadness that I have to note the passing away of the following former members of the Board of Editors: Ravindra Sudan (1975 to 1984), Joe Di Marco (1984 to 1991) and Roy Bickerton (1975 to 1986). The Nuclear Fusion Office and IOP Publishing Just as the journal depends on the authors and referees, so its success is also due to the tireless and largely unsung efforts of the Nuclear Fusion Office in Vienna and IOP Publishing in Bristol. I would like to express my personal thanks to Maria Bergamini-Roedler, Katja Haslinger, Sophy Le Masurier, Yasmin McGlashan, Caroline Wilkinson, Sarah Ryder, Rachael Kriefman and Katie Gerrard for the support that they have given to me, the authors and the referees. Season's Greetings The January special edition delayed this editorial for a month. Nevertheless, I would like belatedly to wish our readers, authors, referees and Board of Editors the season's greetings and thank them for their contributions to Nuclear Fusion in 2009.

Nova Mus 2008 = QY Mus

NASA Astrophysics Data System (ADS)

Templeton, Matthew R.

2008-10-01

Nova Mus 2008 = QY Mus was discovered by William Liller, Vina del Mar, Chile, on 2008 September 28.998 UT at magnitude 8.6 (Tech Pan film + orange filter). The position is RA = 13h 16m 36.44s , Dec = -67d 36m 47.8s (from P. Nelson). This object was announced as a nova in IAU Circular 8990 (Daniel W.E. Green, editor). The nova classification was determined using low-resolution spectra by W. Liller indicating the presence of broad H-alpha lines at least 2300 angstroms wide. Several observers confirmed the nova and provided photometry. The position above was provided by Peter Nelson (Ellinbank, Vic., Aus.), and is averaged from four separate exposures (rms error approx. 0.4 arcseconds). The GCVS team have formally designated Nova Mus 2008 as QY MUS. Observations should be reported to the AAVSO International Database as QY MUS.

Medicus Petrus Hispanus (c1205-77 Peter of Spain): a XIII century Pope and Author of a Medieval Sex Guide.

PubMed

Ambrose, Charles T

2013-05-01

Petrus Hispanus was the only practicing physician ever to become Pope (1276-77). By all accounts he was an interim choice when rival French and Italian Cardinals could not elect one of their own nationality. Although not clearly responsible for any major political actions by the Church, Petrus was famous for several centuries after his death because of his secular writings - a text on logic (Summulae logicales) and a handbook on medicine (Thesaurus pauperum). The latter is noteworthy because it contains two sections on coitus - how to enhance the sexual act and how to subdue sexual urges. Promoting coitus seems an odd topic for a medieval Catholic cleric-writer and raises the question as to whether the first section may have been added by a later copyist or editor, but an examination of a very early manuscript of the Thesaurus gives assurance that the two sexual sections were written by Petrus, probably around 1270.

Keeping them connected--reducing drug-related harm in Australian schools from a Catholic perspective.

PubMed

Norden, Peter

2008-07-01

In this Harm Reduction Digest, Father Peter Norden of Jesuit Social Services (Australia) summarises the findings of a report of a consultation into how Catholic schools in Australia address substance use by school students. The report showed that while in the past the 'zero tolerance' approach had been the norm, more recently there had been a growing awareness in Catholic schools that it is possible to respond to the needs of drug-using students while being respectful of the duty of care to other students. Moreover, harm reduction was accepted as a serious objective for drug policy and practice in Australian Catholic schools. The paper canvases the key issues that emerged from the consultation and suggests what 'good practice' looks like, providing useful guidance for both Catholic and non-Catholic schools alike. For those of us outside the Catholic school system, the paper provides an enlightening read about how substance use can be best addressed within schools. Simon Lenton Editor, Harm Reduction Digest.

Astrophysical implications of extraterrestrial materials: A special issue for Ernst K. Zinner

NASA Astrophysics Data System (ADS)

Nittler, Larry R.

2018-01-01

This special issue is dedicated to the memory of Dr. Ernst K. Zinner (Fig. 1). Dr. Zinner (1937-2015) was a pioneer in the use of Secondary Ion Mass Spectrometry (SIMS) in geo- and cosmochemistry. His contributions to science were vast, but in addition to his foundational SIMS development work, he is best known for the discovery and detailed characterization of presolar stardust grains in meteorites. This discovery opened up important new connections between astrophysics and meteoritical research and this is the overarching theme of this issue. Throughout his career, Ernst was a teacher, mentor, friend, and generous collaborator to legions of scientists. This issue presents research by many who were taught by, inspired by, and/or collaborated with this innovative cosmochemist and astrophysicist. In addition to the author, Ernst's former students and collaborators Drs. Christine Floss (Washington University) Peter Hoppe (MPI for chemistry, Mainz, Germany), and Kevin McKeegan (University of California, Los Angeles) served as Guest Editors for this issue.

PREFACE: 31st European Physical Society Conference on Plasma Physics

NASA Astrophysics Data System (ADS)

Dendy, Richard

2004-12-01

This special issue of Plasma Physics and Controlled Fusion comprises refereed papers contributed by invited speakers at the 31st European Physical Society Conference on Plasma Physics. The conference was jointly hosted by the Rutherford Appleton Laboratory, by the EURATOM/UKAEA Fusion Association and by Imperial College London, where it took place from 28 June to 2 July 2004. The overall agenda for this conference was set by the Board of the Plasma Physics Division of the European Physical Society, chaired by Friedrich Wagner (MPIPP, Garching) and his successor Jo Lister (CRPP, Lausanne). It built on developments in recent years, by further increasing the scientific diversity of the conference programme, whilst maintaining its depth and quality. A correspondingly diverse Programme Committee was set up, whose members are listed below. The final task of the Programme Committee has been the preparation of this special issue. In carrying out this work, as in preparing the scientific programme of the conference, the Programme Committee formed specialist subcommittees representing the different fields of plasma science. The chairmen of these subcommittees, in particular, accepted a very heavy workload on behalf of their respective research communities. It is a great pleasure to take this opportunity to thank: Emilia R Solano (CIEMAT, Madrid), magnetic confinement fusion; Jürgen Meyer-ter-Vehn (MPQ, Garching), laser-plasma interaction and beam plasma physics; and Jean-Luc Dorier (CRPP, Lausanne), dusty plasmas. The relatively few papers in astrophysical and basic plasma physics were co-ordinated by a small subcommittee which I led. Together with Peter Norreys (RAL, Chilton), we five constitute the editorial team for this special issue. The extensive refereeing load, compressed into a short time interval, was borne by the Programme Committee members and by many other experts, to whom this special issue owes much. We are also grateful to the Local Organizing Committee chaired by Henry Hutchinson (RAL, Chilton), and to the Plasma Physics and Controlled Fusion journal team (Institute of Physics Publishing, Bristol), for their work on this conference. At the 2004 European Physical Society Conference on Plasma Physics, plenary invited speakers whose talks spanned the entire field were followed, each day, by multiple parallel sessions which also included invited talks. Invited speakers in both these categories were asked to contribute papers to this special issue (the contributed papers at this conference, and at all recent conferences in this series, are archived at http://epsppd.epfl.ch). The Programme Committee is very grateful to the many invited speakers who have responded positively to this request. Invited papers appear here in their order of presentation during the week beginning 28 June 2004; this ordering provides an echo of the character of the conference, as it was experienced by those who took part. Programme Committee 2004 Professor Richard Dendy UKAEA Culham Division, UK Chairman and guest editor Dr Jean-Luc Dorier Centre de Recherches en Physique des Plasmas, Lausanne, Switzerland (Co-ordinator of dusty plasmas and guest editor) Professor Jürgen Meyer-ter-Vehn Max-Planck-Institut für Quantenoptik, Garching, Germany (Co-ordinator of laser-plasma interaction and beam plasma physics and guest editor) Dr Peter Norreys Rutherford Appleton Laboratory, Chilton, UK (Scientific Secretary and guest editor) Dr Emilia R Solano CIEMAT Laboratorio Nacional de Fusión, Madrid, Spain ( Co-ordinator of magnetic confinement fusion and guest editor) Dr Shalom Eliezer Soreq Nuclear Research Centre, Israel Dr Wim Goedheer FOM-Instituut voor Plasmafysica, Rijnhuizen, Netherlands Professor Henry Hutchinson Rutherford Appleton Laboratory, Chilton, UK Professor John Kirk Max-Planck-Institut für Kernphysik, Heidelberg, Germany Dr Raymond Koch Ecole Royale Militaire/Koninklijke Militaire School, Brussels, Belgium Professor Gerrit Kroesen Technische Universiteit Eindhoven, Netherlands Dr Martin Lampe Naval Research Laboratory, Washington DC, USA Dr Jo Lister Centre de Recherches en Physique des Plasmas, Lausanne, Switzerland Dr Paola Mantica Istituto di Fisica del Plasma, Milan, Italy Professor Tito Mendonca Instituto Superior Tecnico, Lisbon, Portugal Dr Patrick Mora École Polytechnique, Palaiseau, France Professor Lennart Stenflo Umeå Universitet, Sweden Professor Paul Thomas CEA Cadarache, Saint-Paul-lez-Durance, France Professor Friedrich Wagner Max-Planck-Institut fr Plasmaphysik, Garching, Germany Professor Hannspeter Winter Technische Universität Wien, Austria

Theories of Power, Poverty, and Law: In Commemoration of the Contributions of Peter Bachrach--Power, Law, and Final Thoughts: The Contributions of Peter Bachrach

ERIC Educational Resources Information Center

Schneider, Elizabeth M.

2010-01-01

I am pleased to be part of this symposium to celebrate the life and work of Peter Bachrach. Although my focus is the relevance of Peter's ideas of power to law, I want to begin with some personal comments as well as raise some final thoughts, drawing on others' contributions. Like so many of Peter's other students, I adored him. Peter's joy in…

Genetics Home Reference: Peters plus syndrome

MedlinePlus

... Facebook Twitter Home Health Conditions Peters plus syndrome Peters plus syndrome Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Peters plus syndrome is an inherited condition that is ...

Density Scaling of Glassy Dynamics and Dynamic Heterogeneities in Glass-forming Liquids.

NASA Astrophysics Data System (ADS)

Hu, Yuan-Chao; Yang, Yong; Wang, Wei-Hua

The discovery of density scaling in strongly correlating systems is an important progress for understanding the dynamic behaviors of supercooled liquids. Here we found for a ternary metallic glass-forming liquid, it is not strongly correlating thermodynamically, but its average dynamics, dynamic heterogeneities and static structure are still well described by density scaling with the same scaling exponent γ. As an intrinsic material constant stemming from the fundamental interatomic interactions, γ is theoretically predicted from the thermodynamic fluctuations of potential energy and the virial. Although γ is conventionally understood merely from the repulsive part of the inter-particle potentials, the strong correlation between γ and the Grüneisen parameter up to the accuracy of the Dulong-Petit approximation demonstrates the important roles of anharmonicity and attractive force of the interatomic potential in governing glass transition of metallic glass-formers. The supercooled dynamics and density scaling behaviors will also be discussed in model glass-forming liquids with tunable attractive potentials to further quantify the nonperturbative roles of attractive interactions. We acknowledge the support from ''Peter Ho Conference Scholarships'' of City University of Hong Kong.

Short stature, brachydactyly, and Peters' anomaly (Peters'-plus syndrome): confirmation of autosomal recessive inheritance.

PubMed Central

de Almeida, J C; Reis, D F; Llerena Júnior, J; Barbosa Neto, J; Pontes, R L; Middleton, S; Telles, L F

1991-01-01

Two sibs with a phenotype characterised by short stature, brachydactyly, and ocular anomalies (Peters' anomaly) are reported (Peters'-plus syndrome). The consanguinity is in agreement with the proposed autosomal recessive inheritance. Images PMID:1856836

Retraction Statement: "Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL" by Xue Li, MMed, Dong Li, PhD, Yong Zhuang, MMed, Qing Shi, BSc, Wei Wei, MMed, and Xiuli Ju, MD, PhD.

PubMed

2017-05-01

The above article, published online 23 August 2013 in Pediatric Blood and Cancer, Volume 60, Issue 12, December 2013, Pages 2060-2067, has been retracted by agreement among the authors, the journal's Editor-in-Chief, Peter E. Newburger, M.D., and Wiley Periodicals, Inc. The decision to retract was agreed upon following notification that the paper substantially duplicates a prior study already published in Chinese https://www.ncbi.nlm.nih.gov/pubmed/23611221. The authors were not aware that publication in another language would constitute a duplicate publication and, upon being informed of this fact, have agreed to withdraw the paper from Pediatric Blood and Cancer. Reference Li X, Li D, Zhuang Y, Shi Q, Wei W and Ju X. Overexpression of miR-708 and its targets in the childhood common precursor B-cell ALL. Pediatr Blood Cancer. 2013; 60: 2060-2067. doi:10.1002/pbc.24583. © 2017 Wiley Periodicals, Inc.

Toward A New Evolutionary Synthesis.

PubMed

Flannery, Michael A

2017-01-01

This essay responds to Peter T. Saunders's call to go Beyond the neo-Darwinist Paradigm. While there is much to commend in his analysis, especially his suggestion that the extended evolutionary synthesis (EES) may not go far enough, he leaves the question of whether this should involve mere revision or total replacement open. A historiographical review reveals significant problems stemming from certain positivist assumptions and commitments within neo-Darwinian orthodoxy and the EES over and above any scientific considerations. As such, mere tweaking of the existing paradigm or its extension will do little to remedy the intellectual prejudices currently plaguing it. A complete overhaul is suggested by applying the López Ontological Demarcation Design (LODD) principle with biology in a multidisciplinary, non-reductionist philosophical framework. Building on the concept of Organismic-Systems Biology (OSB), a component of General Systems Theory (GTS) associated with polymathic biologist Ludwig von Bertalanffy (1901-1972), and cosmic evolution (CE) proposed by UCLA philosopher John Elof Boodin (1869-1950), the outline of a new evolutionary synthesis is offered as a prolegomenon to further study and evaluation. Copyright: © 2016 by Fabrizio Serra editore, Pisa · Roma.

The Travails of Criticality: Understanding Peter McLaren's Revolutionary Vocation. An Article Review of Peter McLaren, "Pedagogy of Insurrection" (New York: Peter Lang, 2015)

ERIC Educational Resources Information Center

Baldacchino, John

2017-01-01

This is an article review of Peter McLaren's "Pedagogy of Insurrection" (New York: Peter Lang, 2015). While it seeks to position McLaren's work within the context of critical pedagogy, this paper also assesses McLaren from the wider discussion of Marxist--Hegelian discourse as it evolved within the Left. Engaging with McLaren critically,…

R. S. Peters and the Periphery

ERIC Educational Resources Information Center

Haynes, Bruce

2013-01-01

Paul Hirst claimed that Richard Peters "revolutionised philosophy of education". This does not accord with my experience in the Antipodean periphery. My experience of the work of Wittgenstein, Austin and Kovesi before reading Peters and Dewey, Kuhn and Toulmin subsequently meant that Peters was a major but not revolutionary figure in my…

Peter Wilcox: A new purple-skin, yellow flesh fresh market potato cultivar

USDA-ARS?s Scientific Manuscript database

Peter Wilcox is a new, medium-maturing, purple-skin, yellow-flesh potato cultivar for fresh market. Peter Wilcox also produces light-colored chips, although it is being released primarily as a fresh market potato because of its skin and flesh colors. Tubers of Peter Wilcox are attractive, smooth, wi...

Peter F. Green - Deputy Laboratory Director, Science and Technology |

Science.gov Websites

NREL Peter F. Green - Deputy Laboratory Director, Science and Technology Peter F. Green - Deputy Laboratory Director, Science and Technology A photo of Peter Green. Green came to NREL in August than 250 collaborative publications and 20 patent disclosures. Green also served as the B.F. Goodrich

THE JOURNAL OF THE CHIROPRACTIC & OSTEOPATHIC COLLEGE OF AUSTRALASIA

PubMed Central

Walker, Bruce F.

1998-01-01

The first edition of the Journal of the Chiropractic and Osteopathic College of Australasia was known as COMSIG Review and was published in November, 1992 to coincide with a large conference that COCA had organised in Melbourne. In the first few years the majority of articles were magazine style reviews, similar to these found in the Australian Family Physician. The first Editor was Bruce Walker and subsequent Editors have included John Drinkwater, Stephanie Campbell and John Reggars. The current Editors in Chief, Peter Tuchin and Henry Pollard, are staff members at Macquarie University, Centre of Chiropractic, with a strong background in science and research and both are currently undertaking post-graduate research degrees. Over several years the magazine review style was changed in keeping with a more full journal format. An Editorial Board was formed, comprised of chiropractors, osteopaths and medical practitioners, some of whom are world renowned in their particular field of research. By March, 1996 it was decided to change the name of the journal to Australasian Chiropractic and Osteopathy (ACO). This was a purposeful move to reflect the maturing of the journal and also the growth of the College and in the five years since November 1992, seventy-nine scientific articles have been published. It is anticipated that the journal will continue to be widely distributed throughout the world, with current subscriptions from all Australian undergraduate chiropractic and osteopathic institutions and the vast majority of international undergraduate institutions. ACO is currently indexed with Mantis (formerly Chirolars). The Editorial Panel continue to strive for Australasian Chiropractic and Osteopathy inclusion into Index Medicus and thereby Medline. However, it is recognised that readership of chiropractic journals is very low throughout the world and it is unlikely in the near future that any chiropractic journal other than the Journal of Manipulative and Physiological Therapeutics will be included in Index Medicus. The lack of mainstream international indexing will not stop or prevent the College from producing a first rate journal into the future years of the professions. In fact with the now steady growth in Australian chiropractic and osteopathic research, it is envisaged that ACO will be Australia's leading professional journal. We trust our membership enjoy reading the journal and find many of its articles instructional. We look forward to any comments from members relating to the production of the journal and any suggestions will be welcomed. PMID:17989763

Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers.

PubMed

Ye, Xin Cynthia; Ng, Isaiah; Seid-Karbasi, Puya; Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby; Wasserman, Wyeth W

2013-08-06

The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome, Cat Eye syndrome, Kabuki syndrome, Leigh syndrome, Peters anomaly, and Rothmund-Thomson syndrome. The editor progress score was used to measure performance for a portion of sites. The PFOND system provides a convenient and structured Internet resource for the facilitated creation of information resources for families confronted by rare disorders. The system empowers volunteers to participate in the creation of quality content, while allowing for the inevitable turnover of contributors over time. The next phase of PFOND development will focus on volunteer participation in system development and community engagement.

Portal for Families Overcoming Neurodevelopmental Disorders (PFOND): Implementation of a Software Framework for Facilitated Community Website Creation by Nontechnical Volunteers

PubMed Central

Imam, Tuhina; Lee, Cheryl E; Chen, Shirley Yu; Herman, Adam; Sharma, Balraj; Johal, Gurinder; Gu, Bobby

2013-01-01

Background The Portal for Families Overcoming Neurodevelopmental Disorders (PFOND) provides a structured Internet interface for the sharing of information with individuals struggling with the consequences of rare developmental disorders. Large disease-impacted communities can support fundraising organizations that disseminate Web-based information through elegant websites run by professional staff. Such quality resources for families challenged by rare disorders are infrequently produced and, when available, are often dependent upon the continued efforts of a single individual. Objective The project endeavors to create an intuitive Web-based software system that allows a volunteer with limited technical computer skills to produce a useful rare disease website in a short time period. Such a system should provide access to emerging news and research findings, facilitate community participation, present summary information about the disorder, and allow for transient management by volunteers who are likely to change periodically. Methods The prototype portal was implemented using the WordPress software system with both existing and customized supplementary plug-in software modules. Gamification scoring features were implemented in a module, allowing editors to measure progress. The system was installed on a Linux-based computer server, accessible across the Internet through standard Web browsers. Results A prototype PFOND system was implemented and tested. The prototype system features a structured organization with distinct partitions for background information, recent publications, and community discussions. The software design allows volunteer editors to create a themed website, implement a limited set of topic pages, and connect the software to dynamic RSS feeds providing information about recent news or advances. The prototype was assessed by a fraction of the disease sites developed (8 out of 27), including Aarskog-Scott syndrome, Aniridia, Adams-Oliver syndrome, Cat Eye syndrome, Kabuki syndrome, Leigh syndrome, Peters anomaly, and Rothmund-Thomson syndrome. The editor progress score was used to measure performance for a portion of sites. Conclusions The PFOND system provides a convenient and structured Internet resource for the facilitated creation of information resources for families confronted by rare disorders. The system empowers volunteers to participate in the creation of quality content, while allowing for the inevitable turnover of contributors over time. The next phase of PFOND development will focus on volunteer participation in system development and community engagement. PMID:23920006

Cloning and characterization of a heme oxygenase-2 gene from alfalfa (Medicago sativa L.).

PubMed

Fu, Guang-Qing; Jin, Qi-Jiang; Lin, Yu-Ting; Feng, Jian-Fei; Nie, Li; Shen, Wen-Biao; Zheng, Tian-Qing

2011-11-01

Heme oxygenase (HO, EC 1.14.99.3) catalyzes the oxidation of heme and performs vital roles in plant development and stress responses. Two HO isozymes exist in plants. Between these, HO-1 is an oxidative stress-response protein, and HO-2 usually exhibited constitutive expression. Although alfalfa HO-1 gene (MsHO1) has been investigated previously, HO2 is still poorly understood. In this study, we report the cloning and characterization of HO2 gene, MsHO2, from alfalfa (Medica sativa L.). The full-length cDNA of MsHO2 contains an ORF of 870 bp and encodes for 290 amino acid residues with a predicted molecular mass of 33.3 kDa. Similar to MsHO1, MsHO2 also appears to have an N-terminal transit peptide sequence for chloroplast import. Many conserved residues in plant HO were also conserved in MsHO2. However, unlike HO-1, the conserved histidine (His) required for heme-iron binding and HO activity was replaced by tyrosine (Tyr) in MsHO2. Further biochemical activity analysis of purified mature MsHO2 showed no HO activity, suggesting that MsHO2 may not be a true HO in nature. Semi-quantitative RT-PCR confirmed its maximum expression in the germinating seeds. Importantly, the expression levels of MsHO2 were up-regulated under sodium nitroprusside (SNP) and H(2)O(2) (especially) treatment, respectively.

Ferroelectricity and competing interactions in Ho-deficient non-stoichiometric orthorhombic HoMnO{sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J. X.; Yan, Z. B.; Xie, Y. L.

2015-05-07

We investigate the consequences of the Ho-deficient non-stoichiometry in orthorhombic HoMnO{sub 3} in terms of microscopic mechanisms for ferroelectricity modulation. It is suggested that the Ho-deficiency (then Mn excess) results in Ho-vacancies and then Mn occupation of the Ho-site with increasing non-stoichiometry. The Ho-deficiency enhances the Mn-Mn symmetric exchange striction by suppressing the independent Ho-Ho interaction, and thus benefits to the induced Ho spin ordering against the independent Ho spin ordering. The symmetric Ho-Mn exchange striction is thus enhanced by this induced Ho spin ordering, leading to remarkably enhanced ferroelectric polarization as observed. This work presents an alternative scheme tomore » modulate the multiferroicity in rare-earth manganites of strong 4f-3d coupling.« less

Citations Prize 2013

NASA Astrophysics Data System (ADS)

Cherry, Simon; Ruffle, Jon

2014-06-01

Physics in Medicine and Biology (PMB) awards its 'Citations Prize' to the authors of the original research paper that has received the most citations in the preceding five years (according to the Institute for Scientific Information (ISI)). The lead author of the winning paper is presented with the Rotblat Medal (named in honour of Professor Sir Joseph Rotblat, a Nobel Prize winner who also was the second—and longest serving—Editor of PMB, from 1961-1972). The winner of the 2013 Citations Prize for the paper which has received the most citations in the previous five years (2008-2012) is Figure. Figure. Four of the prize winning authors. From left to right: Thomas Istel (Philips), Jens-Peter Schlomka (with medal, MorphoDetection), Ewald Roessl (Philips), and Gerhard Martens (Philips). Title: Experimental feasibility of multi-energy photon-counting K-edge imaging in pre-clinical computed tomography Authors: Jens Peter Schlomka1, Ewald Roessl1, Ralf Dorscheid2, Stefan Dill2, Gerhard Martens1, Thomas Istel1, Christian Bäumer3, Christoph Herrmann3, Roger Steadman3, Günter Zeitler3, Amir Livne4 and Roland Proksa1 Institutions: 1 Philips Research Europe, Sector Medical Imaging Systems, Hamburg, Germany 2 Philips Research Europe, Engineering & Technology, Aachen, Germany 3 Philips Research Europe, Sector Medical Imaging Systems, Aachen, Germany 4 Philips Healthcare, Global Research and Advanced Development, Haifa, Israel Reference: Schlomka et al 2008 Phys. Med. Biol. 53 4031-47 This paper becomes the first to win both this citations prize and also the PMB best paper prize (The Roberts Prize), which it won for the year 2008. Discussion of the significance of the winning paper can be found in this medicalphysicsweb article from the time of the Roberts Prize win (http://medicalphysicsweb.org/cws/article/research/39907). The author's enthusiasm for their prototype spectral CT system has certainly been reflected in the large number of citations the paper subsequently has received. Our warm congratulations go to the winning authors.

The Federal Republic of Germany and Left Wing Terrorism

DTIC Science & Technology

2003-12-01

Stoll, Peter Jurgen Boock, Susan Albrecht, Rolf Clemens Wagner, and Stefan Wisniewski. 49 Merkl , p. 199. 50 Ibid, p. 192. 51 Hans-Joachim Klein...during each 2 Peter H. Merkl , “Rollerball or Neo-Nazi Violence?,” in Peter H. Merkl (ed...commitment to non-violence is hypocritical.”28 Peter Merkl described the situation best when he said, “Terrorism, of course is not the logical result of

The Ho-Ni-Ge system: Isothermal section and new rare-earth nickel germanides

NASA Astrophysics Data System (ADS)

Morozkin, A. V.; Knotko, A. V.; Yapaskurt, V. O.; Yuan, Fang; Mozharivskyj, Y.; Pani, M.; Provino, A.; Manfrinetti, P.

2015-05-01

The Ho-Ni-Ge system has been investigated at 1070 K and up to 60 at% Ho by X-ray diffraction and microprobe analyses. Besides the eight known compounds, HoNi5Ge3 (YNi5Si3-type), HoNi2Ge2 (CeAl2Ga2-type), Ho2NiGe6 (Ce2CuGe6-type), HoNiGe3 (SmNiGe3-type), HoNi0.2÷0.6Ge2 (CeNiSi2-type), Ho37÷34Ni6÷24Ge57÷42 (AlB2-type), HoNiGe (TiNiSi-type), Ho3NiGe2 (La3NiGe2-type), the ternary system contains four new compounds: Ho3Ni11Ge4 (Sc3Ni11Ge4-type), HoNi3Ge2 (ErNi3Ge2-type), Ho3Ni2Ge3 (Hf3Ni2Si3-type) and Ho5Ni2Ge3 (unknown structure). Quasi-binary solid solutions were observed at 1070 K for Ho2Ni17, HoNi5, HoNi7, HoNi3, HoNi2, HoNi and Ho2Ge3, but no detectable solubility was found for the other binary compounds in the Ho-Ni-Ge system. Based on the magnetization measurements, the HoNi5Ge3, HoNi3Ge2 and Ho3Ni11Ge4 (and isostructural {Tb, Dy}3Ni11Ge4) compounds have been found to show paramagnetic behavior down to 5 K, whereas Ho3Ni2Ge3 exhibits an antiferromagnetic transition at 7 K. Additionally, the crystal structure of the new isostructural phases {Y, Yb}Ni3Ge2 (ErNi3Ge2-type), Er3Ni11Ge4 (Sc3Ni11Ge4-type) and {Y, Tb, Dy, Er, Tm}3Ni2Ge3 (Hf3Ni2Si3-type) has been also investigated.

Ordovician conodonts and stratigraphy of the ST. Peter sandstone and glen wood shale, central United States

USGS Publications Warehouse

Witzke, B.J.; Metzger, R.A.

2005-01-01

The age of the St. Peter Sandstone in the central and northern Midcontinent has long been considered equivocal because of the general absence of biostratigraphically useful fossils. Conodonts recovered from the St. Peter Sandstone in Iowa, Minnesota, Nebraska, and Kansas for this study help place some age constraints on this renowned formation in its northern and western extent. Faunas from the lower St. Peter include Phragmodus flexuosus, Cahabagnathus sp., and Leptochirognathus sp., and a late Whiterockian (Chazyan) correlation is indicated. Juvenile or immature elements of P. flexuosus from these collections show morphologies trending toward P. cognitus and P. inflexus, and paedomorphic derivation of these latter species is proposed. Diverse assemblages of hyaline forms also occur in the St. Peter strata (Erismodus spp., Erraticodon sp., Curtognathus sp., Coleodus sp., Archeognathus sp., Stereoconus sp., others) along with various albid elements (Plectodina sp., Eoplacognathus sp., others). The overlying Glenwood Shale contains abundant conodonts dominated by Phragmodus cognitus, Erismodus sp., and Chirognathus duodactylus, and the fauna is interpreted as an early Mohawkian (Blackriveran) association. Certain thin shale units in the St. Peter-Glenwood succession represent condensed intervals, in part reflected by their exceptionally high conodont abundances. Some organic-rich phosphatic shale units in the lower St. Peter of western Iowa have produced equivalent yields of tens of thousands of conodonts per kilogram, and many Glenwood Shale samples yield thousands of conodonts per kilogram. Previous depositional models have proposed that the St. Peter is primarily a succession of littoral and nearshore facies forming a broadly diachronous transgressive sheet sand. However, broad-scale diachroneity cannot be demonstrated with available biostratigraphic control. The recognition of condensed marine shale units, phosphorites, ironstones, and pyritic hardgrounds in the western facies tract of the St. Peter Sandstone has necessitated a re-evaluation of previous regional models of St. Peter deposition. The St. Peter is interpreted to be a composite stratigraphic interval deposited during a succession of transgressive-regressive sedimentary cycles. Transgressive episodes in some cycles were marked by offshore sediment condensation or starvation within a stratified seaway.

Production and calving traits of Montbéliarde × Holstein and Viking Red × Holstein cows compared with pure Holstein cows during first lactation in 8 commercial dairy herds.

PubMed

Hazel, A R; Heins, B J; Hansen, L B

2017-05-01

Montbéliarde (MO) × Holstein (HO) and Viking Red (VR) × HO crossbred cows were compared with pure HO cows in 8 large, high-performance dairy herds. All cows were either 2-breed crossbred or pure HO cows that calved for the first time from December 2010 to April 2014. Best Prediction was used to calculate 305-d milk, fat, and protein production, as well as somatic cell score, and 513 MO × HO, 540 VR × HO, and 978 HO cows were analyzed for production in first lactation. Calving difficulty was scored from 1 (no assistance) to 5 (extreme difficulty). The analysis of calving traits included 493 MO × HO, 504 VR × HO, and 971 HO cows at first calving. Age at first calving was similar for breed groups, and the herds calved both crossbred (23.8 mo) and HO (23.9 mo) cows at young ages. The MO × HO crossbred cows had +3% higher production of 305-d fat plus protein production (actual basis, not mature equivalent) than the HO cows, and the VR × HO were similar to the HO cows for fat plus protein production. Breed groups did not differ for SCS during first lactation. The VR-sired 3-breed crossbred calves (from MO × HO dams) were similar to pure HO calves for calving difficulty; however, MO-sired male calves born to VR × HO dams had a mean score that was +0.5 points higher for calving difficulty than pure HO male calves. The 3-breed crossbred calves from both MO × HO (4%) and VR × HO (5%) first-lactation dams had a much lower stillbirth rate compared with pure HO calves (9%) from first-lactation dams. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly.

PubMed

Hanson, I M; Fletcher, J M; Jordan, T; Brown, A; Taylor, D; Adams, R J; Punnett, H H; van Heyningen, V

1994-02-01

Mutation or deletion of the PAX6 gene underlies many cases of aniridia. Three lines of evidence now converge to implicate PAX6 more widely in anterior segment malformations including Peters' anomaly. First, a child with Peters' anomaly is deleted for one copy of PAX6. Second, affected members of a family with dominantly inherited anterior segment malformations, including Peters' anomaly are heterozygous for an R26G mutation in the PAX6 paired box. Third, a proportion of Sey/+ Smalleye mice, heterozygous for a nonsense mutation in murine Pax-6, have an ocular phenotype resembling Peters' anomaly. We therefore propose that a variety of anterior segment anomalies may be associated with PAX6 mutations.

Simulation of ground-water flow in the St. Peter aquifer in an area contaminated by coal-tar derivatives, St. Louis Park, Minnesota. Water Resources Investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lorenz, D.L.; Stark, J.R.

1990-01-01

A model constructed to simulate ground-water flow in part of the Prairie du Chien-Jordan and St. Peter aquifers, St. Louis Park, Minnesota, was used to test hypotheses about the movement of ground water contaminated with coal-tar derivatives and to simulate alternatives for reducing the downgradient movement of contamination in the St. Peter aquifer. The model, constructed for a previous study, was applied to simulate the effects of current ground-water withdrawals on the potentiometric surface of the St. Peter aquifer. Model simulations predict that the multiaquifer wells have the potential to limit downgradient migration of contaminants in the St. Peter aquifermore » caused by cones of depression created around the multiaquifer wells. Differences in vertical leakage to the St. Peter aquifer may exist in areas of bedrock valleys. Model simulations indicate that these differences are not likely to affect significantly the general patterns of ground-water flow.« less

The Ho–Ni–Ge system: Isothermal section and new rare-earth nickel germanides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morozkin, A.V., E-mail: morozkin@tech.chem.msu.ru; Knotko, A.V.; Yapaskurt, V.O.

2015-05-15

The Ho–Ni–Ge system has been investigated at 1070 K and up to ~60 at% Ho by X-ray diffraction and microprobe analyses. Besides the eight known compounds, HoNi{sub 5}Ge{sub 3} (YNi{sub 5}Si{sub 3}-type), HoNi{sub 2}Ge{sub 2} (CeAl{sub 2}Ga{sub 2}-type), Ho{sub 2}NiGe{sub 6} (Ce{sub 2}CuGe{sub 6}-type), HoNiGe{sub 3} (SmNiGe{sub 3}-type), HoNi{sub 0.2÷0.6}Ge{sub 2} (CeNiSi{sub 2}-type), Ho{sub 37÷34}Ni{sub 6÷24}Ge{sub 57÷42} (AlB{sub 2}-type), HoNiGe (TiNiSi-type), Ho{sub 3}NiGe{sub 2} (La{sub 3}NiGe{sub 2}-type), the ternary system contains four new compounds: Ho{sub 3}Ni{sub 11}Ge{sub 4} (Sc{sub 3}Ni{sub 11}Ge{sub 4}-type), HoNi{sub 3}Ge{sub 2} (ErNi{sub 3}Ge{sub 2}-type), Ho{sub 3}Ni{sub 2}Ge{sub 3} (Hf{sub 3}Ni{sub 2}Si{sub 3}-type) and ~Ho{sub 5}Ni{sub 2}Ge{submore » 3} (unknown structure). Quasi-binary solid solutions were observed at 1070 K for Ho{sub 2}Ni{sub 17}, HoNi{sub 5}, HoNi{sub 7}, HoNi{sub 3}, HoNi{sub 2}, HoNi and Ho{sub 2}Ge{sub 3}, but no detectable solubility was found for the other binary compounds in the Ho–Ni–Ge system. Based on the magnetization measurements, the HoNi{sub 5}Ge{sub 3}, HoNi{sub 3}Ge{sub 2} and Ho{sub 3}Ni{sub 11}Ge{sub 4} (and isostructural (Tb, Dy){sub 3}Ni{sub 11}Ge{sub 4}) compounds have been found to show paramagnetic behavior down to 5 K, whereas Ho{sub 3}Ni{sub 2}Ge{sub 3} exhibits an antiferromagnetic transition at ~7 K. Additionally, the crystal structure of the new isostructural phases (Y, Yb)Ni{sub 3}Ge{sub 2} (ErNi{sub 3}Ge{sub 2}-type), Er{sub 3}Ni{sub 11}Ge{sub 4} (Sc{sub 3}Ni{sub 11}Ge{sub 4}-type) and (Y, Tb, Dy, Er, Tm){sub 3}Ni{sub 2}Ge{sub 3} (Hf{sub 3}Ni{sub 2}Si{sub 3}-type) has been also investigated. - Graphical abstract: The Ho–Ni–Ge system has been investigated at 1070 K and up to ~60 at.% Ho by X-ray and microprobe analyses. Besides the eight known compounds, i.e. HoNi{sub 5}Ge{sub 3} (YNi{sub 5}Si{sub 3}-type), HoNi{sub 2}Ge{sub 2} (CeAl{sub 2}Ga{sub 2}-type), Ho{sub 2}NiGe{sub 6} (Ce{sub 2}CuGe{sub 6}-type), HoNiGe{sub 3} (SmNiGe{sub 3}-type), HoNi{sub 0.2÷0.6}Ge{sub 2} (CeNiSi{sub 2}-type), Ho{sub 37÷34}Ni{sub 6÷24}Ge{sub 57÷42} (AlB{sub 2}-type), HoNiGe (TiNiSi-type), Ho{sub 3}NiGe{sub 2} (La{sub 3}NiGe{sub 2}-type), the ternary system contains four new compounds: Ho{sub 3}Ni{sub 11}Ge{sub 4} (Sc{sub 3}Ni{sub 11}Ge{sub 4}-type), HoNi{sub 3}Ge{sub 2} (ErNi{sub 3}Ge{sub 2}-type), Ho{sub 3}Ni{sub 2}Ge{sub 3} (Hf{sub 3}Ni{sub 2}Si{sub 3}-type) and ~Ho{sub 5}Ni{sub 2}Ge{sub 3} (unknown structure). Quasi-binary solid solutions were found to form at 1070 K from the binary Ho{sub 2}Ni{sub 17}, HoNi{sub 5}, HoNi{sub 7}, HoNi{sub 3}, HoNi{sub 2}, HoNi and Ho{sub 2}Ge{sub 3} compounds, while no detectable solubility was observed for the other binary compounds in the Ho–Ni–Ge system. Based on the magnetization measurements, the HoNi{sub 5}Ge{sub 3}, HoNi{sub 3}Ge{sub 2} and Ho{sub 3}Ni{sub 11}Ge{sub 4} (and isostructural (Tb, Dy){sub 3}Ni{sub 11}Ge{sub 4}) compounds have been found to show paramagnetic behavior down to 5 K, whereas Ho{sub 3}Ni{sub 2}Ge{sub 3} exhibits an antiferromagnetic transition at ~7 K. Additionally, the crystal structure of the new isostructural phases (Y, Yb)Ni{sub 3}Ge{sub 2} (ErNi{sub 3}Ge{sub 2}-type), Er{sub 3}Ni{sub 11}Ge{sub 4} (Sc{sub 3}Ni{sub 11}Ge{sub 4}-type) and (Y, Tb, Dy, Er, Tm){sub 3}Ni{sub 2}Ge{sub 3} (Hf{sub 3}Ni{sub 2}Si{sub 3}-type) has been also investigated. - Highlights: • Ho–Ni–Ge system has been investigated at 1070 K and up to ~60 at% Ho. • Eight known ternary holmium nickel germanides were confirmed in Ho–Ni–Ge. • Four new holmium nickel germanides were detected in Ho–Ni–Ge. • Eight new rare earth nickel germanides were detected in (Y, Tb, Dy, Er–Yb)–Ni–Ge. • HoNi{sub 5}Ge{sub 3}, HoNi{sub 3}Ge{sub 2},(Tb, Dy, Ho){sub 3}Ni{sub 11}Ge{sub 4} and Ho{sub 3}Ni{sub 2}Ge{sub 3} are paramagnet down to 5–7 K.« less

Reflections on the Gall-Peters Projection.

ERIC Educational Resources Information Center

Robinson, Arthur H.

1987-01-01

Explains the cartographic qualities of rectangular world maps and compares the merits of various projections such as the Mercator and the recently-created Gall-Peters. States that the Gall-Peters projection does not provide a reasonable base for a general world map; that no rectangular projection does. (JDH)

Remembering Peter Medway

ERIC Educational Resources Information Center

Hardcastle, John; Clements, Simon

2015-01-01

Peter Medway was an exceptionally able teacher, researcher and thinker, and his work throws light on governments, inspectors and educators. In the early 1960s, Peter met a theory which "established language as a major means of constructing our realities". Later, after teaching English in secondary schools for two decades, he reflected on…

Ripples from a Passing Ship: Memories; and a Legacy of Richard Peters

ERIC Educational Resources Information Center

Harris, Kevin

2013-01-01

This paper outlines aspects and dimensions of my "relationship" with Richard Peters from 1966 onward. The underlying suggestion is that, while Peters' contribution to philosophy of education was undeniably of major proportions, both that contribution and his legacy are institutional rather than substantive. (Contains 15 notes.)

77 FR 26538 - Vigue, Peter A.; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-04

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ID-6627-001] Vigue, Peter A.; Notice of Filing Take notice that on April 26, 2012, Peter A. Vigue submitted for filing, a supplement to the application for authority to hold interlocking positions filed on March 6, 2012, pursuant to...

77 FR 14773 - Vigue, Peter A.; Notice of Filing

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ID-6627-001] Vigue, Peter A.; Notice of Filing Take notice that on March 6, 2012, Peter A. Vigue submitted for filing, an application for authority to hold interlocking positions, pursuant to section 305(b) of the Federal Power Act, 16...

Short communication: Jersey × Holstein crossbreds compared with pure Holsteins for body weight, body condition score, fertility, and survival during the first three lactations.

PubMed

Heins, B J; Hansen, L B; Hazel, A R; Seykora, A J; Johnson, D G; Linn, J G

2012-07-01

Crossbred cows (n=80) resulting from the use of Jersey (JE) semen on their pure Holstein (HO) dams were compared with pure HO cows (n=77) for body weight, body condition score, fertility, and survival during their first 3 lactations. Cows were in 2 research herds of the University of Minnesota and calved from September 2003 to June 2008. The JE × HO crossbred cows had significantly less body weight during the first (-56 kg), second (-67 kg), and third (-82 kg) lactations than pure HO cows. However, JE × HO cows had significantly greater body condition score during the first (2.94 vs. 2.84), second (2.97 vs. 2.84), and third (2.99 vs. 2.87) lactations than pure HO cows. For fertility, JE × HO cows had fewer days to first breeding during the first (-10.6d), second (-8.4d), and third (-12.3d) lactations than pure HO cows. Crossbred cows were not significantly different from pure HO cows for number of services during first lactation; however, JE × HO cows had significantly fewer services (2.2) than pure HO cows (2.7) during the second lactation. Also, JE × HO cows had significantly fewer days open than pure HO cows in the first (-24 d), second (-42 d), and third (-42 d) lactations. For survival, JE × HO cows were not significantly different from pure HO cows for percentage of cows calving a second time; however, a tendency existed for a higher percentage of JE × HO cows (63.8%) than pure HO cows (49.4%) to calve a third time, and a higher percentage of JE × HO cows calved a third time within 28, 34, and 40 mo of first calving than pure HO cows. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Spectroscopy and microchip laser operation of Tm, Ho:KYW crystals with different Ho concentrations

NASA Astrophysics Data System (ADS)

Gusakova, N. V.; Kurilchik, S. V.; Yasukevich, A. S.; Kisel, V. E.; Dashkevich, V. I.; Orlovich, V. A.; Pavlyuk, A. A.; Vatnik, S. M.; Bagaev, S. N.; Kuleshov, N. V.

2018-02-01

The spectroscopic properties of Tm, Ho:KYW crystals with different Ho concentrations were investigated. The diode-pumped microchip laser operation of Tm (5 at.%), Ho (0.5 at.%):KYW and Tm (5 at.%), Ho (1 at.%):KYW was demonstrated. The highest, to our knowledge, output power of 480 mW with slope efficiency of 31% for CW Tm (5 at.%), Ho (0.5 at.%):KYW microchip laser was obtained.

Whole exome sequence analysis of Peters anomaly

PubMed Central

Weh, Eric; Reis, Linda M.; Happ, Hannah C.; Levin, Alex V.; Wheeler, Patricia G.; David, Karen L.; Carney, Erin; Angle, Brad; Hauser, Natalie

2015-01-01

Peters anomaly is a rare form of anterior segment ocular dysgenesis, which can also be associated with additional systemic defects. At this time, the majority of cases of Peters anomaly lack a genetic diagnosis. We performed whole exome sequencing of 27 patients with syndromic or isolated Peters anomaly to search for pathogenic mutations in currently known ocular genes. Among the eight previously recognized Peters anomaly genes, we identified a de novo missense mutation in PAX6, c.155G>A, p.(Cys52Tyr), in one patient. Analysis of 691 additional genes currently associated with a different ocular phenotype identified a heterozygous splicing mutation c.1025+2T>A in TFAP2A, a de novo heterozygous nonsense mutation c.715C>T, p.(Gln239*) in HCCS, a hemizygous mutation c.385G>A, p.(Glu129Lys) in NDP, a hemizygous mutation c.3446C>T, p.(Pro1149Leu) in FLNA, and compound heterozygous mutations c.1422T>A, p.(Tyr474*) and c.2544G>A, p.(Met848Ile) in SLC4A11; all mutations, except for the FLNA and SLC4A11 c.2544G>A alleles, are novel. This is the frst study to use whole exome sequencing to discern the genetic etiology of a large cohort of patients with syndromic or isolated Peters anomaly. We report five new genes associated with this condition and suggest screening of TFAP2A and FLNA in patients with Peters anomaly and relevant syndromic features and HCCS, NDP and SLC4A11 in patients with isolated Peters anomaly. PMID:25182519

AN ENZYME LINKED IMMUNOSORBENT ASSAY FOR THE HO-1 ISOFORM OF HEME OXYGENASE

EPA Science Inventory

AN ENZYME LINKED IMMUNOSORBENT ASSAY FOR THE HO-1 ISOFORM OF HEME OXYGENASE

Heme oxygenase (HO) occurs in biological tissues as two major isoforms HO-1 and HO-2. HO-1 is inducible by many treatments, particularly oxidative stress-related conditions such as depletion of gl...

What You See Is Not What You Get

ERIC Educational Resources Information Center

White-McMahon, Meredith

2010-01-01

When upset, 15-year-old Peter overreacts, dumping verbal hostility on everyone, even those trying to help. Peter's attempt to see the principal--who was out of the office--led to an emotionally explosive crisis. In this life space crisis intervention (LSCI), staff calmly tried to help Peter clarify distorted reality. But patient questioning raised…

75 FR 63533 - Gulf & Ohio Railways Holding Co., Inc., H. Peter Claussen and Linda C. Claussen-Continuance in...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35414] Gulf & Ohio Railways Holding Co., Inc., H. Peter Claussen and Linda C. Claussen--Continuance in Control Exemption--Lancaster & Chester Railroad, LLC Gulf & Ohio Railways Holding Co., Inc. (G&O), H. Peter Claussen and Linda...

Ritual, Imitation and Education in R. S. Peters

ERIC Educational Resources Information Center

Warnick, Bryan R.

2009-01-01

This article reconstructs R. S. Peters' underlying theory of ritual in education, highlighting his proposed link between ritual and the imitation of teachers. Rituals set the stage for the imitation of teachers and they invite students to experience practices whose value is not easily discernable from the outside. For Peters, rituals facilitate…

78 FR 77673 - Proposed CERCLA Administrative Cost Recovery Settlement; Cadie Auto Salvage Site, Belvidere...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

... the proposed settlement may be obtained from Peter Felitti, Assoc. Regional Counsel, EPA, Office of... addressed to Peter Felitti, Assoc. Regional Counsel, EPA, Office of Regional Counsel, Region 5, 77 W. Jackson Blvd., mail code: C-14J, Chicago, Illinois 60604. FOR FURTHER INFORMATION CONTACT: Peter Felitti...

Density-functional study of the structures and properties of holmium-doped silicon clusters HoSi n (n = 3-9) and their anions.

PubMed

Hou, Liyuan; Yang, Jucai; Liu, Yuming

2017-04-01

The structures and properties of Ho-doped Si clusters, including their adiabatic electron affinities (AEAs), simulated photoelectron spectra (PESs), stabilities, magnetic moments, and charge-transfer characteristics, were systematically investigated using four density-functional methods. The results show that the double-hybrid functional (which includes an MP2 correlation component) can accurately predict the ground-state structure and properties of Ho-doped Si clusters. The ground-state structures of HoSi n (n = 3-9) are sextuplet electronic states. The structures of these Ho-doped Si clusters (aside from HoSi 7 ) are substitutional. The ground-state structures of HoSi n - are quintuplet electronic states. Their predicted AEAs are in excellent agreement with the experimental ones. The mean absolute error in the theoretical AEAs of HoSi n (n = 4-9) is only 0.04 eV. The simulated PESs for HoSi n - (n = 5-9) are in good agreement with the experimental PESs. Based on its simulated PES and theoretical AEA, we reassigned the experimental PES of HoSi 4 - and obtained an experimental AEA of 2.2 ± 0.1 eV. The dissociation energies of Ho from HoSi n and HoSi n - (n = 3-9) were evaluated to test the relative stabilities of the clusters. HOMO-LUMO gap analysis indicated that doping the Si clusters with the rare-earth metal atom significantly increases their photochemical reactivity. Natural population analysis showed that the magnetic moments of HoSi n (n = 3-9) and their anions derive mainly from the Ho atom. It was also found that the magnetic moments of Ho in the HoSi n clusters are larger than the magnetic moment of an isolated Ho atom.

EDITORIAL Proceedings of the XIV International Conference on Small-Angle Scattering, SAS-2009

NASA Astrophysics Data System (ADS)

Ungar, Goran; Heenan, Richard

2010-10-01

There are 52 papers in these Proceedings. The papers are divided into 10 thematic sections and a section for invited papers and reviews. The sections and the respective section editors are given below. Section Editor(s) Invited Papers and Reviews Peter Griffiths, Wim Bras, Rudolf Winter Beamlines and Instrumentation Elliot Gilbert, Wim Bras, Nigel Rhodes Theory, Data processing and Modelling Jan Skov Pedersen, Carlo Knupp Biological Systems and Membranes Richard Heenan, Cameron Neylon Ceramics, Glasses and Porous Materials Rudolf Winter Colloids and Solutions Peter Griffiths Hierarchical Structures and Fibres Steve Eichhorn, Karen Edler Metallic and Magnetic Systems Armin Hoell Polymers Patrick Fairclough Time resolved Diffraction, Kinetic and Dynamical Studies João Cabral, Christoph Rau We are grateful to all section editors and the many anonymous referees for their invaluable effort which made the publication of the Proceedings possible. The refereeing process was strict and thorough, some papers were rejected and most were improved. The resulting compendium gives a good overview of recent developments in small-angle X-ray and neutron scattering theory, application, methods of analysis and instrumentation. Thus it should be a useful source of reference for a number of years to come. The papers are a good reflection of the material presented at the meeting. Because of the general high quality of the articles, it was difficult to decide which to highlight and be fair to all contributors. The following in particular have caught the attention of the editors. Highlighted papers A statistical survey of publications reporting the application of SAXS and SANS by Aldo Craievich (paper 012003) is recommended reading for anyone needing convincing about the vibrancy of this scientific field and the ever expanding use of these techniques. Two aspects of coherent X-ray scattering, made available by the advent of the 3rd generation synchrotron sources, are discussed in the papers by Felisa Berenguer and the Diamond/UCL team (012004) and by Birgit Fischer and the DESY/Rostock team (012026). The former describe their effort to reconstruct the image of wet collagen tissue from the speckled pattern of a narrow transmitted beam and complement the results of imaging by scanning SAXS. Fischer et al. utilize the coherence of the X-ray beam in the photon correlation spectroscopy mode to determine the dynamic structure factor, from which the q-dependence of the relaxation times was determined for solutions of charged colloidal particles. The nature of particle motion was thus determined, i.e. ballistic at lower concentrations vs. restricted by 'caging' at higher concentrations. The use of scanning microbeam diffraction was also described in the paper by the group of Peter Fratzl (012031), who combined it with tilting the sample in order to obtain what is referred to as 3D SAXS. In this way the orientation distribution of crystallites in callus tissue during bone fracture healing can be explored. Naoto Yagi et al. (012024) used microbeam SAXS and WAXS to study dental enamel crystals in a caries lesion. Anomalous, or resonant, X-ray scattering at low angles (ASAXS) was employed by Guenter Goerigk and Norbert Mattern (Jülich/Dresden) (012022) to study phase separation in the ternary alloy Ni-Nb-Y. Experiments were performed near the K-absorption edges of the three elements and the authors describe how they determined quantitatively the chemical composition of the different separate phases as well as short-range concentration fluctuations during spinodal decomposition. For organic materials, where heavy atoms are not present, typically sulphur would be replaced by Se, so ASAXS could be performed near the Se K-edge. However, Masashi Handa et al. from the University of Tokyo report in paper 012006 a feasibility study of using sulphur itself as the label. They deal with the challenging task of using low-energy X-rays at the sulphur K-edge. Alexandra Vasilieva and teams from St Petersburg and Moscow describe in paper 012029 a study of a FCC/HCP photonic crystal with a unit cell of 650 nm using the DUBBLE beamline at ESRF, where the incident beam is focused with a compound Berilium lens to give divergence in the microradian range. Defects, correlation lengths, mosaic spread and twinning could be studied in a thin film. The use of grazing incidence small- and intermediate-angle X-ray scattering (GISAXS) was illustrated on several examples of complex liquid crystal phases and nanoparticle systems by Xiangbing Zeng and the team from Sheffield in paper 012032. Apart from the intrinsic interest in the structure of thin films of these materials, the close proximity of the surface imposes usually a very high degree of preferred orientation, facilitating structural analysis. From the papers describing the use of neutron scattering, we highlight the study by Léon van Heijkamp and the Delft group, paper 012016, which describes proof-of-principle experiments using spin-echo SANS (SESANS) for the study of D2O-labeled liposomes and their destruction with a view of providing a nondestructive technique for monitoring targeted drug delivery for the destruction of tumor tissue. This technique is based on monitoring the decay of spin polarization of scattered neutrons, and it can probe correlation lengths from nanometres to tens of microns. In paper 012002 Thomas Zemb discusses the various ways in which SAXS and SANS data can be combined to investigate microemulsions of surfactants lacking long-range order. Thus, for example, it is described how form and structure factors can be separated, or how the degree of connectivity can be determined between rod-like entities forming 'molten cubic' or 'sponge' phases. In the Theory, Data Processing and Modelling section we highlight two papers. Paper 012012, by Carlos Cabrillo and co-workers from Madrid, presents a real-space model for powder samples of relatively highly ordered colloidal particles based on the radial pair distance distribution function. The model takes account of different types of disorder, i.e. of both 1st ('thermal') and 2nd ('paracrystalline') kind, as well as finite size, stacking and orientational disorder. In paper 012014 Salvino Ciccariello works out the 3D correlation function of plane objects, specifically a triangle of a general shape. This paves the way to analysing morphologies that can be approximated by cylinders of different cross-sections. Papers 012051 (Polte et al.) and 012047 (Bras et al.) report the use of SAS in combination with X-ray spectroscopy. Ristic et al. describe a real-time study of crystal nucleation induced by ultrasound (012049), while Marianne Imperor-Clerc et al. present an investigation of lyotropic liquid crystals under shear (012052). In the Polymers section Geoff Mitchell describes modelling of SANS data on electrospun fibres (012042), while Cabral et al. describes a study of nanoparticle aggregation in bulk and thin polymer films (012046). Work on phospholipid membranes was reported by Spinozzi et al. and by Onai et al. in papers 012019 and 012018, respectively. The latter deals with the effect of osmotic pressure on model 'lipid rafts', these being considered as having an important role in the function of the mammalian cell membrane. Readers interested in biological systems will find a number of other interesting papers describing the use of either SAXS or SANS in the Biological Systems and Membranes section. A number of descriptions of recent designs of SAXS (synchrotron) and SANS beamlines, as well as detector developments can be found in the section on Beamlines and Instrumentation. Goran Ungar, Editor-in-Chief Richard Heenan, Deputy Editor-in-Chief

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor.

PubMed

Lalonde, R; Hayzoun, K; Selimi, F; Mariani, J; Strazielle, C

2003-11-01

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.

Jim Peters' collapse in the 1954 Vancouver Empire Games marathon.

PubMed

Noakes, Tim; Mekler, Jackie; Pedoe, Dan Tunstall

2008-08-01

On 7 August 1954, the world 42 km marathon record holder, Jim Peters, collapsed repeatedly during the final 385 metres of the British Empire and Commonwealth Games marathon held in Vancouver, Canada. It has been assumed that Peters collapsed from heatstroke because he ran too fast and did not drink during the race, which was held in windless, cloudless conditions with a dry-bulb temperature of 28 degrees C. Hospital records made available to us indicate that Peters might not have suffered from exertional heatstroke, which classically produces a rectal temperature > 42 degrees C, cerebral effects and, usually, a fatal outcome without vigorous active cooling. Although Peters was unconscious on admission to hospital approximately 60 minutes after he was removed from the race, his rectal temperature was 39.4 degrees C and he recovered fully, even though he was managed conservatively and not actively cooled. We propose that Peters' collapse was more likely due to a combination of hyperthermia-induced fatigue which caused him to stop running; exercise-associated postural hypotension as a result of a low peripheral vascular resistance immediately he stopped running; and combined cerebral effects of hyperthermia, hypertonic hypernatraemia associated with dehydration, and perhaps undiagnosed hypoglycaemia. But none of these conditions should cause prolonged unconsciousness, raising the possibility that Peters might have suffered from a transient encephalopathy, the exact nature of which is not understood.

Determination of hydroxylated polychlorinated biphenyls (HO-PCBs) in blood plasma by high-performance liquid chromatography-electrospray ionization-tandem quadrupole mass spectrometry.

PubMed

Letcher, R J; Li, H X; Chu, S G

2005-01-01

Hydroxylated metabolites of polychlorinated biphenyls (HO-PCBs) and pentachlorophenol (PCP) are halogenated phenolic compounds, and they are increasingly common as environmental contaminants mainly in the blood of wildlife and humans. A methodology based on high-performance liquid chromatography (reversed-phase)-electrospray (negative) ionization-tandem quadrupole mass spectrometry (LC-ESI(-)-MS-MS) in the select ion monitoring or multiple reaction monitoring modes was developed for HO-PCB and PCP determination in blood plasma and serum. Among 11 environmentally relevant HO-PCB congeners and PCP spiked to fetal calf serum, quantitative assessments, including matrix effects on ESI(-) suppression/ enhancement, showed process (recovery) efficiencies of 73% to 89% without internal standard (IS) correction, and 88% to 103% with IS correction, and method limits of quantification ranging from 1 to 50 pg/g (wet weight). Using the developed LC-ESI(-)-MS methodology in comparison with GC-MS and GC-ECD based approaches, similar results were found for HO-PCB identification and quantification in the plasma of polar bear (Ursus maritimus) from the Canadian arctic. LC-ESI(-)-MS identified four HO-PCB congeners [4'-HO-2,2',4,6,6'-pentachlorobiphenyl (4'-HO-CB104), 4-HO-2,3,3',4',5-pentachlorobiphenyl (4-HO-CB107), 4-HO-2,3,3',5,5',6-hexachlorobiphenyl (4-HO-CB165) and 3'-HO-2,2',3,4,4',5,5'-heptachlorobiphenyl (3'-HO-CB180)], and 14 additional tetra- to hepta-chlorinated HO-PCBs isomers in the polar bear plasma.

Apo A1 Mimetic Rescues the Diabetic Phenotype of HO-2 Knockout Mice via an Increase in HO-1 Adiponectin and LKBI Signaling Pathway

PubMed Central

Cao, Jian; Puri, Nitin; Sodhi, Komal; Bellner, Lars; Abraham, Nader G.; Kappas, Attallah

2012-01-01

Insulin resistance, with adipose tissue dysfunction, is one of the hallmarks of metabolic syndrome. We have reported a metabolic syndrome-like phenotype in heme oxygenase (HO)-2 knockout mice, which presented with concurrent HO-1 deficiency and were amenable to rescue by an EET analog. Apo A-I mimetic peptides, such as L-4F, have been shown to induce HO-1 expression and decrease oxidative stress and adiposity. In this study we aimed to characterize alleviatory effects of HO-1 induction (if any) on metabolic imbalance observed in HO-2 KO mice. In this regard, HO-2(−/−) mice were injected with 2 mg/kg/day L-4F, or vehicle, i.p., for 6 weeks. As before, compared to WT animals, the HO-2 null mice were obese, displayed insulin resistance, and had elevated blood pressure. These changes were accompanied by enhanced tissue (hepatic) oxidative stress along with attenuation of HO-1 expression and activity and reduced adiponectin, pAMPK, and LKB1 expression. Treatment with L-4F restored HO-1 expression and activity and increased adiponectin, LKB1, and pAMPK in the HO-2(−/−) mice. These alterations resulted in a decrease in blood pressure, insulin resistance, blood glucose, and adiposity. Taken together, our results show that a deficient HO-1 response, in a state with reduced HO-2 basal levels, is accompanied by disruption of metabolic homeostasis which is successfully restored by an HO-1 inducer. PMID:22577519

Science and Technology Community in Crisis

DTIC Science & Technology

2002-05-01

centralized, highly bureaucratic, support system that considers itself an end, a point noted in the management literature by Peter Drucker :48 “What...Review Quarterly, Spring 2000. 48 Drucker , Peter F., Management : Tasks, Responsibilities, Practices, Apr 1993. 43 regionalization of personnel...technical areas as information technology, biotechnology, nanotechnology, etc. Peter Drucker , the well-known management expert once commented: “In

The Existential Concern of the Humanities R. S. Peters' Justification of Liberal Education

ERIC Educational Resources Information Center

Cuypers, Stefaan E.

2018-01-01

Richard Stanley Peters was one of the founding fathers of analytic philosophy of education in the twentieth century. After reviewing Peters' disentanglement of the ambiguities of liberal education, I reconstruct his view on the status and the existential foundations of the humanities. What emerges from my reconstruction is an original…

Farewell to the Chairman - Marine Gen. Peter Pace

Science.gov Websites

oath of office from Marine Gen. Peter Pace, who retired after more than 40 years active duty military wife Lynne after giving the general his retirement certificate. Defense Dept. photo by Cherie A solutions, Marine Gen. Peter Pace said here today as he retired from the Marine Corps after more than 40

The Future of the Digital Library: An Interview with Tom Peters

ERIC Educational Resources Information Center

Morrison, James L.; Peters, Tom

2005-01-01

This article presents an interview with Tom Peters, an academic librarian and founder of TAP Information Services, a firm that provides consulting services to libraries and other organizations in the information industry. Peters also serves as a consultant to LibraryCity, an ambitious project that seeks to make thousands of e-books in easy-to-use…

Otto Peters on Distance Education: The Industrialization of Teaching and Learning. Routledge Studies in Distance Education.

ERIC Educational Resources Information Center

Keegan, Desmond, Ed.

This book contains new and previously published translations of 11 essays and articles about the industrialization of teaching and learning in distance education that were originally published in German by Otto Peters between 1965 and 1993. A "Preface" (Desmond Keegan) and an introduction placing Peters' writings in their historical…

R. S. Peters' Normative Conception of Education and Educational Aims

ERIC Educational Resources Information Center

Katz, Michael S.

2009-01-01

This article aims to highlight why R. S. Peters' conceptual analysis of "education" was such an important contribution to the normative field of philosophy of education. In the article, I do the following: 1) explicate Peters' conception of philosophy of education as a field of philosophy and explain his approach to the philosophical analysis of…

Recognizing and Nurturing Hidden Creative Potential

ERIC Educational Resources Information Center

Connell, Elizabeth E.

2010-01-01

Peter, 7 years old, spends most of his time playing with his stick alone. After several unsuccessful attempts to get Peter to join his cousins, his aunt asks the boy's parents if they have considered having him evaluated by a psychologist. Peter's parents are not as concerned about the stick behavior as is his aunt. Although the attachment to his…

77 FR 3475 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-24

... Hennepin Avenue, Minneapolis, Minnesota 55480-0291: 1. Samuel B. Gault, Saint Peter, Minnesota, and Lisa R. Gault, Chaska, Minnesota, each to acquire 25 percent or more of the shares of Saint Peter Agency, Inc., Saint Peter, Minnesota, and thereby indirectly acquire control of The Nicollet County Bank of Saint...

The "Physically Educated" Person: Physical Education in the Philosophy of Reid, Peters and Aristotle

ERIC Educational Resources Information Center

MacAllister, James

2013-01-01

This article will derive a definition and account of the physically educated person, through an examination of the philosophy of Andrew Reid, Richard Peters and Aristotle. Initially, Reid's interpretation of Peters' views about the educational significance of practical knowledge (and physical education) will be considered. While it will…

Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice

PubMed Central

Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B.; Carter, A. Brent; Rowe, Steven M.; Matalon, Sadis; Thannickal, Victor J.; Agarwal, Anupam

2015-01-01

Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1+/+, HO-1−/−, and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1−/− mice exhibited more severe emphysema compared with HO-1+/+ or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1+/+, HO-1−/−, and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1−/− PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1+/+ PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. PMID:26071551

Heme oxygenase-1-mediated autophagy protects against pulmonary endothelial cell death and development of emphysema in cadmium-treated mice.

PubMed

Surolia, Ranu; Karki, Suman; Kim, Hyunki; Yu, Zhihong; Kulkarni, Tejaswini; Mirov, Sergey B; Carter, A Brent; Rowe, Steven M; Matalon, Sadis; Thannickal, Victor J; Agarwal, Anupam; Antony, Veena B

2015-08-01

Pulmonary exposure to cadmium, a major component of cigarette smoke, has a dramatic impact on lung function and the development of emphysema. Cigarette smoke exposure induces heme oxygenase-1 (HO-1), a cytoprotective enzyme. In this study, we employed a truncated mouse model of emphysema by intratracheal instillation of cadmium (CdCl2) solution (0.025% per 1 mg/kg body wt) in HO-1(+/+), HO-1(-/-), and overexpressing humanized HO-1 bacterial artificial chromosome (hHO-1BAC) mice. We evaluated the role of HO-1 in cadmium-induced emphysema in mice by analyzing histopathology, micro-computed tomography scans, and lung function tests. CdCl2-exposed HO-1(-/-) mice exhibited more severe emphysema compared with HO-1(+/+) or hHO-1BAC mice. Loss of pulmonary endothelial cells (PECs) from the alveolar capillary membrane is recognized to be a target in emphysema. PECs from HO-1(+/+), HO-1(-/-), and hHO-1BAC were employed to define the underlying molecular mechanism for the protection from emphysema by HO-1. Electron microscopy, expression of autophagic markers (microtubule-associated protein 1B-light chain 3 II, autophagy protein 5, and Beclin1) and apoptotic marker (cleaved caspase 3) suggested induction of autophagy and apoptosis in PECs after CdCl2 treatment. CdCl2-treated HO-1(-/-) PECs exhibited downregulation of autophagic markers and significantly increased cleaved caspase 3 expression and activity (∼4-fold higher). Moreover, hHO-1BAC PECs demonstrated upregulated autophagy and absence of cleaved caspase 3 expression or activity. Pretreatment of HO-1(+/+) PECs with rapamycin induced autophagy and resulted in reduced cell death upon cadmium treatment. Induction of autophagy following CdCl2 treatment was found to be protective from apoptotic cell death. HO-1 induced protective autophagy in PECs and mitigated cadmium-induced emphysema. Copyright © 2015 the American Physiological Society.

Isolation of 163Ho from dysprosium target material by HPLC for neutrino mass measurements

DOE PAGES

Mocko, Veronika; Taylor, Wayne  A.; Nortier, Francois M.; ...

2015-04-29

The rare earth isotope 163Ho is of interest for neutrino mass measurements. This report describes the isolation of 163Ho from a proton-irradiated dysprosium target and its purification. A Dy metal target was irradiated with 16 MeV protons for 10 h. After target dissolution, 163Ho was separated from the bulk Dy via cation-exchange high performance liquid chromatography using 70 mmol dm –3 α-hydroxyisobutyric acid as the mobile phase. Subsequent purification of the collected Ho fraction was performed to remove the α-hydroxyisobutyrate chelating agent and to concentrate the Ho in a low ionic strength aqueous matrix. The final solution was characterized bymore » MC-ICP-MS to determine the 163Ho/ 165Ho ratio, 163Ho and the residual Dy content. The HPLC purification process resulted in a decontamination factor 1.4E5 for Dy. As a result, the isolated Ho fraction contained 24.8 ±1.3 ng of 163Ho corresponding to holmium recovery of 72 ± 3%.« less

Isolation of 163Ho from dysprosium target material by HPLC for neutrino mass measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mocko, Veronika; Taylor, Wayne  A.; Nortier, Francois M.

The rare earth isotope 163Ho is of interest for neutrino mass measurements. This report describes the isolation of 163Ho from a proton-irradiated dysprosium target and its purification. A Dy metal target was irradiated with 16 MeV protons for 10 h. After target dissolution, 163Ho was separated from the bulk Dy via cation-exchange high performance liquid chromatography using 70 mmol dm –3 α-hydroxyisobutyric acid as the mobile phase. Subsequent purification of the collected Ho fraction was performed to remove the α-hydroxyisobutyrate chelating agent and to concentrate the Ho in a low ionic strength aqueous matrix. The final solution was characterized bymore » MC-ICP-MS to determine the 163Ho/ 165Ho ratio, 163Ho and the residual Dy content. The HPLC purification process resulted in a decontamination factor 1.4E5 for Dy. As a result, the isolated Ho fraction contained 24.8 ±1.3 ng of 163Ho corresponding to holmium recovery of 72 ± 3%.« less

Adenoviral transfer of the heme oxygenase-1 gene protects striatal astrocytes from heme-mediated oxidative injury.

PubMed

Teng, Zhi-Ping; Chen, Jing; Chau, Lee-Young; Galunic, Nicholas; Regan, Raymond F

2004-11-01

Heme oxygenase-1 (HO-1) is induced in the CNS after hemorrhage, and may have an effect on injury to surrounding tissue. Hemin, the preferred substrate of HO, is a neurotoxin that is present in intracranial hematomas. In a prior study, we observed that HO inhibitors increased the vulnerability of cultured cortical astrocytes to heme-mediated oxidative injury. To investigate the effect of HO more specifically, we used an adenoviral vector encoding the human HO-1 gene to specifically increase HO-1 expression. Incubation with 100 MOI of the HO-1 adenovirus (Adv-HHO-1) for 24 h increased both HO-1 protein and HO activity; a control adenovirus lacking the HO-1 gene had no effect. Using a DNA probe that was specific for human HO-1, 80.5 +/- 7.2% of astrocytes were observed to be infected by in situ hybridization. The cell death produced by 30-60 microM hemin was significantly reduced by pretreatment with 100 MOI Adv-HHO-1, as assessed by LDH release, propidium iodide exclusion, and MTT reduction assay. The threefold increase in cell protein oxidation produced by hemin was also attenuated in cultures pretreated with Adv-HHO-1. These results support the hypothesis that HO-1 protects astrocytes from heme-mediated oxidative injury. Specifically increasing astrocytic HO-1 by gene transfer may have a beneficial effect on hemorrhagic CNS injury.

Peroxy radical measurements with NCAR's chemical amplifier

NASA Technical Reports Server (NTRS)

Cantrell, Christopher; Shetter, Richard; Calvert, Jack G.

1994-01-01

The present NCAR instrument for HO2/RO2 measurements has been described previously. It is based on the reactions involving HO2, RO2, and HO radicals with CO and NO. Since (HO2) + (RO2) + (HO) is much greater than (HO) for most atmospheres, it is useful as a peroxy radical detector. Operation of the instrument depends on the creation of a chemical chain reaction which is initiated as HO2 and RO2 radicals in ambient air encounter added NO gas; this forms an NO2 molecule and an HO or RO radical: HO2(RO2) + NO yields HO(RO) + NO2. RO radicals react relatively efficiently with O2 to form an HO2 radical, and subsequently an HO-radical, by reaction with NO. CO gas added to the reaction chamber during part of the operating cycle, recycles the HO to HO2; HO + CO (+O2) yields HO2 + CO2. The reaction sequence may form several hundred NO2 molecules per HO2 (RO2) originally present, before chain termination occurs. The added CO is replaced by N2 addition periodically so that the chain reaction is suppressed, and a 'blank' signal resulting from NO2, O3 and possibly other NO2-forming species (non-chain processes) in ambient air is recorded. The difference between the signal with and without CO is proportional to the peroxy radical concentration. The NO2 produced is monitored using a sensitive luminol chemiluminescence detector system. In the NCAR instrument the length of the amplification chain is determined using a stable source of HO2 radicals (H2O2 thermal decomposition); the ratio of the signal seen with CO present to that with N2 present gives the sensitivity of the instrument to HO2 (molecules of NO2 formed/peroxy radical). The instrument is automated to carry out in hourly repeated cycles: (1) chain length determination; (2) NO2 calibration; and (3) linearity check on the response of signals. One minute averages of signals are normally recorded. The sensitivity of the instrument to detect peroxy radicals is in the pptv range. The present instrument has operated continuously (24 hr/day) in the field studies which extended over a period of several weeks. The major advantages of this instrument are as follows: (1) its relative simplicity; (2) low power requirements; and (3) its rapid response to all types of peroxy radicals--HO2, CH3O2 and the higher alkyl and acyl peroxy radicals; however not all RO2 species generate HO2 radicals with perfect efficiency and hence have somewhat lower response/molecule than HO2 radicals.

Characterisation of Anopheles gambiae heme oxygenase and metalloporphyrin feeding suggests a potential role in reproduction.

PubMed

Spencer, Christopher S; Yunta, Cristina; de Lima, Glauber Pacelli Gomes; Hemmings, Kay; Lian, Lu-Yun; Lycett, Gareth; Paine, Mark J I

2018-05-03

The mosquito Anopheles gambiae is the principal vector for malaria in sub-Saharan Africa. The ability of A. gambiae to transmit malaria is strictly related to blood feeding and digestion, which releases nutrients for oogenesis, as well as substantial amounts of highly toxic free heme. Heme degradation by heme oxygenase (HO) is a common protective mechanism, and a gene for HO exists in the An. gambiae genome HO (AgHO), although it has yet to be functionally examined. Here, we have cloned and expressed An. gambiae HO (AgHO) in E. coli. Purified recombinant AgHO bound hemin stoichiometrically to form a hemin-enzyme complex similar to other HOs, with a K D of 3.9 ± 0.6 μM; comparable to mammalian and bacterial HOs, but 7-fold lower than that of Drosophila melanogaster HO. AgHO also degraded hemin to biliverdin and released CO and iron in the presence of NADPH cytochrome P450 oxidoreductase (CPR). Optimal AgHO activity was observed at 27.5 °C and pH 7.5. To investigate effects of AgHO inhibition, adult female A. gambiae were fed heme analogues Sn- and Zn-protoporphyrins (SnPP and ZnPP), known to inhibit HO. These led to a dose dependent decrease in oviposition. Cu-protoporphyrin (CuPP), which does not inhibit HO had no effect. These results demonstrate that AgHO is a catalytically active HO and that it may play a key role in egg production in mosquitoes. It also presents a potential target for the development of compounds aimed at sterilising mosquitoes for vector control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Efficient upconversion emission in Ho3+/Nd3+ co-doped oxyfluorosilicate glasses

NASA Astrophysics Data System (ADS)

Devarajulu, G.; Raju, B. Deva Prasad

2018-04-01

We report on an efficient Ho3+ and Ho3+/Nd3+ co-doped oxyfluorosilicate glasses upon excitation with an 808 nm laser diode. The detailed fluorescence have been studied under this excitation source and energy transfer mechanisms in Ho3+/Nd3+ co-doped oxyfluorosilicate glasses. The upconversion peaks at 486, 547 and 596 nm were observed in Nd3+/Ho3+ co-doped sample. The intensity of upconversion emission transitions in Ho3+ depends on the neodymium codopent concentration. These results indicate that Nd3+ ions can be potentially used as sensitizer for Ho3+ ions to stimulate the intense upconversion emission. The energy transfer mechanism between Nd3+ and Ho3+ was analyzed pursuant to the absorption spectra, upconversion spectra and the energy level structures of Nd3+ and Ho3+ ions have been briefly discussed.

Interview with Peter McLaren, on His Work, on His Visit to Turkey and on Ongoing Popular Struggles

ERIC Educational Resources Information Center

Fassbinder, Samuel Day

2013-01-01

Peter McLaren is, as the back cover of his (2005) Capitalists & Conquerors: a critical pedagogy against empire says, "professor of urban education at the Graduate School of Education and Information Studies at the University of California, Los Angeles". Peter is also now a Distinguished Fellow in Critical Studies at Chapman…

Against the Corporate Culture Ideology: An Interview with Peter Mayo

ERIC Educational Resources Information Center

Suoranta, Juha

2010-01-01

This article presents an interview with Peter Mayo, author and expert in the field of sociology of adult education, on his major influences in this area, his books, and his views on the role of radical adult education and radical scholarship in the future. In the interview, Peter Mayo states that his initial view of adult education was quite a…

20 CFR 416.1166 - How we deem income to you and your eligible child from your ineligible spouse.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... Example 1. Mary, a blind individual, lives with her husband, John, and their disabled child, Peter. Mary and Peter have no income, but John is employed and earns $605 per month. We determine Mary's... is eligible; therefore, there is no income to be deemed to Peter. Example 2. Al, a disabled...

Report on Teaching: Analysis of Some of the Most Notable Improvements in Amesican Undergraduate Teaching. No. 4.

ERIC Educational Resources Information Center

Change Magazine, 1977

1977-01-01

The fourth in a series of reports on undergraduate teaching contains articles on three disciplines: (1) geography (William D. Pattison, Salvatore J. Natoli, Peter Binzen, Charles J. Sugnet, Edwin Kiester, Jr., Sally Valente Kiester, Evan Jenkins, Peter Kakela, David Lanegran, Paul W. English, Peter Gould, and Alan DeLucia); (2) music (Theodore A.…

Fertility, survival, and conformation of Montbéliarde × Holstein and Viking Red × Holstein crossbred cows compared with pure Holstein cows during first lactation in 8 commercial dairy herds.

PubMed

Hazel, A R; Heins, B J; Hansen, L B

2017-11-01

Montbéliarde (MO) × Holstein (HO) and Viking Red (VR) × HO crossbred cows were compared with pure HO cows in 8 large, high-performance dairy herds in Minnesota. All cows calved for the first time from December 2010 to April 2014. Fertility and survival traits were calculated from records of insemination, pregnancy diagnosis, calving, and disposal that were recorded via management software. Body condition score and conformation were subjectively scored once during early lactation by trained evaluators. The analysis of survival to 60 d in milk included 536 MO × HO, 560 VR × HO, and 1,033 HO cows during first lactation. Cows analyzed for other fertility, survival, and conformation traits had up to 13% fewer cows available for analysis. The first service conception rate of the crossbred cows (both types combined) increased 7%, as did the conception rate across the first 5 inseminations, compared with the HO cows during first lactation. Furthermore, the combined crossbred cows (2.11 ± 0.05) had fewer times bred than HO cows (2.30 ± 0.05) and 10 fewer d open compared with their HO herdmates. Across the 8 herds, breed groups did not differ for survival to 60 d in milk; however, the superior fertility of the crossbred cows allowed an increased proportion of the combined crossbreds (71 ± 1.5%) to calve a second time within 14 mo compared with the HO cows (63 ± 1.5%). For survival to second calving, the combined crossbred cows had 4% superior survival compared with the HO cows. The MO × HO and VR × HO crossbred cows both had increased body condition score (+0.50 ± 0.02 and +0.25 ± 0.02, respectively) but shorter stature and less body depth than HO cows. The MO × HO cows had less set to the hock and a steeper foot angle than the HO cows, and the VR × HO cows had more set to the hock with a similar foot angle to the HO cows. The combined crossbred cows had less udder clearance from the hock than HO cows, more width between both front and rear teats, and longer teat length than the HO cows; however, the frequency of first-lactation cows culled for udder conformation was uniformly low (<1%) across the breed groups. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effect of heme oxygenase-1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro.

PubMed

Cao, Yi; Wu, Ben-Juan; Zheng, Wei-Ping; Yin, Ming-Li; Liu, Tao; Song, Hong-Li

2017-07-01

In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-α (TNF-α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO + MSCs or HO-MSCs. mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1 and the release of cytokines were measured. ZO-1 and human HO-1 in Caco2 were significantly decreased after treatment with TNF-α; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO-1 was not significantly affected by Caco2 treatment with TNF-α, Ad-HO, and MSCs. In contrast, ZO-1 and human HO-1 increased significantly when the damaged Caco2 was treated with HO-MSCs. HO-MSCs showed the strongest effect on the expression of ZO-1 in colon epithelial cells. Coculture with HO-MSCs showed the most significant effects on reducing the expression of IL-2, IL-6, IFN-γ and increasing the expression of IL-10. HO-MSCs protected the intestinal epithelial barrier, in which endogenous HO-1 was involved. HO-MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti-inflammatory factors. These results suggested that HO-MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO-1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases. © 2017 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

Survival, lifetime production, and profitability of Normande × Holstein, Montbéliarde × Holstein, and Scandinavian Red × Holstein crossbreds versus pure Holsteins.

PubMed

Heins, B J; Hansen, L B; De Vries, A

2012-02-01

Pure Holstein (HO) cows (n=416) were compared with Normande (NO) × HO (n=251), Montbéliarde (MO) × HO (n=503), and Scandinavian Red (SR) × HO (n=321) crossbred cows for survival, lifetime production, and profitability in 6 commercial herds in California. The SR crossbred cows were sired by both Swedish Red and Norwegian Red bulls. Cows calved from June 2002 to January 2009. For analysis of survival to subsequent calvings, lifetime production, and profitability, data were restricted to 3 of 6 herds because they had at least 20 cows in each of the breed groups. All cows had the opportunity to calve at least 4 times. Best prediction, which is used by USDA for national genetic evaluations in the United States, was used to determine lifetime production to 4 yr (1,461 d) in the herd after first calving from test-day observations. Production and survival were estimated after 4 yr to calculate lifetime profit. A profit function was defined to include revenues and expenses for milk, fat, protein, and other solids production; somatic cell count; reproduction; feed intake; calf value; salvage value; dead cow disposal; and fixed cost. The NO × HO (1.2%), MO × HO (2.0%), and SR × HO cows (1.6%) had significantly fewer deaths than did pure HO cows (5.3%) during the first 305 d of first lactation. All crossbred groups had significantly more cows that calved a second, third, and fourth time, and had mean survival that was 300 to 400 d longer than did pure HO cows. The NO × HO, MO × HO, and SR × HO cows had significantly higher lifetime fat plus protein production than did pure HO cows up to 1,461 d after first calving. For profitability (ignoring possible differences in health costs), NO × HO cows had 26% greater projected lifetime profit per cow, but 6.7% less profit per cow-day, than did pure HO cows. On the other hand, MO × HO and SR × HO cows had 50 to 44%, respectively, more projected lifetime profit per cow and 5.3 to 3.6%, respectively, more projected profit per cow-day than did pure HO cows. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Quantitative Voxel-to-Voxel Comparison of TriBeam and DCT Strontium Titanate Three-Dimensional Data Sets (Postprint)

DTIC Science & Technology

2015-02-09

Peter Gumbsch Karlsruhe Institute of Technology Melanie Syha European Synchrotron Radiation Facility Peter Gumbsch Fraunhofer IWM 9...REPORT DOCUMENTATION PAGE Cont’d 6. AUTHOR(S) 3) Melanie Syha - ESRF 4) Peter Gumbsch - Fraunhofer IWM 7. PERFORMING ORGANIZATION NAME(S...4) Fraunhofer IWM , Woelerstr. 11, 79108 Freiburg, Germany Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std

Theories of Power, Poverty, and Law: In Commemoration of the Contributions of Peter Bachrach--The Challenge of Peter Bachrach

ERIC Educational Resources Information Center

Lukes, Steven

2010-01-01

Peter Bachrach had a remarkable impact on those who encountered him in person and on generations of readers. Judith Baer vividly captures, among other things, his inspiring, emboldening influence on his students and the sheer fun it was to be with him. My recollections are of exciting, forward moving, intense, and probing arguments, in private and…

Is R. S. Peters' Way of Mentioning Women in His Texts Detrimental to Philosophy of Education? Some Considerations and Questions

ERIC Educational Resources Information Center

Lees, Helen E.

2012-01-01

Discussion in this article considers the unfortunate way R.S. Peters made mention of women when it was pertinent to his argumentation: portraying them, directly or indirectly, as abuse-able (murderable), deficient, aberrant, clueless and inconstant. It is argued that the high profile and esteem within which Peter's texts are held within philosophy…

Reflections on Peters' View of the Nature and Purpose of Work in Philosophy of Education

ERIC Educational Resources Information Center

Aspin, D. N.

2013-01-01

In this article I describe the analytic approach adopted by Peters, his colleagues and followers of the "London line" in the 1960s and 1970s and argue that, even in those times, other approaches to philosophy of education were being valued and practised. I show that Peters and his colleagues later became aware of the need for philosophy of…

Heme Oxygenase-1 Promotes Survival of Renal Cancer Cells through Modulation of Apoptosis- and Autophagy-regulating Molecules*

PubMed Central

Banerjee, Pallavi; Basu, Aninda; Wegiel, Barbara; Otterbein, Leo E.; Mizumura, Kenji; Gasser, Martin; Waaga-Gasser, Ana Maria; Choi, Augustine M.; Pal, Soumitro

2012-01-01

The cytoprotective enzyme heme oxygenase-1 (HO-1) is often overexpressed in different types of cancers and promotes cancer progression. We have recently shown that the Ras-Raf-ERK pathway induces HO-1 to promote survival of renal cancer cells. Here, we examined the possible mechanisms underlying HO-1-mediated cell survival. Considering the growing evidence about the significance of apoptosis and autophagy in cancer, we tried to investigate how HO-1 controls these events to regulate survival of cancer cells. Rapamycin (RAPA) and sorafenib, two commonly used drugs for renal cancer treatment, were found to induce HO-1 expression in renal cancer cells Caki-1 and 786-O; and the apoptotic effect of these drugs was markedly enhanced upon HO-1 knockdown. Overexpression of HO-1 protected the cells from RAPA- and sorafenib-induced apoptosis and also averted drug-mediated inhibition of cell proliferation. HO-1 induced the expression of anti-apoptotic Bcl-xL and decreased the expression of autophagic proteins Beclin-1 and LC3B-II; while knockdown of HO-1 down-regulated Bcl-xL and markedly increased LC3B-II. Moreover, HO-1 promoted the association of Beclin-1 with Bcl-xL and Rubicon, a novel negative regulator of autophagy. Drug-induced dissociation of Beclin-1 from Rubicon and the induction of autophagy were also inhibited by HO-1. Together, our data signify that HO-1 is up-regulated in renal cancer cells as a survival strategy against chemotherapeutic drugs and promotes growth of tumor cells by inhibiting both apoptosis and autophagy. Thus, application of chemotherapeutic drugs along with HO-1 inhibitor may elevate therapeutic efficiency by reducing the cytoprotective effects of HO-1 and by simultaneous induction of both apoptosis and autophagy. PMID:22843690

Structure prediction and activity analysis of human heme oxygenase-1 and its mutant.

PubMed

Xia, Zhen-Wei; Zhou, Wen-Pu; Cui, Wen-Jun; Zhang, Xue-Hong; Shen, Qing-Xiang; Li, Yun-Zhu; Yu, Shan-Chang

2004-08-15

To predict wild human heme oxygenase-1 (whHO-1) and hHO-1 His25Ala mutant (delta hHO-1) structures, to clone and express them and analyze their activities. Swiss-PdbViewer and Antheprot 5.0 were used for the prediction of structure diversity and physical-chemical changes between wild and mutant hHO-1. hHO-1 His25Ala mutant cDNA was constructed by site-directed mutagenesis in two plasmids of E. coli DH5alpha. Expression products were purified by ammonium sulphate precipitation and Q-Sepharose Fast Flow column chromatography, and their activities were measured. rHO-1 had the structure of a helical fold with the heme sandwiched between heme-heme oxygenase-1 helices. Bond angle, dihedral angle and chemical bond in the active pocket changed after Ala25 was replaced by His25, but Ala25 was still contacting the surface and the electrostatic potential of the active pocket was negative. The mutated enzyme kept binding activity to heme. Two vectors pBHO-1 and pBHO-1(M) were constructed and expressed. Ammonium sulphate precipitation and column chromatography yielded 3.6-fold and 30-fold higher purities of whHO-1, respectively. The activity of delta hHO-1 was reduced 91.21% after mutation compared with whHO-1. Proximal His25 ligand is crucial for normal hHO-1 catalytic activity. delta hHO-1 is deactivated by mutation but keeps the same binding site as whHO-1. delta hHO-1 might be a potential inhibitor of whHO-1 for preventing neonatal hyperbilirubinemia.

Structure prediction and activity analysis of human heme oxygenase-1 and its mutant

PubMed Central

Xia, Zhen-Wei; Zhou, Wen-Pu; Cui, Wen-Jun; Zhang, Xue-Hong; Shen, Qing-Xiang; Li, Yun-Zhu; Yu, Shan-Chang

2004-01-01

AIM: To predict wild human heme oxygenase-1 (whHO-1) and hHO-1 His25Ala mutant (△hHO-1) structures, to clone and express them and analyze their activities. METHODS: Swiss-PdbViewer and Antheprot 5.0 were used for the prediction of structure diversity and physical-chemical changes between wild and mutant hHO-1. hHO-1 His25Ala mutant cDNA was constructed by site-directed mutagenesis in two plasmids of E. coli DH5α . Expression products were purified by ammonium sulphate precipitation and Q-Sepharose Fast Flow column chromatography, and their activities were measured. RESULTS: rHO-1 had the structure of a helical fold with the heme sandwiched between heme-heme oxygenase-1 helices. Bond angle, dihedral angle and chemical bond in the active pocket changed after Ala25 was replaced by His25, but Ala25 was still contacting the surface and the electrostatic potential of the active pocket was negative. The mutated enzyme kept binding activity to heme. Two vectors pBHO-1 and pBHO-1(M) were constructed and expressed. Ammonium sulphate precipitation and column chromatography yielded 3.6-fold and 30-fold higher purities of whHO-1, respectively. The activity of △hHO-1 was reduced 91.21% after mutation compared with whHO-1. CONCLUSION: Proximal His25 ligand is crucial for normal hHO-1 catalytic activity. △hHO-1 is deactivated by mutation but keeps the same binding site as whHO-1. △hHO-1 might be a potential inhibitor of whHO-1 for preventing neonatal hyperbilirubinemia. PMID:15285018

Enhancement of DEN-induced liver tumorigenesis in heme oxygenase-1 G143H mutant transgenic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Jianfeng; Wang, Dayong; Xiao, Haifeng

Heme oxygenase (HO) is the rate-limiting enzyme in heme metabolism. HO-1 exhibits anti-oxidative and anti-inflammatory function via the actions of its metabolite, respectively. A growing body of evidence demonstrates that HO-1 is implicated in the pathogenesis and progression of several types of cancer. However, whether HO-1 takes part in healthy-premalignant-malignant transformation is still undefined. In this study, we took advantage of transgenic mice which over-expressed HO-1 dominant negative mutant (HO-1 G143H) and observed its susceptibility to DEN-induced hepatocarcinogenesis. Our results indicate that HO-1 G143H mutant accelerates the progression of tumorigenesis and tumor growth. The mechanism is closely related to enhancementmore » of ROS production which induce more hepatocytes death and secretion of inflammatory cytokines, proliferation of surviving hepatocytes. Our result provides the direct evidence that HO-1 plays an important protective role in liver carcinogenesis. Alternatively, we suggest the possible explanation on effect of HO-1 promoter polymorphism which involved in tumorigenesis. - Highlights: • Enhancement of DEN-induced hepatocarcinogenesis in HO-1 G143H Tg mice. • HO-1G143H mutant enhanced DEN-induced ROS production and liver injury. • HO-1G143H mutant aggravated DEN-induced changes of inflammatory factors and cell proliferation.« less

Silencing heme oxygenase-1 gene expression in retinal pigment epithelial cells inhibits proliferation, migration and tube formation of cocultured endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Wenjie; Zhang, Xiaomei, E-mail: zhangxm667@163.com; Lu, Hong

2013-05-10

Highlights: •HO-1 is highly induced in RPE cells by hypoxia. •Inhibition of HO-1 activity and knockdown of HO-1 expression inhibit VEGF expression in RPE cells under hypoxia. •Knockdown of HO-1 in RPE cells inhibits angiogenesis of endothelial cells in vitro. -- Abstract: Heme oxygenase-1 (HO-1) plays an important role in the vasculature and in the angiogenesis of tumors, wounds and other environments. Retinal pigment epithelial (RPE) cells and choroidal endothelial cells (CECs) are the main cells involved in choroidal neovascularization (CNV), a process in which hypoxia plays an important role. Our aim was to evaluate the role of human RPE-cellmore » HO-1 in the angiogenic activities of cocultured endothelial cells under hypoxia. Small interfering RNA (siRNA) for HO-1 was transfected into human RPE cell line ARPE-19, and zinc protoporphyrin (ZnPP) was used to inhibit HO-1 activity. Knockdown of HO-1 expression and inhibition of HO-1 activity resulted in potent reduction of the expression of vascular endothelial growth factor (VEGF) under hypoxia. Furthermore, knockdown of HO-1 suppressed the proliferation, migration and tube formation of cocultured endothelial cells. These findings indicated that HO-1 might have an angiogenic effect in CNV through modulation of VEGF expression and might be a potential target for treating CNV.« less

Interpreting Bodies. Elena Castellani (ed.) Interpreting Bodies: Classical and Quantum Objects in Modern Physics (Princeton: Princeton University Press, 1998), viii+329 pp., ISBN 0-691-01725-5, paperback, 19.95 US, ISBN 0-691-01724-7, cloth, 65.00 US.

NASA Astrophysics Data System (ADS)

Ruetsche, Laura

The objects of the empirical science known as particle physics are not like objects ordinarily conceived. Physicists' particles can enter states strangely entangled with those of other particles; they can obey statistics which suggest that they lack genidentity; their properties (some think) are created in measurement, or (others think) can only be limned from the symmetries of the theory describing them. 'The implications of contemporary physical theories for the debate on the nature of objects' provides 'the central theme' (p. 4) of Interpreting Bodies, editor Elena Castellani's new collection of essays. Contributions to the volume vary dramatically in vintage (Born's and Reichenbach's are well into middle age; others appear here for the first time); in approach (the collection includes Giuliano Toraldo diFrancia's nine-page history of the object concept from Democritus to d'Espagnat, Peter Mittelstaedt's discussion of the Kantian constitution of quantum objects, and Giulo Peruzzi's explication of the scattering cross section and its role in experimental particle physics); and in intended audience. Lacking the space to treat each contribution in turn, I will focus on those dealing with the problem of the One and the Many.

AN ELISA ASSAY FOR HEME OXYGENASE (HO-1)

EPA Science Inventory

An ELISA assay for heme oxygenase (HO-l )

Abstract

A double antibody capture ELISA for the HO-l protein has been developed to separately quantitate HO-I protein. The use of 2.5% NP40 detergent greatly assists in freeing HO-l protein from membranes and/or other cel...

Production, Quality Control and Biological Evaluation of 166Ho-PDTMP as a Possible Bone Palliation Agent

PubMed Central

Zolghadri, Samaneh; Jalilian, Amir Reza; Naseri, Zohreh; Yousefnia, Hassan; Bahrami-Samani, Ali; Ghannadi-Maragheh, Mohammad; Afarideh, Hossein

2013-01-01

Objective(s): In this study, 166Ho-1,2-propylene di-amino tetra(methy1enephosphonicAcid) (166Ho-PDTMP) complex was prepared as a bone palliation agent. Materials and Methods: The complex was successfully prepared using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 n.cm-2.s-1) of natural Ho(NO3)3 samples followed by radiolabeling and stability studies. Biodistribution in wild type rats was also peformed. Results: The complex was prepared with the specific activity of 278 GBq/mg and high radiochemical purity (>99%, checked by ITLC). 166Ho-PDTMP complex was stabilized in the final preparation and in the presence of human serum (>90%) up to 72 hr. The biodistribution of 166Ho-PDTMP in wild-type rats demonstrated significant bone uptake was up to 48 hr compared to 166HoCl3. Conclusion: The produced 166Ho-PDTMP properties suggest a possible new bone palliative therapeutic to overcome the metastatic bone pains. PMID:23826495

Curcumin-induced heme oxygenase-1 expression prevents H2O2-induced cell death in wild type and heme oxygenase-2 knockout adipose-derived mesenchymal stem cells.

PubMed

Cremers, Niels A J; Lundvig, Ditte M S; van Dalen, Stephanie C M; Schelbergen, Rik F; van Lent, Peter L E M; Szarek, Walter A; Regan, Raymond F; Carels, Carine E; Wagener, Frank A D T G

2014-10-08

Mesenchymal stem cell (MSC) administration is a promising adjuvant therapy to treat tissue injury. However, MSC survival after administration is often hampered by oxidative stress at the site of injury. Heme oxygenase (HO) generates the cytoprotective effector molecules biliverdin/bilirubin, carbon monoxide (CO) and iron/ferritin by breaking down heme. Since HO-activity mediates anti-apoptotic, anti-inflammatory, and anti-oxidative effects, we hypothesized that modulation of the HO-system affects MSC survival. Adipose-derived MSCs (ASCs) from wild type (WT) and HO-2 knockout (KO) mice were isolated and characterized with respect to ASC marker expression. In order to analyze potential modulatory effects of the HO-system on ASC survival, WT and HO-2 KO ASCs were pre-treated with HO-activity modulators, or downstream effector molecules biliverdin, bilirubin, and CO before co-exposure of ASCs to a toxic dose of H2O2. Surprisingly, sensitivity to H2O2-mediated cell death was similar in WT and HO-2 KO ASCs. However, pre-induction of HO-1 expression using curcumin increased ASC survival after H2O2 exposure in both WT and HO-2 KO ASCs. Simultaneous inhibition of HO-activity resulted in loss of curcumin-mediated protection. Co-treatment with glutathione precursor N-Acetylcysteine promoted ASC survival. However, co-incubation with HO-effector molecules bilirubin and biliverdin did not rescue from H2O2-mediated cell death, whereas co-exposure to CO-releasing molecules-2 (CORM-2) significantly increased cell survival, independently from HO-2 expression. Summarizing, our results show that curcumin protects via an HO-1 dependent mechanism against H2O2-mediated apoptosis, and likely through the generation of CO. HO-1 pre-induction or administration of CORMs may thus form an attractive strategy to improve MSC therapy.

Areal lithologic changes in bedrock aquifers in southeastern Minnesota as determined from natural-gamma borehole logs methods

USGS Publications Warehouse

Woodward, D.G.

1984-01-01

Interpretation of natural-gamma logs indicates that the shaley and silty sandstones that comprise the basal St. Peter confining bed, which separates the St. Peter and Prairie du Chien aquifers, are as much as 80 feet thick in the Twin City basin, but are absent in the southern part of the embayment. Differences in potentiometric head across the basal St. Peter are about 30 feet in the Twin City basin where the confining bed is present but only 5 to 10 feet to the south where the confining bed is absent and where the St. Peter aquifer directly overlies the Prairie du Chien-Jordan aquifer.

Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

PubMed

Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

2003-01-01

Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

Measurement of HO2 chemical kinetics with a new detection method

NASA Technical Reports Server (NTRS)

Lee, Long C.; Suto, Masako

1986-01-01

Reaction rate constants of HO2+O3 were measured at various temperatures using a newly developed HO2 detection method. HO2 was detected by the OH(A-X) emission produced from photodissociative excitation of HO2 at 147 nm. In order to examine the possible interference of other emitting species with the HO2 detection, the photoexcitation processes of all the chemical species existing in the discharge flow tube were also investigated. The results are summarized.

Skin Barrier Restoration and Moisturization Using Horse Oil-Loaded Dissolving Microneedle Patches.

PubMed

Lee, Chisong; Eom, Younghyon Andrew; Yang, Huisuk; Jang, Mingyu; Jung, Sang Uk; Park, Ye Oak; Lee, Si Eun; Jung, Hyungil

2018-01-01

Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization. © 2018 S. Karger AG, Basel.

Paracrine action of HO-1-modified mesenchymal stem cells mediates cardiac protection and functional improvement.

PubMed

Zeng, Bin; Ren, Xiaofeng; Lin, Guosheng; Zhu, Chengang; Chen, Honglei; Yin, Jiechao; Jiang, Hong; Yang, Bo; Ding, Danhua

2008-10-01

The aim has been to determine whether the supernatants of mesenchymal stem cells (MSCs) transfected with adenovirus carrying human heme oxygenase-1 (hHO-1) gene protect cardiomyocytes from ischemic injury. We have found that hHO-1 infected MSCs (hHO-1-MSCs) increased expression of hHO-1 protein. Apoptosis of cultured hHO-1-MSCs exposed to hypoxia was suppressed. Several cytokines, including HGF, bFGF, TGF-beta, VEGF and IL-1beta, were produced by hHO-1-MSCs, some being significantly enhanced under hypoxia stimulation. Meanwhile, those cytokines reduced caspase-3 level and activity in cultured adult rat ventricular cardiomyocytes (ARVCs) exposed to hypoxia. Supernatants obtained from hHO-1-MSCs improved left ventricular function, limited myocardial infarct size, increased microvessel density, and inhibited apoptosis of cardiomyocytes in rat myocardial infarction. It can be concluded hHO-1-modified MSCs prevent myocardial cell injury via secretion of paracrine-acting mediators.

The reactions of HO2 with CO and NO and the reaction of O(1D) with H2O

NASA Technical Reports Server (NTRS)

Simonaitis, R.; Heicklen, J.

1973-01-01

HO2 radicals were generated by the photolysis of N2O at 2139 A in the presence of excess H2O or H2 and smaller amounts of CO and O2. The O(1D) atoms produced from the photolysis of N2O to give HO radicals or H2 to give HO + H. With H2O two HO radicals are produced for each O(1D) removed low pressures (i.e. approximately 20 torr H2O), but the HO yield drops as the pressure is raised. This drop is attributed to the insertion reaction: O(1D) + H2O + M yields H2O2 +M. The HO radicals generated can react with either CO or H2 to produce H atoms which then add to O2 to produce HO2. Two reactions are given for the reactions of the HO radicals, in the absence of NO.

Interagency Conflict Assessment Framework: A Pragmatic Tool for Army Design

DTIC Science & Technology

2010-12-02

Peter Checkland and John Poulter, Learning for Action: A Short Definitive Account of Soft Systems Methodology and its use for Practitioners, Teachers...lend itself to mechanistic analytical methods.32 Peter Checkland and John Poulter suggest that each approach is neither right nor wrong, rather...their relationships. According to Peter Checkland , the use of what he describes as “rich pictures” are excellent tools for capturing the dynamics of a

Theories of Power, Poverty, and Law: In Commemoration of the Contributions of Peter Bachrach--Empowerment and Poverty

ERIC Educational Resources Information Center

Levi, Margaret

2010-01-01

My subject is the way Peter Bachrach addressed the question of poverty. But given that I was his student and research assistant and that I am a political scientist largely because of him, it is impossible to resist a few words about the experience of being in his classrooms. Peter was an inspiring teacher of politics. The substantive content of…

AGU Publications Volunteers Feted At Elegant Editors' Evening

NASA Astrophysics Data System (ADS)

Panning, Jeanette

2013-01-01

The 2012 Fall Meeting Editors' Evening, held at the City Club of San Francisco, was hosted by the Publications Committee and is the premier social event for editors and associate editors attending the Fall Meeting. The evening commenced with a welcome from Carol Finn, incoming AGU president, in which she expressed her thanks to the editors and associate editors for volunteering their time to benefit AGU.

Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.

PubMed

Shigemori, Suguru; Watanabe, Takafumi; Kudoh, Kai; Ihara, Masaki; Nigar, Shireen; Yamamoto, Yoshinari; Suda, Yoshihito; Sato, Takashi; Kitazawa, Haruki; Shimosato, Takeshi

2015-11-25

Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. We developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD). We identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain. Oral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

Mechanical properties, in vitro corrosion and biocompatibility of newly developed biodegradable Mg-Zr-Sr-Ho alloys for biomedical applications

PubMed Central

Ding, Yunfei; Lin, Jixing; Wen, Cuie; Zhang, Dongmei; Li, Yuncang

2016-01-01

Our previous studies have demonstrated that Mg-Zr-Sr alloys can be anticipated as excellent biodegradable implant materials for load-bearing applications. In general, rare earth elements (REEs) are widely used in magnesium (Mg) alloys with the aim of enhancing the mechanical properties of Mg-based alloys. In this study, the REE holmium (Ho) was added to an Mg-1Zr-2Sr alloy at different concentrations of Mg1Zr2SrxHo alloys (x = 0, 1, 3, 5 wt. %) and the microstructure, mechanical properties, degradation behaviour and biocompatibility of the alloys were systematically investigated. The results indicate that the addition of Ho to Mg1Zr2Sr led to the formation of the intermetallic phases MgHo3, Mg2Ho and Mg17Sr2 which resulted in enhanced mechanical strength and decreased degradation rates of the Mg-Zr-Sr-Ho alloys. Furthermore, Ho addition (≤5 wt. %) to Mg-Zr-Sr alloys led to enhancement of cell adhesion and proliferation of osteoblast cells on the Mg-Zr-Sr-Ho alloys. The in vitro biodegradation and the biocompatibility of the Mg-Zr-Sr-Ho alloys were both influenced by the Ho concentration in the Mg alloys; Mg1Zr2Sr3Ho exhibited lower degradation rates than Mg1Zr2Sr and displayed the best biocompatibility compared with the other alloys. PMID:27553403

HO(x) Measurements in PEM Tropics B with the Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS)

NASA Technical Reports Server (NTRS)

Brune, William H.

2001-01-01

The primary objective of PEM Tropics B was to study the processes responsible for the production and loss of tropospheric ozone over the tropical Pacific. This region of the globe contains very clean air as well as aged, polluted air that was advected from both the Asian and American continents. Understanding ozone requires understanding of HO(x) (HO(x) = OH + HO2) chemistry, since the reaction between H02 and NO leads to ozone production and the production of OH often requires ozone loss. In addition, OH is the atmosphere's primary oxidant. Since most atmospheric oxidation is thought to occur in the tropical lower troposphere, measurements during PEM Tropics B should provide an important test of the OH abundances and distributions. Thus, understanding and thoroughly testing HO(x) processes was an important objective of PEM Tropics B. Several issues need to be tested, One is HO, production rates and sources, since HO,, production directly affects ozone production and loss. Another is HO(x) behavior in and around clouds, since HO(x) is lost to cloud particles, but convection may bring HO(x) precursors from near the surface to the upper troposphere. A third is the rise and fall of HO(x) at sunrise and sunset, since these variations give strong indications of the important sources and sinks of HO(x). Making and interpreting high-quality OH and H02 measurements from the NASA DC-8 during PEM Tropics B is the objective of this research effort.

Reduction of bilirubin by targeting human heme oxygenase-1 through siRNA.

PubMed

Xia, Zhen-Wei; Li, Chun-E; Jin, You-Xin; Shi, Yi; Xu, Li-Qing; Zhong, Wen-Wei; Li, Yun-Zhu; Yu, Shan-Chang; Zhang, Zi-Li

2007-04-01

Neonatal hyperbilirubinemia is a common clinical condition caused mainly by the increased production and decreased excretion of bilirubin. Current treatment is aimed at reducing the serum levels of bilirubin. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that generates bilirubin. In this study we intended to suppress HO-1 using the RNA interference technique. Small interfering RNA (siRNA)-A, -B, and -C were designed based on human HO-1 (hHO-1) mRNA sequences. siRNA was transfected into a human hepatic cell line (HL-7702). hHO-1 transcription and protein levels were then determined. In addition, the inhibitory effect of siRNA on hHO-1 was assessed in cells treated with hemin or transfected with an hHO-1 plasmid. siRNA-C showed the most potent suppressive effect on hHO-1. This inhibition is dose and time dependent. Compared with control, both hemin and hHO-1 plasmids up-regulated hHO-1 expression in HL-7702 cells. However, the up-regulation was significantly attenuated by siRNA-C. Furthermore, the decrease in hHO-1 activity was coincident with the suppression of its transcription. Finally, siRNA-C was shown to reduce hHO-1 enzymatic activity and bilirubin levels. Thus, this study provides a novel therapeutic rationale by blocking bilirubin formation via siRNA for preventing and treating neonatal hyperbilirubinemia and bilirubin encephalopathy at an early clinical stage.

An inter-comparison of HO2 measured by Fluorescence Assay by Gas Expansion and Cavity Ringdown Spectroscopy in the Highly Instrumented Reactor for Atmospheric Chemistry.

NASA Astrophysics Data System (ADS)

Brennan, A.; Onel, L. C.; Gianella, M.; Ronnie, G.; Aguila, A. L.; Hancock, G.; Whalley, L.; Seakins, P. W.; Ritchie, G.; Heard, D. E.

2017-12-01

HO2 is an important species in the atmosphere, as it is involved in the HOx radical reaction cycle that is critical to the oxidation of atmospheric pollutants and the ultimate cleaning of the troposphere. One of the most widely utilised methods to measure HO2 is Fluorescence Assay by Gas Expansion (FAGE), which indirectly measures HO2 by sampling into a low pressure cell and titrating HO2 with NO to produce OH that is then detected by Laser Induced Fluorescence. This is an indirect and non-absolute detection technique that requires careful calibration to convert the measured signal into [HO2], which involves the photolysis of H2O at 185 nm to produce OH and HO2, and is subject to 30 % errors at 2σ level. The work presented here shows the validation of the FAGE technique and its calibration procedure through inter-comparison experiments between the non-absolute FAGE technique and Cavity Ringdown Spectroscopy (CRDS), an absolute absorption based method. The CRDS system was used to excite the first O-H overtone of the HO2 absorption band at 1506.43 nm, and features a cavity length of 1.2 m and a total path of 60 km. The experiments were performed inside the 2.25 m3 stainless steel Highly Instrumented Reactor for Atmospheric Chemistry (HIRAC), using a synthetic air mixture at 150 and 1000 mbar of pressure and 298 K. HO2 was generated by photolysis of Cl2 at 365 nm in the presence of CH3OH and O2, and the [HO2] was monitored using both instruments. Additionally, monitoring the temporal decay of HO2 during its self-reaction provided an alternative calibration method for the FAGE instrument, and allowed the absorption cross section of HO2 at 1506.43 nm, σHO2, to be measured. FAGE calibration factors determined through the second order decays of HO2 at 1000 mbar agreed within 8 % of the H2O photolysis method, and determinations of σHO2 at 150 and 1000 mbar agree with previously reported data within 20 % and 12 % respectively. [HO2] correlation plots between the two instruments at 150 and 1000 mbar showed very good agreements of 0.863 ± 0.004 and 0.903 ± 0.002 respectively. This consistency between the indirect FAGE and direct CRDS measurements of HO2 validates the FAGE method, which is widely used for field measurements of HO2 in the troposphere.

Production, fertility, survival, and body measurements of Montbéliarde-sired crossbreds compared with pure Holsteins during their first 5 lactations.

PubMed

Hazel, A R; Heins, B J; Seykora, A J; Hansen, L B

2014-01-01

Two-breed crossbreds of Montbéliarde and Holstein (MO × HO) as well as 3-breed crossbreds of Montbéliarde and Jersey/Holstein (MO × JH) were compared with pure Holstein (HO) cows for production, somatic cell score (SCS), fertility, survival to subsequent calving, mortality, and body measurements during their first 5 lactations. Cows calved for the first time between 2005 and 2010 and were housed in either a confinement herd or a herd that had access to pasture for 165d of the year in the north central region of the United States. Body, hoof, and udder measurements of cows were also objectively measured. The MO × HO crossbred cows were not different from pure HO cows for fat-plus-protein production during any lactation. However, the MO × JH crossbred cows had 5% lower fat-plus-protein production compared with pure HO cows in the confinement herd. On the other hand, the MO × JH crossbred cows were not different for fat-plus-protein production in the third to fifth lactation compared with pure HO cows in the seasonal pasture herd. Across the 2 herds, the MO × HO and MO × JH crossbred cows had 21% higher first-service conception rate, 41 fewer days open, and 12% higher pregnancy rate compared with the pure HO cows. Furthermore, the MO × HO (5%) and MO × JH (12%) crossbred cows had lower mortality rates than the pure HO cows (18%). Because of superior fertility and lower mortality rates, the MO × HO and MO × JH crossbred cows, combined, had greater survival to second (+13%), third (+24%), fourth (+25%), and fifth (+17%) lactation compared with pure HO cows. For body measurements, MO × HO were similar to pure HO cows for hip height and heart girth, but MO × HO cows had more body condition and greater body weight (+39kg) across the first 5 lactations. The MO × JH cows had more body condition but 5cm shorter hip height and 28kg less body weight than pure HO cows across the first 5 lactations. Foot angle was steeper and hoof length was shorter for MO × HO cows, but MO × JH cows were similar to pure HO cows for hoof measurements. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

High Energy Directly Pumped Ho:YLF Laser

NASA Technical Reports Server (NTRS)

Petros, Mulugeta; Yu, Ji-Rong; Singh, Upendra N.; Barnes, Norman P.

2000-01-01

The most commonly used crystal architecture to produce 2 micrometer laser is co-doping Ho and Tm into a single host crystal. In this method, the stored energy transfer from the Tm (3)F4 to the Ho (5)I7 manifold is not fast enough to warrant high efficiency for short pulse applications. By separating the Ho and the Tm ions and doping the Tm in YALO3 and the Ho in YLF, we were able to directly pump the Ho (5)I7 manifold with 1.94 micrometers. The Ho:YLF laser has produced 33 mJ at 2.062 micrometers with a quantum efficiency of 0.88. The performance of each laser will be presented.

Preparation and spectroscopic characterization of two HoCl 3-galactitol complexes and one ErCl 3-galactitol complex

NASA Astrophysics Data System (ADS)

Hua, Xiaohui; Pan, Qinghua; Yu, Lei; Xue, Junhui; Yang, Limin; Xu, Yizhuang; Zhao, Guozhong; Li, Weihong; Wang, Zheming; Wu, Jinguang; Liu, Kexin; Chen, Jia'er

2011-07-01

The interactions between metal ions and hydroxyl groups of carbohydrates are important for their possible biological activities. Here two HoCl 3-galactitol complexes ([Ho(galac)(H 2O) 3)]Cl 3·0.5galac) (HoG(I)) and ([Ho 2(galac)(H 2O) 12)]Cl 6·2H 2O) (HoG(II))) and one ErCl 3-galactitol complex ([Er(galac)(H 2O) 3)]Cl 3·0.5galac)(ErG)) were prepared and characterized. The possible structures of HoG(I) and ErG were deduced from FTIR, elemental analysis, ESI-MS, FIR, THz and TGA results. It is suggested that Ho 3+ or Er 3+ is 9-coordinated with six hydroxyl groups from two galactitol molecules and three water molecules, and another galactitol molecule is hydrogen-bonded in HoG(I) and ErG and the ratio of metal to ligand is 1:1.5. The structure of HoG(II) was determined by FTIR and X-ray diffraction analyses. The results demonstrate that lanthanide ions with galactitol may form two compounds in a system and different topological structures can be obtained.

Do Postoperative Biomechanical Changes Induce Heterotopic Ossification After Cervical Arthroplasty?: A 5-Year Follow-up Study.

PubMed

Kim, Keun Su; Heo, Dong Hwa

2016-07-01

Prospective clinical study. To evaluate the factors that would predispose a patient to heterotopic ossification (HO) formation after cervical arthroplasty. HO after arthroplasty is one of the complications of cervical total disk replacement (TDR). However, the predisposing factors and pathophysiology of HO have not been precisely described. We prospectively enrolled and followed up 23 patients, who received single-level arthroplasty with ProDisc-C, for 5 years after the operation. The patients who developed grade 3 or 4 HO were classified into the "high-grade HO group," whereas the patients with grade 0, 1, or 2 HO were classified into the "low-grade HO group." We compared the postoperative changes in the range of motion (ROM) and height of the functional segmental unit (FSU) of the implantation segments between the 2 groups. The mean differences in height and ROM of the FSU were 2.59±1.42 mm and 6.7±3.2 degrees in the high-grade HO group, and 0.87±0.72 mm and 3.1±2.8 degrees in the low-grade HO group. The mean differences in height and ROM of the FSU were significantly higher in the high-grade HO group than in the low-grade HO group (P<0.05). After cervical arthroplasty, the height of the FSU and ROM of the implantation segments were significantly increased in the high-grade HO group compared with the low-grade HO group. Overcorrection of the height of the FSU and increase in the ROM of the implantation segment may influence the formation of HOs after cervical arthroplasty.

Protein/Protein Interactions in the Mammalian Heme Degradation Pathway

PubMed Central

Spencer, Andrea L. M.; Bagai, Ireena; Becker, Donald F.; Zuiderweg, Erik R. P.; Ragsdale, Stephen W.

2014-01-01

Heme oxygenase (HO) catalyzes the rate-limiting step in the O2-dependent degradation of heme to biliverdin, CO, and iron with electrons delivered from NADPH via cytochrome P450 reductase (CPR). Biliverdin reductase (BVR) then catalyzes conversion of biliverdin to bilirubin. We describe mutagenesis combined with kinetic, spectroscopic (fluorescence and NMR), surface plasmon resonance, cross-linking, gel filtration, and analytical ultracentrifugation studies aimed at evaluating interactions of HO-2 with CPR and BVR. Based on these results, we propose a model in which HO-2 and CPR form a dynamic ensemble of complex(es) that precede formation of the productive electron transfer complex. The 1H-15N TROSY NMR spectrum of HO-2 reveals specific residues, including Leu-201, near the heme face of HO-2 that are affected by the addition of CPR, implicating these residues at the HO/CPR interface. Alanine substitutions at HO-2 residues Leu-201 and Lys-169 cause a respective 3- and 22-fold increase in Km values for CPR, consistent with a role for these residues in CPR binding. Sedimentation velocity experiments confirm the transient nature of the HO-2·CPR complex (Kd = 15.1 μm). Our results also indicate that HO-2 and BVR form a very weak complex that is only captured by cross-linking. For example, under conditions where CPR affects the 1H-15N TROSY NMR spectrum of HO-2, BVR has no effect. Fluorescence quenching experiments also suggest that BVR binds HO-2 weakly, if at all, and that the previously reported high affinity of BVR for HO is artifactual, resulting from the effects of free heme (dissociated from HO) on BVR fluorescence. PMID:25196843

Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase

PubMed Central

Hull, Travis D.; Bolisetty, Subashini; DeAlmeida, Angela; Litovsky, Silvio H.; Prabhu, Sumanth D.; Agarwal, Anupam; George, James F.

2013-01-01

The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (MHC-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice) with mice containing an hHO-1 transgene preceded by a floxed stop signal (CBA-flox mice). MHC-HO-1 overexpress the HO-1 gene and enzymatically protein following TAM administration (40 mg/kg body weight on two consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity and also because inflammation is an important pathological component of many human cardiovascular diseases. PMID:23732814

Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

PubMed

Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

2013-08-01

The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

High-frequency spectral ultrasound imaging (SUSI) visualizes early post-traumatic heterotopic ossification (HO) in a mouse model.

PubMed

Ranganathan, Kavitha; Hong, Xiaowei; Cholok, David; Habbouche, Joe; Priest, Caitlin; Breuler, Christopher; Chung, Michael; Li, John; Kaura, Arminder; Hsieh, Hsiao Hsin Sung; Butts, Jonathan; Ucer, Serra; Schwartz, Ean; Buchman, Steven R; Stegemann, Jan P; Deng, Cheri X; Levi, Benjamin

2018-04-01

Early treatment of heterotopic ossification (HO) is currently limited by delayed diagnosis due to limited visualization at early time points. In this study, we validate the use of spectral ultrasound imaging (SUSI) in an animal model to detect HO as early as one week after burn tenotomy. Concurrent SUSI, micro CT, and histology at 1, 2, 4, and 9weeks post-injury were used to follow the progression of HO after an Achilles tenotomy and 30% total body surface area burn (n=3-5 limbs per time point). To compare the use of SUSI in different types of injury models, mice (n=5 per group) underwent either burn/tenotomy or skin incision injury and were imaged using a 55MHz probe on VisualSonics VEVO 770 system at one week post injury to evaluate the ability of SUSI to distinguish between edema and HO. Average acoustic concentration (AAC) and average scatterer diameter (ASD) were calculated for each ultrasound image frame. Micro CT was used to calculate the total volume of HO. Histology was used to confirm bone formation. Using SUSI, HO was visualized as early as 1week after injury. HO was visualized earliest by 4weeks after injury by micro CT. The average acoustic concentration of HO was 33% more than that of the control limb (n=5). Spectroscopic foci of HO present at 1week that persisted throughout all time points correlated with the HO present at 9weeks on micro CT imaging. SUSI visualizes HO as early as one week after injury in an animal model. SUSI represents a new imaging modality with promise for early diagnosis of HO. Copyright © 2018 Elsevier Inc. All rights reserved.

Sofalcone, a gastric mucosa protective agent, increases vascular endothelial growth factor via the Nrf2-heme-oxygenase-1 dependent pathway in gastric epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shibuya, Akiko; Onda, Kenji, E-mail: knjond@toyaku.ac.jp; Kawahara, Hirofumi

2010-07-30

Research highlights: {yields} Sofalcone increases HO-1 in gastric epithelial cells. {yields} The induction of HO-1 by sofalcone treatment follows the activation of Nrf2. {yields} The production of VEGF by sofalcone treatment is mediated by HO-1 induction. -- Abstract: Sofalcone, 2'-carboxymethoxy-4,4-bis(3-methyl-2-butenyloxy)chalcone, is an anti-ulcer agent that is classified as a gastric mucosa protective agent. Recent studies indicate heat shock proteins such as HSP32, also known as heme-oxygenase-1(HO-1), play important roles in protecting gastrointestinal tissues from several stresses. We have previously reported that sofalcone increases the expression of HO-1 in adipocytes and pre-adipocytes, although the effect of sofalcone on HO-1 induction inmore » gastrointestinal tissues is not clear. In the current study, we investigated the effects of sofalcone on the expression of HO-1 and its functional role in rat gastric epithelial (RGM-1) cells. We found that sofalcone increased HO-1 expression in RGM-1 cells in both time- and concentration-dependent manners. The HO-1 induction was associated with the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in RGM-1 cells. We also observed that sofalcone increased vascular endothelial growth factor (VEGF) production in the culture medium. Treatment of RGM-1 cells with an HO-1 inhibitor (tin-protoporphyrin), or HO-1 siRNA inhibited sofalcone-induced VEGF production, suggesting that the effect of sofalcone on VEGF expression is mediated by the HO-1 pathway. These results suggest that the gastroprotective effects of sofalcone are partly exerted via Nrf2-HO-1 activation followed by VEGF production.« less

Effects of treatment of periparturient dairy cows with recombinant bovine somatotropin on health and productive and reproductive parameters.

PubMed

Silva, P R B; Soares, H F; Braz, W D; Bombardelli, G D; Clapper, J A; Keisler, D H; Chebel, R C

2017-04-01

The objectives of the current experiment were to evaluate the effects of treating periparturient dairy cows with recombinant bovine somatotropin (rbST) on incidence of postpartum diseases and performance. Holstein (HO) and Jersey (JS) cows from 2 herds were enrolled in the experiment at 253 ± 3 d of gestation and assigned to the control (n = 432) and rbST125 (n = 437) treatments. Cows in the rbST125 treatment received 125 mg of rbST, weekly, from -21 to 21 d relative to calving. Blood sampled weekly, from -21 to 21 d relative to calving, from a subsample of cows was used to determine the concentrations of growth hormone (GH, HO = 106) and insulin-like growth factor 1 (IGF-1, HO = 147 and JS = 49). Cows were scored for body condition (BCS) at enrollment and at 1 ± 3, 30 ± 3, and 60 ± 3 d in milk (DIM). Cows were milked thrice daily and energy-corrected milk (ECM) yield was recorded for the first 30 DIM. Treatment of cows with rbST resulted in greater concentrations of GH during the prepartum (log 10 back-transformed concentrations of GH: HO-control = 7.83 and HO-rbST125 = 10.36 ng/mL) and postpartum (log 10 back-transformed concentrations of GH: HO-control = 10.45 and HO-rbST125 = 18.47 ng/mL) periods. Similarly, IGF-1 concentrations were higher during the prepartum (HO-control = 115.1 ± 4.9, HO-rbST125 = 137.7 ± 4.7, JS-control = 120.2 ± 8.3, JS-rbST125 = 167.1 ± 8.1 ng/mL) and postpartum (HO-control = 61.3 ± 4.0, HO-rbST125 = 75.2 ± 3.8, JS-control = 35.5 ± 6.9, JS-rbST125 = 54.6 ± 6.9 ng/mL) periods for rbST-treated cows. During the prepartum period, BCS was not affected by treatment, but during the postpartum period, BCS was reduced for rbST-treated cows (HO-control = 3.00 ± 0.03, HO-rbST125 = 2.90 ± 0.03, JS-control = 2.64 ± 0.02, JS-rbST125 = 2.61 ± 0.02). Cows from the rbST125 treatment tended to have lower incidence of retained fetal membranes (HO-control = 14.3, HO-rbST125 = 6.1, JS-control = 1.5, JS-rbST125 = 1.2%) and had reduced incidence of metritis (HO-control = 26.2, HO-rbST125 = 16.6, JS-control = 19.9, JS-rbST125 = 13.3%) compared with control cows. Ketosis incidence tended to be higher for rbST125 cows (HO-control = 9.4, HO-rbST125 = 11.3, JS-control = 8.5, JS-rbST125 = 13.4%) compared with control cows. The interaction between treatment and herd tended to affect yield of ECM during the first 30 DIM because HO cows treated with rbST during the periparturient period had greater yield than control HO cows (HO-control = 35.5 ± 1.0 vs. HO-rbST125 = 39.4 ± 1.0 kg/d), but treatment with rbST did not affect yield of ECM of JS cows (JS-control = 26.7 ± 0.6 vs. JS-rbST125 = 27.8 ± 0.6 kg/d). Treatment of periparturient dairy cows with 125 mg of rbST decreased the incidence of uterine disorders in HO and JS cows and increased yield of ECM during the first 30 DIM among HO cows, despite slightly increasing the incidence of ketosis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Deflection in Tapered Cantilever Beams Deflection (Gap Opening) in Double Cantilever Type Fracture Toughness Specimens.

DTIC Science & Technology

1985-08-01

o10 ------- --------- tx] (26) t 5 t bE ho 2(h0+tx) 2 and as before 12 9 1 p ho + tx 2ho + 3tx bend3 + bE ho 2(ho+tX)2 txcos2 At the limit, as t...h0+tx) 2tx Therefore P 1 x P x lim 6 bend3 n2 -(-) - 4 -(;) t+o bE 3ho bE h 22 which, except for the sign, is the same as that arrived at in Eq. (9

Actively mode-locked Tm-Ho:LiYF4 and Tm-Ho:BaY2F8 lasers

NASA Astrophysics Data System (ADS)

Gatti, D.; Galzerano, G.; Toncelli, A.; Tonelli, M.; Laporta, P.

2007-01-01

We report on the generation of mode-locking pulse trains with high average output powers from diode-pumped Tm-Ho:LiYF4 and Tm-Ho:BaY2F8 lasers emitting at around 2 μm. The highest output power of 365 mW was obtained with the Tm-Ho:YLF4 laser, whereas the shortest pulse duration of 120 ps and the widest tunability range of 59 nm was achieved with the Tm-Ho:BaY2F8 laser.

XVII International Conference on the Use of Computers in Radiation Therapy (ICCR 2013)

NASA Astrophysics Data System (ADS)

2014-03-01

Editorial Dear colleagues, From a professional perspective there is nothing quite as enjoyable as attending a good conference with colleagues that share not only interest for the same topic but also a similar vision for their field of work. Proceedings cannot replace the direct contact and lively conversations between participants who are at the same time at the same place sharing ideas and discussion. However, proceedings complement the actual conference by 1. giving the ideas, research findings and debates which characterise the conference lasting presence 2. giving participants an opportunity to refresh their memory about issues they would like to follow up on and 3. providing an opportunity for others who were not able to attend the meeting to share in the thoughts and issues discussed at the conference. For the proceedings of the International Conferences on the Use of Computers in Radiation Therapy (ICCR) all this has been important in the past as the high citation rates for ICCR proceedings show. We hope that also the present proceedings will appeal to participants and others who are interested in cancer and ways to treat patients affected by it. It is exciting to note that what sounded like a small niche field (''Computers in Radiation Therapy'') has become a very broad forum to discuss all aspects of cancer diagnosis and therapy. Of particular interest for the 17th ICCR have been data and how to collect, organise and use it effectively. This is relevant for most areas in medicine and we believe that radiation therapy with its focus on evidence based practice and measurable and standardised activities has an important and possibly leading role to play. The 100 manuscripts combined in the present proceedings can hopefully contribute to this. The proceedings are organised into five different streams which reflect the foci of the conference: • Dose Calculation • Imaging for treatment planning and Motion Management • Treatment planning and optimisation • Verification, Risk assessment and IGRT • Trials, registries and more Each of the streams had its own theme editor and we would like to thank Peter Greer, Sarah Gulliford, Tomas Janssen, Joerg Lehmann and Peter Metcalfe and for their invaluable contributions. I believe we all shared the joy of reading the huge variety of manuscripts which reflect a dynamic field and a truly international authorship. All manuscripts have been peer reviewed by at least two independent referees. Still, proceedings are different from journal articles. The focus of the proceedings is on interest for others, novelty and creativity. While trying to ensure a common format to all contributions we have also aimed to maintain the style and approach of the individual authors. We would like to thank all authors and reviewers for their contribution to these ICCR proceedings. On behalf of the editorial team we would like to invite you to explore the proceedings and hope that you enjoy reading them as much as we did editing them. Yours sincerely Annette Haworth and Tomas Kron Editors, Proceedings of the 17th ICCR

A Central Role for Heme Oxygenase-1 in the Control of Intestinal Epithelial Chemokine Expression.

PubMed

Onyiah, Joseph C; Schaefer, Rachel E M; Colgan, Sean P

2018-05-23

In mucosal inflammatory disorders, the protective influence of heme oxygenase-1 (HO-1) and its metabolic byproducts, carbon monoxide (CO) and biliverdin, is a topic of significant interest. Mechanisms under investigation include the regulation of macrophage function and mucosal cytokine expression. While there is an increasing recognition of the importance of epithelial-derived factors in the maintenance of intestinal mucosal homeostasis, the contribution of intestinal epithelial cell (IEC) HO-1 on inflammatory responses has not previously been investigated. We examined the influence of modulating HO-1 expression on the inflammatory response of human IECs. Engineered deficiency of HO-1 in Caco-2 and T84 IECs led to increased proinflammatory chemokine expression in response to pathogenic bacteria and inflammatory cytokine stimulation. Crosstalk with activated leukocytes also led to increased chemokine expression in HO-1-deficient cells in an IL-1β dependent manner. Treatment of Caco-2 cells with a pharmacological inducer of HO-1 led to the inhibition of chemokine expression. Mechanistic studies suggest that HO-1 and HO-1-related transcription factors, but not HO-1 metabolic products, are partly responsible for the influence of HO-1 on chemokine expression. In conclusion, our data identify HO-1 as a central regulator of IEC chemokine expression that may contribute to homeo-stasis in the intestinal mucosa. © 2018 S. Karger AG, Basel.

Heme oxygenase: the key to renal function regulation

PubMed Central

Cao, Jian; Sacerdoti, David; Li, Xiaoying; Drummond, George

2009-01-01

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function. PMID:19570878

DOE Office of Scientific and Technical Information (OSTI.GOV)

Başar, Gö.; Güzelçimen, F.; Er, A.

Fourier Transform spectra of holmium (Ho) in the UV spectral range from 31,530 to 25,000 cm{sup −1} (317 to 400 nm) have been investigated, particularly focusing on the ionic lines. The distinction between the different degrees of ionization (I, II, and III) is based on differences in signal-to-noise ratios from two Ho spectra, which have been measured with different buffer gases, i.e., neon and argon. Based on 106 known Ho ii and 126 known Ho iii energy levels, 97 lines could be classified as transitions of singly ionized Ho and 9 lines could be classified as transitions of doubly ionized Ho.more » Of the 97 Ho ii lines, 6 have not been listed in the extant literature. Another 215 lines have been assigned to Ho ii, though they could not be classified on the basis of the known energy levels.« less

Peter the Great: Linking Military Strategy to National Objectives in Imperial Russia

DTIC Science & Technology

1999-04-01

provisions) and because its forces could not move fast enough to overcome the Ottoman’s delaying tactics.1 Vasili Golitsyn, Alexei’s representative to...conclusion when, in 1694, he pitted six Streltsy regiments against his two new Guards regiments (Preobrazhenskii and Semenovskii) in mock combat. The...Press, 1971. Gray, Ian. Peter the Great: Emperor of all Russia. New York: J.B.Lippincott, 1960. Klychevsky, Vasili . Peter the Great. Boston: Beacon

Immersive Environments in ADL

DTIC Science & Technology

2009-08-20

Tracking and Storing In Browser 3-D 13 Questions or Comments? Peter Smith Team Lead, Immersive Learning Technologies peter.smith.ctr@adlnet.gov +1.407.384.5572 ...Immersive Environments in ADL Mr. Peter Smith, Lead, ADL Immersive Learning Team 08/20/2009 Report Documentation Page Form ApprovedOMB No. 0704-0188...5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Advanced Decision Learning (ADL),1901 N

Konrad Adenauer’s Military Advisors

DTIC Science & Technology

1989-02-13

Ausgabe. Hans-Peter Schwarz and 45 Rudolf Morsey, Hg. Vol. 1, Briefe 1945-1947 hg. v. Hans Peter Mensing. Berlin: Siedler Verlag, 1983. Vol. 2, Briefe 1949...Dietrich, Rudolf Morsey and Hans-Peter Schwarz, ed. Quellen zur Geschichte des Parlarnentarismus und der politischen Partein. Bd. 3, Auftakt zur Ara...New York: Penguin, 1982. Steiner , Jirg. European Democracies. New York: Longman, 1986. Taylor, A.J.P. The Origens of the Second World War. 2d. ed. New

Set Based Program Analysis

DTIC Science & Technology

1992-10-01

Philosophy Thesis Committee: Peter Lee, Co-Chair Frank Pfenning, Co-chair Dana Scott Joxan Jaffar, IBM Neil Jones, DIKU, Copenhagen Copyright C 1992...much of this thesis represents joint work with him. I am also indebted to Peter Lee and Frank Pfenning, my advisors at CMU. Their encouragement...I am very grateful to Peter , Frank, Joxan and CMU that this has been a synergistic experience. I would like to thank Neil Jones and Dana Scott for

Enhancing Osteoclastic Resorption for the Prevention and Treatment of Heterotopic Ossification

DTIC Science & Technology

2015-03-01

two thirds of these patients developing painful and debilitating HO. There are currently no effective treatments for HO other than surgical...prevention and treatment of HO, to relieve this painful and debilitating orthopaedic complication. American Society for Bone and Mineral Research, Houston...developing painful and debilitating HO. There are currently no effective treatments for HO other than surgical excision of the ossified tissue which

Magnetic and magnetocaloric properties of iron subs tituted holmium chromite and dysprosium chromite

DOE PAGES

Yin, Shiqi; Sharma, Vinit; McDannald, Austin; ...

2016-01-11

In this work, structural, magnetic, and magnetocaloric properties of HoCrO 3 and Fe substituted HoCrO 3 and DyCrO 3 (i.e. HoCr 0.7Fe 0.3O 3 and DyCr 0.7Fe 0.3O 3) powder samples were synthesized via a solution route. The structural properties of the samples were examined by Raman spectroscopy and x-ray diffraction techniques, which were further confirmed using first-principle calculations. The dc magnetic measurements indicate that the Cr 3+ ordering temperatures for the HoCrO 3, HoCr 0.7Fe 0.3O 3, and DyCr 0.7Fe 0.3O 3 samples are 140 K, 174 K, and 160 K, respectively. The ac magnetic measurements not only confirmedmore » the Cr 3+ ordering transitions in these samples (obtained using dc magnetic measurements), but also clearly showed the Ho 3+ ordering at ~10 K in the present HoCrO 3 and HoCr 0.7Fe 0.3O 3 samples, which to our knowledge, is the first ac magnetic evidence of Ho 3+ ordering in this system. The effective magnetic moments were determined to be 11.67μB, 11.30μB, and 11.27μB for the HoCrO 3, HoCr 0.7Fe 0.3O 3, and DyCr 0.7Fe 0.3O 3 samples, respectively. For the first time, the magnetocaloric properties of HoCrO 3 and HoCr 0.7Fe 0.3O 3 were studied here, showing their potential for applications in magnetic refrigeration. In an applied dc magnetic field of 7 T, the maximum magnetocaloric value were determined to be 7.2 (at 20 K), 6.83 (at 20 K), 13.08 J/kg K (at 5 K) and the relative cooling power were 408, 387, and 500 J/kg for the HoCrO 3, HoCr 0.7Fe 0.3O 3, and DyCr 0.7Fe 0.3O 3 samples, respectively.« less

Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jin-Sun; Kim, Hee-Sun, E-mail: hskimp@ewha.ac.kr

2014-05-16

Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigatedmore » the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes.« less

Molecular cloning, characterization, and expression of an alfalfa (Medicago sativa L.) heme oxygenase-1 gene, MsHO1, which is pro-oxidants-regulated.

PubMed

Fu, Guang-Qing; Xu, Sheng; Xie, Yan-Jie; Han, Bin; Nie, Li; Shen, Wen-Biao; Wang, Ren

2011-07-01

It has been documented that plant heme oxygenase-1 (HO-1; EC 1.14.99.3) is both development- and stress-regulated, thus it plays a vital role in light signalling and stress responses. In this study, an alfalfa (Medica sativa L.) HO-1 gene MsHO1 was isolated and sequenced. It contains four exons and three introns within genomic DNA sequence and encodes a polypeptide with 283 amino acids. MsHO1 had a conserved HO signature sequence and showed high similarity to other HOs in plants, especially HO-1 isoform. The MsHO1:GFP fusion protein was localized in the chloroplast. Further biochemical activity analysis of mature MsHO1, which was expressed in Escherichia coli, showed that the Vmax was 48.78 nmol biliverdin-IXα (BV) h⁻¹ nmol⁻¹ protein with an apparent Km value for hemin of 2.33 μM, and the optimum Tm and pH were 37 °C and 7.2, respectively. Results of semi-quantitative RT-PCR and western blot showed that the expressions of MsHO1 were higher in alfalfa stems and leaves than those in germinating seeds and roots. Importantly, MsHO1 gene expression and protein level were induced significantly by some pro-oxidant compounds, including hemin and nitric oxide (NO) donor sodium nitroprusside (SNP). In conclusion, MsHO1 may play an important role in oxidative responses. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Regulation of rat heme oxygenase-1 expression by interleukin-6 via the Jak/STAT pathway in hepatocytes.

PubMed

Tron, Kyrylo; Samoylenko, Anatoly; Musikowski, Gernot; Kobe, Fritz; Immenschuh, Stephan; Schaper, Fred; Ramadori, Giuliano; Kietzmann, Thomas

2006-07-01

Heme oxygenase-1 (HO-1) can be induced by various stimuli, one of which is interleukin-6 (IL-6). Therefore, the aim of this study was to elucidate the molecular mechanisms responsible for IL-6-dependent HO-1 induction in the liver. The IL-6-dependent HO-1 regulation in rat primary hepatocytes and HepG2 hepatoma cells was studied by Northern and Western blot analyses, HO-1 promoter reporter gene assays and EMSA. The HO-1 expression was transcriptionally induced by IL-6 in a time- and dose-dependent manner. Activation of signal transducers and activators of transcription (STAT) factors by the IL-6 receptor was crucial for HO-1 induction. By contrast, negative regulation of HO-1 expression appeared to be mediated through the SH2-domain-containing tyrosine phosphatase-2 (SHP2)/ suppressors of cytokine signaling-3 (SOCS3) binding site within the gp130 IL-6 receptor subunit. Among the three putative STAT binding elements (SBE) in the HO-1 promoter, only the distal one was functional and when deleted, the remaining Luc induction was completely obliterated by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. The HO-1 SBE3 mediates HO-1 gene induction by IL-6 mainly via activation of the Jak/STAT pathway.

The effect of moderate-intensity exercise on the expression of HO-1 mRNA and activity of HO in cardiac and vascular smooth muscle of spontaneously hypertensive rats.

PubMed

Ren, Cailing; Qi, Jie; Li, Wanwei; Zhang, Jun

2016-04-01

The objective of this study was to observe the effects of moderate-intensity training on the activity of heme oxygenase (HO) and expression of HO-1 mRNA in the aorta and the cardiac muscle of spontaneously hypertensive rats (SHRs). After 9 weeks of swimming exercise, the activity of HO and expression of HO-1 mRNA in the SHRs were measured. The resting blood pressure in the exercise group was increased by 1.7% (P > 0.05), whereas it was significantly elevated by 10.3% (P < 0.01) in the SHR rats. Compared with animals in the control and sedentary groups, the expression level of HO-1 mRNA of aorta and cardiac muscle in the exercise group was significantly enhanced (P < 0.01). The HO activity and the content of plasma carbon monoxide (CO) in the sedentary group were dramatically decreased (P < 0.05 and P < 0.01, respectively) compared with the control group. HO activity and content of plasma CO in the exercise group were significantly higher compared with those in the sedentary group (P < 0.05 and P < 0.01, respectively). The HO/CO metabolic pathway might be involved in the regulation of blood pressure of the SHR models.

Heterogeneous reaction of HO2 with airborne TiO2 particles and its implication for climate change mitigation strategies

NASA Astrophysics Data System (ADS)

Moon, Daniel R.; Taverna, Giorgio S.; Anduix-Canto, Clara; Ingham, Trevor; Chipperfield, Martyn P.; Seakins, Paul W.; Baeza-Romero, Maria-Teresa; Heard, Dwayne E.

2018-01-01

One geoengineering mitigation strategy for global temperature rises resulting from the increased concentrations of greenhouse gases is to inject particles into the stratosphere to scatter solar radiation back to space, with TiO2 particles emerging as a possible candidate. Uptake coefficients of HO2, γ(HO2), onto sub-micrometre TiO2 particles were measured at room temperature and different relative humidities (RHs) using an atmospheric pressure aerosol flow tube coupled to a sensitive HO2 detector. Values of γ(HO2) increased from 0.021 ± 0.001 to 0.036 ± 0.007 as the RH was increased from 11 to 66 %, and the increase in γ(HO2) correlated with the number of monolayers of water surrounding the TiO2 particles. The impact of the uptake of HO2 onto TiO2 particles on stratospheric concentrations of HO2 and O3 was simulated using the TOMCAT three-dimensional chemical transport model. The model showed that, when injecting the amount of TiO2 required to achieve the same cooling effect as the Mt Pinatubo eruption, heterogeneous reactions between HO2 and TiO2 would have a negligible effect on stratospheric concentrations of HO2 and O3.

The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

PubMed

Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

2013-12-01

Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

Feasibility Study of a Novel Diet-Based Intervention for Prostate Cancer

DTIC Science & Technology

2011-09-01

Trial of Diet to Alter Disease Progression in Prostate Cancer Patients on Active Surveillance.” Peter Van Veldhuizen , Jr., MD will be joining the...Administrator Nathan Eriksen SWOG Prevention Committee Chairs Powel H. Brown, MD, PhD Gary E. Goodman, MD New SWOG Co-Chair Peter Van Veldhuizen , Jr...above. The Cancer and Leukemia Group B (CALGB) will be responsible for circulating all revisions of the protocol to Dr. Peter Van Veldhuizen , Jr

Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer

DTIC Science & Technology

2001-10-01

Genetic Markers of the Invasive Phenotype in Human Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Peter Watson CONTRACTING ORGANIZATION: University of...Markers of the Invasive Phenotype DAMD17-97-1-7320 in Human Breast Cancer 6. AUTHOR(S) Dr. Peter Watson 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...markers of the invasive phenotype in human breast cancer" Dr Peter H. Watson INTRODUCTION. The acquisition of the ability to invade is the single most

Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats.

PubMed

Lee, Yen-Mei; Cheng, Pao-Yun; Hong, Su-Fen; Chen, Shu-Ying; Lam, Kwok-Keung; Sheu, Joen-Rong; Yen, Mao-Hsiung

2005-07-01

Heme oxygenase-1 (HO-1), an inducible stress protein, has been implicated in cytoprotection against oxidative stress in vitro and in vivo. Estrogens also have antioxidant effects. This study investigated the time course of HO-1 and inducible nitric oxide synthase (iNOS) expression in the aortas of ovariectomized rats, and the regulatory relationship between the NO/NOS and the carbon monoxide/HO systems. HO-1 and iNOS protein expression was induced by ovariectomy (Ovx) and was extremely high 2-6 weeks after Ovx compared with the sham-operated group. Expression of the constitutive enzymes HO-2 and endothelial NOS did not differ significantly between sham-operated and Ovx rats. 17beta-Estradiol (E(2)) replacement reversed these changes in rats after Ovx. Long-term treatment with the antioxidant tempol significantly inhibited HO-1 and iNOS expression. The iNOS inhibitor aminoguanidine significantly suppressed the induction of HO-1. Oxidized glutathione in the hearts of Ovx rats increased gradually, with significant elevation at 3-6 weeks after Ovx compared with the sham-operated group, whereas plasma levels of NO metabolites were significantly reduced 4-6 weeks after Ovx. Treatment with the HO inhibitor zinc protoporphyrin IX blocked HO-1 induction, but significantly increased the plasma levels of NO metabolites. In conclusion, HO-1 is induced by oxidative stress resulting from E(2) depletion. The NO/iNOS system contributes to the induction of HO-1, which may subsequently suppress iNOS activity to modulate vasculoprotective effects after menopause.

Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury

PubMed Central

Zhang, Yi; Jiang, Ge; Sauler, Maor; Lee, Patty J.

2013-01-01

The lung endothelium is a major target for inflammatory and oxidative stress. Heme oxygenase-1 (HO-1) induction is a crucial defense mechanism during oxidant challenges, such as hyperoxia. The role of lung endothelial HO-1during hyperoxia in vivo is not well defined. We engineered lentiviral vectors with microRNA (miRNA) sequences controlled by vascular endothelium cadherin (VE-cad) to study the specific role of lung endothelial HO-1. Wild-type (WT) murine lung endothelial cells (MLECs) or WT mice were treated with lentivirus and exposed to hyperoxia (95% oxygen). We detected HO-1 knockdown (∼55%) specifically in the lung endothelium. MLECs and lungs showed approximately a 2-fold increase in apoptosis and ROS generation after HO-1 silencing. We also demonstrate for the first time that silencing endothelial HO-1 has the same effect on lung injury and survival as silencing HO-1 in multiple lung cell types and that HO-1 regulates caspase 3 activation and autophagy in endothelium during hyperoxia. These studies demonstrate the utility of endothelial-targeted gene silencing in vivo using lentiviral miRNA constructs to assess gene function and that endothelial HO-1 is an important determinant of survival during hyperoxia.—Zhang, Y., Jiang, G., Sauler, M., Lee, P. J. Lung endothelial HO-1 targeting in vivo using lentiviral miRNA regulates apoptosis and autophagy during oxidant injury. PMID:23771928

Enabling Design

DTIC Science & Technology

2009-05-21

Figure 1. Methodology in Hierarchical Context. 2 Peter Checkland , Systems Thinking, System...Joint Forces Command, 2008. Checkland , Peter. Systems Thinking, System Practice. Chichester: John Wiley & Sons, 1981. FM 6-0 Mission Command: Command

Uterine sarcoma

MedlinePlus

... Churchill Livingstone; 2014:chap 88. Crum CP, Laury AR, Hirsch MS, Quick CM, Peters WA. Undifferentiated uterine sarcoma. In: Crum CP, Quick CM, Laury AR, Peters WA, Hirsch MS, eds. Gynecologic and Obstetric ...

Conflicts of interest of editors of medical journals

PubMed Central

Minhajuddin, Abu

2018-01-01

Background Almost all medical journals now require authors to publicly disclose conflicts of interests (COI). The same standard and scrutiny is rarely employed for the editors of the journals although COI may affect editorial decisions. Methods We conducted a retrospective observational study to determine the prevalence and magnitude of financial relationships among editors of 60 influential US medical journals (10 each for internal medicine and five subspecialties: cardiology, gastroenterology, neurology, dermatology and allergy & immunology). Open Payments database was reviewed to determine the percentage of physician editors receiving payments and the nature and amount of these payments. Findings 703 unique physician editors were included in our analysis. 320/703 (46%) received 8659 general payments totaling $8,120,562. The median number of payments per editor was 9 (IQR 3–26) and the median amount per payment was $91 (IQR $21–441). The median total payment received by each editor in one year was $4,364 (IQR $319–23,143). 152 (48%) editors received payments more than $5,000 in a year, a threshold considered significant by the National Institutes of Health. COI policies for editors were available for 34/60 (57%) journals but only 7/34 (21%) publicly reported the disclosures and only 2 (3.%) reported the dollar amount received. Interpretation A significant number of editors of internal medicine and subspecialty medical journals have financial COI and very few are publicly disclosed. Specialty journal editors have more COI compared to general medicine journal editors. Current policies for disclosing COI for editors are inconsistent and do not comply with the recommended standards. PMID:29775468

New Editors Appointed for Sections of Journal of Geophysical Research

NASA Astrophysics Data System (ADS)

2009-04-01

New editors have been appointed for the Atmospheres, Biogeosciences, and Oceans sections of the Journal of Geophysical Research (JGR). Joost de Gouw (NOAA, Boulder, Colo.) and Renyi Zhang (Texas A&M, College Station) are filling the vacancies of retiring Atmospheres section editors John Austin and Jose Fuentes. De Gouw and Zhang join the continuing editors Steven Ghan and Yinon Rudich. Sara Pryor (Indiana University, Bloomington) is joining the Atmospheres section editorial board as an associate editor now; she will transition to editor in January 2010.

The effects of increased heme oxygenase-1 on the lymphoproliferative response in dogs with visceral leishmaniasis.

PubMed

Almeida, Breno Fernando Martins de; Silva, Kathlenn Liezbeth Oliveira; Chiku, Vanessa Marim; Leal, Aline Aparecida Correa; Venturin, Gabriela Lovizutto; Narciso, Luis Gustavo; Fink, Maria Fernanda Cereijido Bersni; Eugênio, Flavia de Rezende; Santos, Paulo Sergio Patto Dos; Ciarlini, Paulo Cesar; Lima, Valéria Marçal Felix de

2017-05-01

Canine visceral leishmaniasis (CVL) is known to affect the cellular immunity of infected dogs, through impairing lymphoproliferation and microbicidal mechanisms. This study examined heme oxygenase-1 (HO-1) and its metabolites, oxidative stress and IL-10 levels in CVL and investigated correlations between these parameters. Additionally, the effects of HO-1 inhibition on the lymphoproliferative response and cytokine production in lymph node cells (LNCs) from infected dogs were evaluated. Forty-four dogs, 24 controls and 20 dogs with CVL were selected. Plasma and splenic levels of HO-1, haptoglobin, soluble CD163 receptor, ferritin and IL-10 were determined using capture ELISA. The HO-1 levels and relative gene expression in peripheral blood and bone marrow mononuclear cells were also determined. LNCs proliferation was evaluated with an HO-1 activator and with an HO-1 inhibitor, in the presence of the Leishmania infantum soluble antigen (SAgL), using flow cytometry. HO-1, IL-2, IFN-gamma and IL-10 were also determined in these cultures using capture ELISA. Infected dogs presented oxidative stress and increased HO-1 levels and relative gene expression, with correlation between oxidative stress and HO-1. The substances from heme metabolism and IL-10 were also elevated in the plasma and spleens of infected dogs. IL-10 and HO-1 levels were positively correlated with one another. Inhibition of HO-1 increased LNCs proliferation and decreased IL-10 and IL-2 production in the presence of SAgL. The increased HO-1 metabolism observed in CVL is probably associated with oxidative stress and increased IL-10, which could be one of the mechanisms responsible for inhibition of the lymphoproliferative response in sick dogs. Copyright © 2016 Elsevier GmbH. All rights reserved.

Characterization of docosahexaenoic acid (DHA)-induced heme oxygenase-1 (HO-1) expression in human cancer cells: the importance of enhanced BTB and CNC homology 1 (Bach1) degradation.

PubMed

Wang, Shuai; Hannafon, Bethany N; Wolf, Roman F; Zhou, Jundong; Avery, Jori E; Wu, Jinchang; Lind, Stuart E; Ding, Wei-Qun

2014-05-01

The effect of docosahexaenoic acid (DHA) on heme oxygenase-1 (HO-1) expression in cancer cells has never been characterized. This study examines DHA-induced HO-1 expression in human cancer cell model systems. DHA enhanced HO-1 gene expression in a time- and concentration-dependent manner, with maximal induction at 21 h of treatment. This induction of HO-1 expression was confirmed in vivo using a xenograft nude mouse model fed a fish-oil-enriched diet. The increase in HO-1 gene transcription induced by DHA was significantly attenuated by the antioxidant N-acetyl cysteine, suggesting the involvement of oxidative stress. This was supported by direct measurement of lipid peroxide levels after DHA treatment. Using a human HO-1 gene promoter reporter construct, we identified two antioxidant response elements (AREs) that mediate the DHA-induced increase in HO-1 gene transcription. Knockdown of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression compromised the DHA-induced increase in HO-1 gene transcription, indicating the importance of the Nrf2 pathway in this event. However, the nuclear protein levels of Nrf2 remained unchanged upon DHA treatment. Further studies demonstrated that DHA reduces nuclear Bach1 protein expression by promoting its degradation and attenuates Bach1 binding to the AREs in the HO-1 gene promoter. In contrast, DHA enhanced Nrf2 binding to the AREs without affecting nuclear Nrf2 expression levels, indicating a new cellular mechanism that mediates DHA's induction of HO-1 gene transcription. To our knowledge, this is the first characterization of DHA-induced HO-1 expression in human malignant cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Haem oxygenase delays programmed cell death in wheat aleurone layers by modulation of hydrogen peroxide metabolism

PubMed Central

Wu, Mingzhu; Huang, Jingjing; Xu, Sheng; Ling, Tengfang; Xie, Yanjie; Shen, Wenbiao

2011-01-01

Haem oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced cell and tissue injury in animals and plants. In this report, it is confirmed that programmed cell death (PCD) in wheat aleurone layers is stimulated by GA and prevented by ABA. Meanwhile, HO activity and HO-1 protein expression exhibited lower levels in GA-treated layers, whereas the hydrogen peroxide (H2O2) content was apparently increased. The pharmacology approach illustrated that scavenging or accumulating H2O2 either delayed or accelerated GA-induced PCD. Furthermore, pretreatment with the HO-1 specific inhibitor, zinc protoporphyrin IX (ZnPPIX), before exposure to GA, not only decreased HO activity but also accelerated GA-induced PCD significantly. The application of the HO-1 inducer, haematin, and the enzymatic reaction product of HO, carbon monoxide (CO) aqueous solution, both of which brought about a noticeable induction of HO expression, substantially prevented GA-induced PCD. These effects were reversed when ZnPPIX was added, suggesting that HO in vivo played a role in delaying PCD. Meanwhile, catalase (CAT) and ascorbate peroxidase (APX) activities or transcripts were enhanced by haematin, CO, or bilirubin (BR), the catalytic by-product of HO. This enhancement resulted in a decrease in H2O2 production and a delay in PCD. In addition, the antioxidants butylated hydroxytoluene (BHT), dithiothreitol (DTT), and ascorbic acid (AsA) were able not only to delay PCD but also to mimic the effects of haematin and CO on HO up-regulation. Overall, the above results suggested that up-regulation of HO expression delays PCD through the down-regulation of H2O2 production. PMID:20797999

Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs

PubMed Central

Quan, Shuo; Yang, Liming; Abraham, Nader G.; Kappas, Attallah

2001-01-01

Our objective was to determine whether overexpression and underexpression of human heme oxygenase (HHO)-1 could be controlled on a long-term basis by introduction of the HO-1 gene in sense (S) and antisense (AS) orientation with an appropriate vector into endothelial cells. Retroviral vector (LXSN) containing viral long terminal repeat promoter-driven human HO-1 S (LSN-HHO-1) and LXSN vectors containing HHO-1 promoter (HOP)-controlled HHO-1 S and AS (LSN-HOP-HHO-1 and LSN-HOP-HHO-1-AS) sequences were constructed and used to transfect rat lung microvessel endothelial cells (RLMV cells) and human dermal microvessel endothelial cells (HMEC-1 cells). RLMV cells transduced with HHO-1 S expressed human HO-1 mRNA and HO-1 protein associated with elevation in total HO activity compared with nontransduced cells. Vector-mediated expression of HHO-1 S or AS under control of HOP resulted in effective production of HO-1 or blocked induction of endogenous human HO-1 in HMEC-1 cells, respectively. Overexpression of HO-1 AS was associated with a long-term decrease (45%) of endogenous HO-1 protein and an increase (167%) in unmetabolized exogenous heme in HMEC-1 cells. Carbon monoxide (CO) production in HO-1 S- or AS-transduced HMEC-1 cells after heme treatment was increased (159%) or decreased (50%), respectively, compared with nontransduced cells. HO-2 protein levels did not change. These findings demonstrate that HHO-1 S and AS retroviral constructs are functional in enhancing and reducing HO activity, respectively, and thus can be used to regulate cellular heme levels, the activity of heme-dependent enzymes, and the rate of heme catabolism to CO and bilirubin. PMID:11593038

Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs.

PubMed

Quan, S; Yang, L; Abraham, N G; Kappas, A

2001-10-09

Our objective was to determine whether overexpression and underexpression of human heme oxygenase (HHO)-1 could be controlled on a long-term basis by introduction of the HO-1 gene in sense (S) and antisense (AS) orientation with an appropriate vector into endothelial cells. Retroviral vector (LXSN) containing viral long terminal repeat promoter-driven human HO-1 S (LSN-HHO-1) and LXSN vectors containing HHO-1 promoter (HOP)-controlled HHO-1 S and AS (LSN-HOP-HHO-1 and LSN-HOP-HHO-1-AS) sequences were constructed and used to transfect rat lung microvessel endothelial cells (RLMV cells) and human dermal microvessel endothelial cells (HMEC-1 cells). RLMV cells transduced with HHO-1 S expressed human HO-1 mRNA and HO-1 protein associated with elevation in total HO activity compared with nontransduced cells. Vector-mediated expression of HHO-1 S or AS under control of HOP resulted in effective production of HO-1 or blocked induction of endogenous human HO-1 in HMEC-1 cells, respectively. Overexpression of HO-1 AS was associated with a long-term decrease (45%) of endogenous HO-1 protein and an increase (167%) in unmetabolized exogenous heme in HMEC-1 cells. Carbon monoxide (CO) production in HO-1 S- or AS-transduced HMEC-1 cells after heme treatment was increased (159%) or decreased (50%), respectively, compared with nontransduced cells. HO-2 protein levels did not change. These findings demonstrate that HHO-1 S and AS retroviral constructs are functional in enhancing and reducing HO activity, respectively, and thus can be used to regulate cellular heme levels, the activity of heme-dependent enzymes, and the rate of heme catabolism to CO and bilirubin.

Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein.

PubMed Central

Ewing, J F; Maines, M D

1991-01-01

Catalytic activity of heme oxygenase (heme, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.3) isozymes, HO-1 and HO-2, permits production of physiologic isomers of bile pigments. In turn, bile pigments biliverdin and bilirubin are effective antioxidants in biological systems. In the rat brain we have identified only the HO-1 isozyme of heme oxygenase as a heat shock protein and defined hyperthermia as a stimulus that causes an increase in brain HO-1 protein. Exposure of male rats to 42 degrees C for 20 min caused a rapid and marked increase in brain 1.8-kilobase HO-1 mRNA. Specifically, a 33-fold increase in brain HO-1 mRNA was observed within 1 h and sustained for at least 6 h posttreatment. In contrast, the two HO-2 homologous transcripts (1.3 and 1.9 kilobases) did not respond to heat shock; neither the ratio nor the level of the two messages differed from that of the control when measured either at 1, 6, or 24 h after hyperthermia. The induction of a 1.8-kilobase HO-1 mRNA resulted in a pronounced increase in HO-1 protein 6 h after hyperthermia, as detected by both Western immunoblot and RIA. Immunocytochemistry of rat brain showed discrete localization of HO-1-like protein only in neurons of select brain regions. Six hours after heat shock, an intense increase in HO-1-like protein was observed in both Purkinje cells of the cerebellum and epithelial cells lining the cerebral aqueduct of the brain. We suggest that the increase in HO-1 protein, hence increased capacity to form bile pigments, represents a neuronal defense mechanism against heat shock stress. Images PMID:2052613

Consistency of the Health of the Nation Outcome Scales (HoNOS) at inpatient-to-community transition.

PubMed

Luo, Wei; Harvey, Richard; Tran, Truyen; Phung, Dinh; Venkatesh, Svetha; Connor, Jason P

2016-04-27

The Health of the Nation Outcome Scales (HoNOS) are mandated outcome-measures in many mental-health jurisdictions. When HoNOS are used in different care settings, it is important to assess if setting specific bias exists. This article examines the consistency of HoNOS in a sample of psychiatric patients transitioned from acute inpatient care and community centres. A regional mental health service with both acute and community facilities. 111 psychiatric patients were transferred from inpatient care to community care from 2012 to 2014. Their HoNOS scores were extracted from a clinical database; Each inpatient-discharge assessment was followed by a community-intake assessment, with the median period between assessments being 4 days (range 0-14). Assessor experience and professional background were recorded. The difference of HoNOS at inpatient-discharge and community-intake were assessed with Pearson correlation, Cohen's κ and effect size. Inpatient-discharge HoNOS was on average lower than community-intake HoNOS. The average HoNOS was 8.05 at discharge (median 7, range 1-22), and 12.16 at intake (median 12, range 1-25), an average increase of 4.11 (SD 6.97). Pearson correlation between two total scores was 0.073 (95% CI -0.095 to 0.238) and Cohen's κ was 0.02 (95% CI -0.02 to 0.06). Differences did not appear to depend on assessor experience or professional background. Systematic change in the HoNOS occurs at inpatient-to-community transition. Some caution should be exercised in making direct comparisons between inpatient HoNOS and community HoNOS scores. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ureterocele

MedlinePlus

... ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 128. Peters CA, Mendelsohn C. Ectopic ureter, ureterocele, and ureteral anomalies. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

49 CFR 37.53 - Exception for New York and Philadelphia.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Eastern Paralyzed Veterans Association, Inc., James J. Peters, Terrance Moakley, and Denise Figueroa... between Eastern Paralyzed Veterans Association of Pennsylvania, Inc., and James J. Peters, individually...

From theory to field experiments

NASA Astrophysics Data System (ADS)

de Vos, Bram

2016-04-01

Peter Raats' achievements in Haren (NL) 1986-1997 were based on a solid theoretical insight in hydrology and transport process in soil. However, Peter was also the driving force behind many experimental studies and applied research. This will be illustrated by a broad range of examples ranging from the dynamics of composting processes of organic material; modelling and monitoring nutrient leaching at field-scale; wind erosion; water and nutrient dynamics in horticultural production systems; oxygen diffusion in soils; and processes of water and nutrient uptake by plant roots. Peter's leadership led to may new approaches and the introduction of innovative measurement techniques in Dutch research; ranging from TDR to nutrient concentration measurements in closed fertigation systems. This presentation will give a brief overview how Peter's theoretical and mathematical insights accelerated this applied research.

K istorii goroskopa Petra Velikogo %t On the history of horoscope of Peter the Great

NASA Astrophysics Data System (ADS)

Bronshtehn, V. A.

In the first part of the paper the question is discussed if Simeon Polotsky (1629-1680), poet and teacher of children of the Russian tsar Alexei Mikhailovich, was also the author of the horoscope of his son, in the future - Russian emperor Peter the Great, born in 1672. The poems by Simeon Polotsky with astrological contents are analyzed. The conclusion is supported that he could be the author of Peter the Great horoscope. In the second part a recently found text of the horoscope of Peter the Great reconstructed in 1775 by Russian astronomer Andrei Lexell of the request of historian G. F. Miller is published and discussed. It is also compared with texts previously published (in 1842) by Russian historians Pogodin and Polevoi.

Journal Editors Celebrated at Editors' Evening

NASA Astrophysics Data System (ADS)

Panning, Jeanette

2014-02-01

At the Fall Meeting, the premiere social event for AGU's many journal editors is the annual Editors' Evening, an opportunity for members to celebrate and to recognize the efforts of retiring editors. At the event, AGU president Carol Finn welcomed all those in attendance and thanked them for volunteering their time for the benefit of AGU and the wider research community.

Examining Editor-Author Ethics: Real-World Scenarios from Interviews with Three Journal Editors

ERIC Educational Resources Information Center

Amare, Nicole; Manning, Alan

2009-01-01

Those who submit manuscripts to academic journals may benefit from a better understanding of how editors weigh ethics in their interactions with authors. In an attempt to ascertain and to understand editors' ethics, we interviewed 3 current academic journal editors of technical and/or business communication journals. We asked them about the…

Clinical Applications of Wavefront Refraction

PubMed Central

Bruce, Adrian S.; Catania, Louis J.

2014-01-01

ABSTRACT Purpose To determine normative reference ranges for higher-order wavefront error (HO-WFE), compare these values with those in common ocular pathologies, and evaluate treatments. Methods A review of 17 major studies on HO-WFE was made, involving data for a total of 31,605 subjects. The upper limit of the 95% confidence interval (CI) for HO-WFE was calculated from the most comprehensive of these studies using normal healthy patients aged 20 to 80 years. There were no studies identified using the natural pupil size for subjects, and for this reason, the HO-WFE was tabulated for pupil diameters of 3 to 7 mm. Effects of keratoconus, pterygium, cataract, and dry eye on HO-WFE were reviewed and treatment efficacy was considered. Results The calculated upper limit of the 95% CI for HO-WFE in a healthy normal 35-year-old patient with a mesopic pupil diameter of 6 mm would be 0.471 μm (471 nm) root-mean-square or less. Although the normal HO-WFE increases with age for a given pupil size, it is not yet completely clear how the concurrent influence of age-related pupillary miosis affects these findings. Abnormal ocular conditions such as keratoconus can induce a large HO-WFE, often in excess of 3.0 μm, particularly attributed to coma. For pterygium or cortical cataract, a combination of coma and trefoil was more commonly induced. Nuclear cataract can induce a negative spherical HO-WFE, usually in excess of 1.0 μm. Conclusions The upper limit of the 95% CI for HO-WFE root-mean-square is about 0.5 μm with normal physiological pupil sizes. With ocular pathologies, HO-WFE can be in excess of 1.0 μm, although many devices and therapeutic and surgical treatments are reported to be highly effective at minimizing HO-WFE. More accurate normative reference ranges for HO-WFE will require future studies using the subjects’ natural pupil size. PMID:25216319

Upregulation of heme oxygenase-1 gene by turpentine oil-induced localized inflammation: involvement of interleukin-6.

PubMed

Tron, Kyrylo; Novosyadlyy, Ruslan; Dudas, Jozsef; Samoylenko, Anatoly; Kietzmann, Thomas; Ramadori, Giuliano

2005-03-01

Heme oxygenase-1 (HO-1) is the inducible isoform of an enzyme family responsible for heme degradation and was suggested to be involved in the acute phase response in the liver. However, the mechanisms of the HO-1 regulation under inflammatory conditions are poorly understood. Therefore, the purpose of the current work was to study the expression of HO-1 in the liver and other organs of rats with a localized inflammation after intramuscular injection of turpentine oil (TO). Since interleukin-6 (IL-6) is known to be a principal mediator of inflammation, the levels of this cytokine were also estimated in the animal model used. HO-1 and IL-6 expression was evaluated by Northern blot, in situ hybridization, Western blot, immunohistochemistry and enzyme-linked immunosorbent assay. In the liver and injured muscle, the HO-1 mRNA levels were dramatically increased 4-6 h after TO administration. HO-1 protein levels in the liver were elevated starting from 6-12 h after the treatment. In other internal organs such as the heart, kidney and large intestine, only a slight induction of HO-1 mRNA was observed. IL-6-specific transcripts appeared only in the injured muscle and were in accordance with serum levels of IL-6. In turn, temporal expression of IL-6 in the muscle and circulatory IL-6 levels correlated well with HO-1 expression in the liver and injured muscle. In the liver of control rats HO-1 protein was detected in Kupffer cells, while in TO-injected rats also hepatocytes became strongly HO-1 positive. Conversely, in the injured muscle, HO-1 immunoreactivity was attributed only to macrophages. Our data demonstrate that during localized inflammation HO-1 expression was rapidly and strongly induced in macrophages of injured muscle and in hepatocytes, and IL-6 derived from injured muscle seems to be responsible for the HO-1 induction in the liver.

Lipoxin A4-Induced Heme Oxygenase-1 Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury via p38 MAPK Activation and Nrf2/ARE Complex

PubMed Central

Chen, Xiao-Qing; Wu, Sheng-Hua; Zhou, Yu; Tang, Yan-Rong

2013-01-01

Objective To investigate whether lipoxin A4 (LXA4) increases expression of heme oxygenase-1(HO-1) in cardiomyocytes, whether LXA4-induced HO-1 protects cardiomyocytes against hypoxia/reoxygenation (H/R) injury, and what are the mechanisms involved in the LXA4-induced HO-1 induction. Methods Rat cardiomyocytes were exposed to H/R injury with or without preincubation with LXA4 or HO-1 inhibitor ZnPP-IX or various signal molecule inhibitors. Expressions of HO-1 protein and mRNA were analyzed by using Western blot and RT-PCR respectively. Activity of nuclear factor E2-related factor 2 (Nrf2) binding to the HO-1 E1 enhancer was assessed by chromatin immunoprecipitation. Nrf2 binding to the HO-1 antioxidant responsive element (ARE) were measured by using electrophoretic mobility shift assay. Results Pretreatment of the cells undergoing H/R lesion with LXA4 significantly reduced the lactate dehydrogenase and creatine kinase productions, increased the cell viability, and increased the expressions of HO-1 protein and mRNA and HO-1 promoter activity. HO-1 inhibition abolished the protective role of LXA4 on the cells undergoing H/R lesion. LXA4 increased p38 mitogen-activated protein kinase (p38 MAPK) activation, nuclear translocation of Nrf2, Nrf2 binding to the HO-1 ARE and E1 enhancer in cardiomyocytes with or without H/R exposure. Conclusion The protection role of LXA4 against H/R injury of cardiomyocytes is related to upregulation of HO-1, via activation of p38 MAPK pathway and nuclear translocation of Nrf2 and Nrf2 binding to the HO-1 ARE and E1 enhancer, but not via activation of phosphatidyinositol-3-kinase or extracellular signal-regulated kinase pathway. PMID:23826208

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Soon Won; Sohn, Eun Jeong; Kim, Dae Won

Highlights: {yields} Recombinant PEP-1 heme oxygenase-1 expression vector was constructed and overexpressed. {yields} We investigated transduction efficiency of PEP-1-HO-1 protein in Raw 264.7 cells. {yields} PEP-1-HO-1 was efficiently transduced into Raw 264.7 cells in a dose and time dependent manner. {yields} PEP-1-HO-1 exerted anti-inflammatory activity in Raw 264.7 cells and in a mice edema model. {yields} PEP-1-HO-1 could be used as a therapeutic drug against inflammatory diseases. -- Abstract: Heme oxygenase-1 (HO-1), which catalyzes the degradation of free heme to biliverdin, carbon monoxide (CO), and free iron (Fe{sup 2+}), is up-regulated by several cellular stress and cell injuries, including inflammation,more » ischemia and hypoxia. In this study, we examined whether fusion of HO-1 with PEP-1, a protein transduction domain that is able to deliver exogenous molecules to living cells or tissues, would facilitate HO-1 delivery to target cells and tissues, and thereby effectively exert a therapeutically useful response against inflammation. Western blot analysis demonstrated that PEP-1-HO-1 fusion proteins were transduced into Raw 264.7 cells in time- and dose-dependent manners, and were stably maintained in the cells for about 60 h. In addition, fluorescence analysis revealed that only PEP-1-HO-1 fusion proteins were significantly transduced into the cytoplasm of cells, while HO-1 proteins failed to be transduced. In lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse edema model, transduced PEP-1-HO-1 fusion proteins effectively inhibited the overexpression of pro-inflammatory mediators and cytokines. Also, histological analysis demonstrated that PEP-1-HO-1 remarkably suppressed ear edema. The results suggest that the PEP-1-HO-1 fusion protein can be used as a therapeutic molecule against reactive oxygen species-related inflammatory diseases.« less

Low heme oxygenase-1 levels in patients with systemic sclerosis are associated with an altered Toll-like receptor response: another role for CXCL4?

PubMed

van Bon, Lenny; Cossu, Marta; Scharstuhl, Alwin; Pennings, Bas W C; Vonk, Madelon C; Vreman, Hendrik J; Lafyatis, Robert L; van den Berg, Wim; Wagener, Frank A D T G; Radstake, Timothy R D J

2016-11-01

SSc is a disease characterized by inflammation and fibrosis. Heme Oxygenase-1 (HO-1) is a haem-degrading enzyme that mediates resolution of inflammation and is induced upon mediators abundantly present in SSc. We aimed to assess whether HO-1 expression/function is disturbed in SSc patients and could therefore be contributing to the ongoing inflammation. In total, 92 SSc patients and 48 healthy controls were included. By measuring total bilirubin in plasma in vivo, HO-activity was assessed. HO-1 expression levels were determined with western blot in monocytes before and after induction of HO-1 with cobalt protoporphyrin (CoPP) with or without CXCL4. Monocyte-derived dendritic cells (DCs) were stimulated with several Toll-like receptor (TLR) ligands with or without pre-stimulation with CoPP for 24 h. Cytokine levels were measured in the supernatants using the Luminex Bead Array. SSc patients have lower plasma levels of bilirubin, suggestive of an aberrant HO-1 function. We demonstrated low HO-1 expression in immune cells from SSc patients, whereas induction with CoPP was able to restore HO-1 levels in DCs from SSc patients, almost normalizing the increased TLR response observed in SSc. Co-exposure to CXCL4 completely abrogated CoPP-induced HO-1 expression, suggesting that the high CXCL4 levels present in SSc patients block the normal induction of HO-1 and its function. We demonstrate that HO activity in SSc patients is decreased and show its functional consequences. Since CXCL4 blocks the induction of HO-1 expression, neutralization of CXCL4 in SSc patients could have clinical benefits by diminishing overactivation of immune cells and other anti-inflammatory effects of HO-1. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Whole Brain Functional Connectivity Pattern Homogeneity Mapping.

PubMed

Wang, Lijie; Xu, Jinping; Wang, Chao; Wang, Jiaojian

2018-01-01

Mounting studies have demonstrated that brain functions are determined by its external functional connectivity patterns. However, how to characterize the voxel-wise similarity of whole brain functional connectivity pattern is still largely unknown. In this study, we introduced a new method called functional connectivity homogeneity (FcHo) to delineate the voxel-wise similarity of whole brain functional connectivity patterns. FcHo was defined by measuring the whole brain functional connectivity patterns similarity of a given voxel with its nearest 26 neighbors using Kendall's coefficient concordance (KCC). The robustness of this method was tested in four independent datasets selected from a large repository of MRI. Furthermore, FcHo mapping results were further validated using the nearest 18 and six neighbors and intra-subject reproducibility with each subject scanned two times. We also compared FcHo distribution patterns with local regional homogeneity (ReHo) to identify the similarity and differences of the two methods. Finally, FcHo method was used to identify the differences of whole brain functional connectivity patterns between professional Chinese chess players and novices to test its application. FcHo mapping consistently revealed that the high FcHo was mainly distributed in association cortex including parietal lobe, frontal lobe, occipital lobe and default mode network (DMN) related areas, whereas the low FcHo was mainly found in unimodal cortex including primary visual cortex, sensorimotor cortex, paracentral lobule and supplementary motor area. These results were further supported by analyses of the nearest 18 and six neighbors and intra-subject similarity. Moreover, FcHo showed both similar and different whole brain distribution patterns compared to ReHo. Finally, we demonstrated that FcHo can effectively identify the whole brain functional connectivity pattern differences between professional Chinese chess players and novices. Our findings indicated that FcHo is a reliable method to delineate the whole brain functional connectivity pattern similarity and may provide a new way to study the functional organization and to reveal neuropathological basis for brain disorders.

Heme oxygenase-1 protects endothelial cells from the toxicity of air pollutant chemicals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lawal, Akeem O.; Zhang, Min; Dittmar, Michael

Diesel exhaust particles (DEPs) are a major component of diesel emissions, responsible for a large portion of their toxicity. In this study, we examined the toxic effects of DEPs on endothelial cells and the role of DEP-induced heme oxygenase-1 (HO-1) expression. Human microvascular endothelial cells (HMECs) were treated with an organic extract of DEPs from an automobile engine (A-DEP) or a forklift engine (F-DEP) for 1 and 4 h. ROS generation, cell viability, lactate dehydrogenase leakage, expression of HO-1, inflammatory genes, cell adhesion molecules and unfolded protein respone (UPR) gene were assessed. HO-1 expression and/or activity were inhibited by siRNAmore » or tin protoporphyrin (Sn PPIX) and enhanced by an expression plasmid or cobalt protoporphyrin (CoPPIX). Exposure to 25 μg/ml of A-DEP and F-DEP significantly induced ROS production, cellular toxicity and greater levels of inflammatory and cellular adhesion molecules but to a different degree. Inhibition of HO-1 enzymatic activity with SnPPIX and silencing of the HO-1 gene by siRNA enhanced DEP-induced ROS production, further decreased cell viability and increased expression of inflammatory and cell adhesion molecules. On the other hand, overexpression of the HO-1 gene by a pcDNA 3.1D/V5-HO-1 plasmid significantly mitigated ROS production, increased cell survival and decreased the expression of inflammatory genes. HO-1 expression protected HMECs from DEP-induced prooxidative and proinflammatory effects. Modulation of HO-1 expression could potentially serve as a therapeutic target in an attempt to inhibit the cardiovascular effects of ambient PM. - Highlights: • We examined the role of HO-1 expression on diesel exhaust particle (DEP) in endothelial cells. • DEPs exert cytotoxic and inflammatory effects on human microvascular endothelial cells (HMECs). • DEPs induce HO-1 expression in HMECs. • HO-1 protects against the oxidative stress induced by DEps. • HO-1 attenuates the proinflammatory effects induced by DEPs.« less

FOREWORD: Peter Clay Eklund: a scientific biography Peter Clay Eklund: a scientific biography

NASA Astrophysics Data System (ADS)

Cole, Milton W.; Crespi, Vincent H.; Dresselhaus, Gene F.; Dresselhaus, Mildred S.; Mahan, Gerald D.; Sofo, Jorge O.

2010-08-01

Peter Eklund grew up in Southern California and attended the University of California at Berkeley, majoring in physics. After working for one year at the Lockheed Missile and Space Company in Sunnyvale, California, he left to pursue graduate studies at Purdue University. There he carried out PhD research in strongly correlated electron and phonon systems under the supervision of J M Honig and L L van Zandt. Peter joined the group of Millie and Gene Dresselhaus at MIT in 1974 as a Postdoctoral Fellow after one year as an instructor at the University of Kentucky. At MIT, he continued work on strongly correlated systems in collaboration with Professor David Adler (who had an adjoining office), but for the most part he got excited about sp2 carbon systems and graphite intercalation compounds, a new research direction which the Dresselhaus group had started one year before Peter's arrival at MIT. Over the next 35 years Peter, Millie and Gene co-authored over 50 research articles, several review articles, and a big nine-hundred-and-fifty page book. In 1974, they saw graphite intercalation compounds as a long-neglected research direction of great promise. They studied these new materials together over the next 16 years, focusing on their optical spectroscopy. Their pioneering vibrational spectroscopy studies provided a means to characterize the fundamental properties of carbon materials. Optical spectroscopy became a centerpiece in the research portfolios of all three, both when they were together at MIT and after Peter left for the University of Kentucky in 1977 to start his independent career as an Assistant Professor of Physics. Peter became a full Professor at Kentucky in 1986. He continued to work with Millie and Gene and also acquired an ever-expanding network of students, postdocs and collaborators. As each new carbon nanostructure emerged—graphite intercalation compounds, fullerenes, carbon nanotubes, and most recently graphene—Peter was at the cutting edge, leading the charge forward. His work on fullerenes, starting around 1988, culminated in a book co-authored with Millie and Gene in 1996, The Science of Fullerenes and Carbon Nanotubes [1]. Through careful sample handling and analysis, his group at Kentucky discovered the mechanism of photo-polymerization in fullerenes. In 2000, Peter co-edited the research monograph Fullerene Polymers and Fullerene Polymer Composites with A M Rao, a former student [2]. His group at Kentucky also performed the first definitive Raman study of the phonons responsible for superconductivity in alkali-doped fullerene compounds. Peter was awarded the prestigious University of Kentucky Research Professorship for his contributions to graduate education and research discoveries in carbon materials. In the summer of 1991, Peter held early discussions with his two long-time collaborators on the possibility of carbon nanotubes. These discussions inspired a talk by Millie at a fullerene workshop the next day concerning the possible existence of single-walled carbon nanotubes [3]. The first papers by Iijima on the synthesis of multiwalled nanotubes appeared soon thereafter [4]. In 1994, Peter measured an early Raman spectrum on a sample containing just 1% of single-walled tubes. On the basis of this early work, he convinced Rick Smalley to provide him with a proper sample of single-walled carbon nanotubes in 1996; this is the sample on which the highly cited single-walled carbon nanotube Raman spectrum was taken [5]. Carbon nanotubes then became a central focus of the Eklund group. Peter, Millie and Gene worked together on many aspects of carbon nanotubes, including the study of infrared-active modes, Raman active modes, Raman spectra for single-walled nanotubes, and the differences in the Raman spectra of semiconducting and metallic tubes. In 2009 they combined efforts to investigate phonons in graphene. Peter was also an entrepreneur. He started a company, CarboLex, to make and sell nanotubes in large quantities, thereby giving industrial support to advancing fundamental science. He co-founded two additional companies: PhotoStealth produced computer-generated camouflage patterns printed on textiles and ICMR pursued laser-driven synthesis of nanoparticles and coatings. ICMR moved from Lexington to Silicon Valley and evolved into Nanogram, later reorganized as NeoPhotonics. Both CarboLex and NeoPhotonics are still actively engaged in the research and development of nano-materials. Peter joined the Physics Department at Penn State University in 1999, becoming a Distinguished Professor in 2008. In 2002, he also joined the faculty of the Department of Materials Science and Engineering. In addition to further seminal work on carbon materials, Peter initiated a research effort in semiconducting nanowires, obtaining the first clear evidence of phonon confinement in 1D nanostructures. After the Novoselov-Geim work on monolayer graphene appeared, once again Peter Eklund was there to publish very early Raman spectra on monolayer, bilayer and few-layer graphene. Thus, the work of Peter Eklund unfolds the leading wave of discoveries in carbon nanostructures starting in 1974 and continuing over a thirty-five year period to August 2009. Peter mentored more than 40 graduate students and postdoctoral fellows. He co-authored over 300 research articles and more than 20 chapters in monographs. His scientific oeuvre has been cited more than 16 000 times. Peter acquired three US patents with five more pending. He was recognized with the Japan Carbon Award (2008), the American Carbon Society Graffin Award (2005), American Physical Society Fellowship (1990), and visiting/honorary professorships in Nankai University, Yokohama City University, Shinshu University, Tokyo Science University, and (as a visiting scientist) in the Solid State Division of Oak Ridge National Laboratory. From 2003 to 2006 he was a member of the Solid State Sciences Committee of the US National Academy of Sciences. Peter enjoyed challenges. He was in his glory while interpreting the stories told by experimental data in partnership with his colleagues and research team of dedicated postdocs and students. Peter was admired all over the world for his creativity, his kindness, his engaging personality, his breadth of interests, his sensitive character and his quick wit. Several friends have shared their memories: Kumble Subbaswamy (University of Kentucky, USA): 'Peter, along with Karen, were the gentlest and most generous souls I have ever met. He picked up stray dogs and stray graduate students alike, nurturing them through sickness and health. I will never forget the hospice-like care he provided to one international student who worked in his lab, but succumbed to cancer. In his early days at Kentucky, when funds to support his research were very scarce, he made frequent visits to the military surplus store nearby and behaved like a kid in a candy store, bringing back all sorts of electrical and mechanical parts for his experiments. It is in no small measure due to this ability that he built such a successful career. Peter was without peer when it came to instrument design and fabrication. I mentioned to him, during my job interview at the University of Kentucky (where he arrived one year before me), my interest in studying the Raman spectra of molten alkali halides. Several months later when I arrived on campus, I was surprised to find he had constructed a beautifully crafted Raman chamber supporting a contactless molten sample! He had anticipated and addressed every possible complication.' Qihua Xiong (Nanyang Technical University, Singapore): 'Peter was a great mentor; he knew how to stimulate students to explore their full potential. Students could knock on his door with questions or with new data any time. He was always patient. He explained physics with his fountain pen on a notepad or with a marker on a white board until students understood. When students made mistakes, he never blamed the student, because he believed it is part of training to allow students to make mistakes. I once designed a mask adapter to connect our existing three-inch photomasks to Srinivas's four-inch mask aligner. The design looked beautiful and the machine shop did a perfect job to machine and polish the piece. Unfortunately, I made a stupid mistake. The central opening was slightly larger than the square vacuum groves behind the mask holder and as a result, it leaked! I was very disappointed in myself, as I not only wasted grant money but also delayed our experiment. Peter patted my shoulder, picked up a sharpie and wrote on the mask adapter, 'even great people make mistakes, but they learn.' So we machined another one, and it worked well. This failure piece still stands on my bookshelf. I keep it as a motto: it warns me not to make any mistakes like that, but more importantly it encourages me to be a supervisor like Peter.' Joe Brill (University of Kentucky, USA): 'Peter's occasional impetuousness and his love of physics are illustrated by the following anecdote. In December, 1979, I had just joined the faculty at the University of Kentucky, excited about the prospect of collaborating with Peter, who had arrived two years before. I was, therefore, dumbfounded when Peter abruptly announced his resignation to join IBM to do research on printer ink. After less than two days at IBM, however, he sheepishly asked to come back to the UK, explaining that he couldn't enjoy doing research that didn't involve 'h-bar'. His UK colleagues, who had not even had the chance to raid his lab, of course agreed with great amusement and relief. His joy and enthusiasm for physics remained contagious and unforgettable.' Milton Cole (Penn State University, USA): 'Somehow my very last conversation with Peter, two days before his death, typified the hundreds of conversations we had about science, or even philosophy. His first words after greeting me consisted of a hypothetical explanation of the physical mechanism of a new intravenous tube he was obliged to use. He conveyed on that occasion the very same excitement that he displayed years earlier when he volunteered to present a demonstration of electrical circuitry to a group of third-grade students. Those eight-year olds became as enthusiastic as Peter. It is no wonder that Peter was so admired and loved.' Jackie Bortiatynski (Penn State University, USA): 'I loved working with Peter on summer science camps for kids. He was creative, funny, brilliant, and an inspiration. I just don't know where he got all his energy. I will truly miss him as a colleague.' Toshiaki Enoki (Tokyo Institute of Technology, Japan): 'Peter was very serious in his research work, but he also had an amiable personality with a very good sense of humour. I remember the occasion of a small international workshop, which was chaired by me in Ise, Japan in 1985. We had serious and intensive discussions in the scientific session, then in the evening we enjoyed an excursion and banquet in Ise, a small old town with a famous shrine named Ise Jingu. Peter romped out with joy wearing yukata (Japanese traditional night clothes) after taking a hot spring.' Robert Haddon (University of California, Riverside, USA): 'Peter was the driving force in creating a position for me at the University of Kentucky in 1997. After I joined Kentucky, we immediately focused on the large-scale synthesis of single-walled carbon nanotubes and we became one of a handful of research groups that could produce single-walled nanotubes in quantity. Soon after, we founded CarboLex and the university was awarded an NSF MRSEC on Advanced Carbon Materials. For most of the time that I spent at Kentucky, our research groups met as a unit and our collaboration greatly assisted me in making the transition to academia. Above all, Peter was a physicist in very much the same tradition as the great colleagues that I had been privileged to work with at the Bell Labs. Peter and Karen made me welcome in their home from the time I arrived in Lexington and I have fond memories of the time we spent together.' Photo Keith Williams (University of Virginia, USA): 'In 1993, Peter introduced me, in the dark, to his postdoc Apparao Rao, who was then doing Raman on C60 at Kentucky. I thought it was pretty interesting and that was how I began working for Peter. I was an exile from high-energy physics: the SSC had just been canceled and I had drifted in and out of biophysics and AMO and finally settled on Peter's brand of experimental nanomaterials physics. I immediately enjoyed Peter's ingenuity and his wonderful sense of humour. One aspect of Peter's character not widely appreciated by his students was his thrift: if something could be made, borrowed (with or without consent), or used after-hours then he always advocated that strongly. More than once, we got demo equipment, ran an all-nighter on it to collect data and then sent it back a day later. Almost nothing was bought off the shelf! Peter attributed these tendencies to his ancestry, and that was an unending joke between us. Of course, the strategy of making every penny count benefited me greatly in the long run, and last year I told him I had outdone him in my lab: almost everything was built from scratch, and everything else was on loan. He smiled a proud smile. On the personal side, however, Peter was always very generous; I fondly recall the dinners with him and Karen and the other students, their beloved dogs, with the Beach Boys inevitably playing in the background. Peter and Karen were wonderful to me and so many other students, and it didn't surprise me at all to learn that Peter's last scientific concern was that a proposal had been funded and that his students were going to be okay.' Kenichi Kojima (Yokohama City University, Japan): 'In 1997, Peter came to Yokohama as a Guest Professor at Yokohama City University to give his lectures to our graduate students. Peter was an excellent lecturer, of course. But when I played tennis with him for the first time, I found that he was an amazing tennis player as well. He hit the ball really hard, and his serves were amazingly fast. During his stay, Peter liked stopping over at a typical traditional Japanese-style pub for dinner by himself. One day he wanted to have a beer before dinner. However, he was not sure how to order draft beer in Japanese, and the manager of the pub did not understand English. He carefully listened to what the customers around him said when they ordered beer. He then said in a loud voice, 'Please give me a glass of mama beer.' In Japan, female servers in pubs are often called 'mama' by customers, and we call draft beer 'nama beer' because 'nama' means 'living' in Japanese. Probably 'nama' sounded like 'mama' to Peter. Later he proudly told me, with a happy smile, how he got a delicious draft Kirin beer. Peter loved not only science but also traditional Japanese culture. He was a polished person. I would like to show you the words written in his own hand in my visitor's book when he came to my home after playing tennis in 1997. May his soul rest in peace!' Photo Millie Dresselhaus (Massachusetts Institute of Technology, USA): 'At the time of Peter's entry into the study of sp2 carbons in 1974, the field was an eclectic area of science that only interested a small group of aficionados. Through his many contributions during the next 35 years as well as those of others, the field has grown dramatically, and now it is a major area of interest in condensed matter and materials physics worldwide. Working on joint projects together with Peter Eklund was both educational and enjoyable. In our joint efforts, I was responsible for the big picture, Peter was the master of experimental details and Gene Dresselhaus was the man responsible for getting things done well and on time. During the last 35 years of his life, starting from his postdoctoral period, we enjoyed a close working relation, especially for the first 25 of these years, overlapping with his stay at the University of Kentucky. As his career developed, our relationship changed from a postdoctoral advisor, to a collaborator, friend, and confidant. After his mother passed away I assumed the role of his 'second mother' as he called me. We remained very close personally, even though far away in location and despite his many other professional collaborators. Looking to the future, life without Peter will never be the same.' References [1] Dresselhaus M S, Dresselhaus G, and Eklund P C 1996 Science of Fullerenes and Carbon Nanotubes (New York: Academic Press) [2] Eklund P C and Rao A M 1999 Fullerene Polymers and Fullerene-Polymer Composites (Springer Series in Materials Science vol 38) (Berlin: Springer) [3] Dresselhaus M S 1991 Recent advances in electronic materials Proc. of the 38th Sagamore Army Mater. Res. Conf. (Watertown, MA, Materials Technology Laboratory) ed Thomas V Hynes p 45 [4] Iijima S 1991 Helical microtubules of graphitic carbon Nature 354 56-8 [5] Rao A M, Richter E, Bandow S, Chase B, Eklund P C, Williams K W, Fang S, Subbaswamy K R, Menon M, Thess A, Smalley R E, Dresselhaus G and Dresselhaus M S 1997 Diameter-selective Raman scattering from vibrational modes in carbon nanotubes Science 275 187-91

1.88 Micrometers InGaAsP Pumped, Room Temperature Ho: LuAG Laser

NASA Technical Reports Server (NTRS)

Barnes, Norman P.; Amzajerdian, Farzin; Reichle, Donald J.; Busch, George; Leisher, Paul

2009-01-01

A room temperature, directly diode pumped Ho:LuAG laser oscillated for the first time. Direct pumping of the Ho upper laser manifold maximizes efficiency, minimizes heating, and eliminates Ho:Tm energy sharing. Design and performance are presented.

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage

PubMed Central

Wang, Jian; Doré, Sylvain

2008-01-01

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1−/−) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1−/− mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states. PMID:17525142

Adenovirus-mediated heme oxygenase-1 gene transfer into rabbit ocular tissues.

PubMed

Abraham, N G; da Silva, J L; Lavrovsky, Y; Stoltz, R A; Kappas, A; Dunn, M W; Schwartzman, M L

1995-10-01

Heme oxygenase-1 (HO-1) is a stress protein induced up to 100-fold within a few hours after exposure to oxidative stress, and it has been shown to counteract oxidative injury induced by ultraviolet light or free radicals. The current study was undertaken to determine whether the HO-1 gene can be introduced into adult rabbit ocular tissues by microinjection of a recombinant replication-deficient adenovirus human HO-1 cDNA (Adv-HHO). Human HO-1 gene was used for transfection studies to differentiate endogenous from transfected HO. The purified Adv-HHO construct (10(8) pfu/ml) was mixed with lipofectamine and microinjected into the anterior chamber, vitreous cavity, and subretinal space of New Zealand rabbit eyes. After 2 weeks, total RNA was extracted from different ocular tissues, reverse transcription-polymerase chain reaction was performed using specific human HO-1 primers, and amplification products were subjected to Southern hybridization. Transfection with the Adv-HHO construct into rabbit corneal epithelial cells in culture resulted in a functional expression of the human HO-1 gene; the human HO-1 mRNA was detected, and enzyme activity increased threefold. Human HO-1 mRNA was detected in the retina after microinjection of the Adv-HHO construct into the subretinal space. Microinjection into the vitreous resulted in HO-1 mRNA expression in the corneal endothelium, iris, lens, and retina; after intracameral injection of the Adv-HHO construct, human HO-1 mRNA was detected in corneal epithelium and endothelium, ciliary body, lens, and iris. Regardless of the injection site, transfected human HO-1 mRNA was undetectable in tissues outside the eye, that is, brain, liver, and kidney. These results demonstrated a tissue-selective functional transfer of the human HO-1 gene into rabbit ocular tissues in vivo. This technique may be a promising means for delivering HO-1 gene in vivo as a protective mechanism against oxidative stress that contributes to the pathogenesis of ocular diseases such as cataract, light-induced injury, age-related macular degeneration, and diabetic retinopathy.

Preliminary dosimetric evaluation of (166)Ho-TTHMP for human based on biodistribution data in rats.

PubMed

Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza; Tajik, Mojtaba; Ghannadi-Maragheh, Mohammad

2014-12-01

In this work, the absorbed dose to each organ of human for (166)Ho-TTHMP was evaluated based on biodistribution studies in rats by a RADAR method and was compared with (166)Ho-DOTMP as the only clinically used Ho-166 bone marrow ablative agent. The highest absorbed dose for this complex is observed in red marrow with 0.922mGy/MBq. The results show that (166)Ho-TTHMP has considerable characteristics compared to (166)Ho-DOTMP and can be a good candidate for bone marrow ablation in patients with multiple myeloma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Radical loss in the atmosphere from Cu-Fe redox coupling in aerosols

NASA Astrophysics Data System (ADS)

Mao, J.; Fan, S.; Jacob, D. J.; Travis, K.; Naik, V.; Horowitz, L. W.

2012-12-01

The hydroperoxyl radical (HO2) is a major precursor of OH and tropospheric ozone. OH is the main atmospheric oxidant, while tropospheric ozone is an important surface pollutant and greenhouse gas. Standard gas-phase models for atmospheric chemistry tend to overestimate observed HO2 concentrations, and this has been tentatively attributed to heterogeneous uptake by aerosol particles. It is generally assumed that HO2 uptake by aerosol involves conversion to H2O2, but this is of limited efficacy as an HO2 sink because H2O2 can photolyze to regenerate OH and from there HO2. Joint atmospheric observations of HO2 and H2O2 suggest that HO2 uptake by aerosols may in fact not produce H2O2. Here we propose a catalytic mechanism involving coupling of the transition metal ions (TMI) Cu(I)/Cu(II) and Fe(II)/Fe(III) to rapidly convert HO2 to H2O in aerosols. The implied HO2 uptake significantly affects global model predictions of tropospheric OH, ozone, and other species, improving comparisons to observations, and may have a major and previously unrecognized impact on atmospheric oxidant chemistry.

HO-1-mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues.

PubMed

Zukor, Hillel; Song, Wei; Liberman, Adrienne; Mui, Jeannie; Vali, Hojatollah; Fillebeen, Carine; Pantopoulos, Kostas; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Schipper, Hyman M

2009-05-01

Oxidative stress, deposition of non-transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase-1 (HO-1) is up-regulated in AD and PD brain and promotes the accumulation of non-transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO-1 over-expression on astroglial mitochondrial morphology in vitro, (ii) the topography of aberrant iron sequestration in astrocytes over-expressing HO-1, and (iii) the role of iron regulatory proteins (IRP) in HO-1-mediated iron deposition. Astroglial hHO-1 over-expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO-1 promoted trapping of redox-active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO-1 activity promotes mitochondrial macroautophagy and sequestration of redox-active iron in astroglia independently of classical iron mobilization pathways. Glial HO-1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.

Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit

Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner.more » siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H{sub 2}O{sub 2}) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H{sub 2}O{sub 2} levels. Furthermore, H{sub 2}O{sub 2} independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H{sub 2}O{sub 2} levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H{sub 2}O{sub 2}-independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H{sub 2}O{sub 2} - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments omeprazole-mediated induction of HO-1.« less

PEOPLE IN PHYSICS: Interview with Peter Higgs

NASA Astrophysics Data System (ADS)

Fancey, Conducted by Norman

1998-01-01

Peter Higgs, FRSE, FRS held until recently a personal chair in theoretical physics at the University of Edinburgh and is now an emeritus professor. Peter is well known for predicting the existence of a new particle, the Higgs boson - as yet unconfirmed. He has been awarded a number of prizes in recognition of his work, most recently the Paul Dirac Medal and Prize for outstanding contributions to theoretical physics from the Institute of Physics and the 1997 High Energy and Particle Physics Prize by the European Physical Society.

The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents.

PubMed

Furuichi, Masayuki; Yokozuka, Motoi; Takemori, Ken; Yamanashi, Yoshitaka; Sakamoto, Atsuhiro

2009-08-01

The production of nitric oxide (NO) by inducible NO synthase (NOS) and carbon monoxide (CO) by inducible heme oxygenase (HO) contributes greatly to endotoxemia. Reciprocal relationships have been proposed between the NO/NOS and CO/HO systems. However, the interaction between these systems during endotoxemia is unclear, and it is unknown whether the interactive behavior differs among organs. Using endotoxic rats, we studied the effects of the inducible NOS (iNOS) inhibitor L-canavanine (CAN), and the HO inhibitor zinc protoporphyrin (ZPP) on gene expression and protein levels of iNOS, endothelial NOS (eNOS), inducible HO (HO-1), and constitutive HO (HO-2) in the brain, lung, heart, liver and kidney tissue. Intravenous injection of LPS significantly increased iNOS and HO-1 gene expression in all organs. The effects of LPS on eNOS gene expression differed among organs, with increased expression in the liver and kidney, and no change in the lung, brain and heart. ZPP administration down-regulated the LPS-induced increase in HO-1 expression and produced a further increase in iNOS expression in all organs. These data suggest that the CO/HO system modifies the NO/NOS system in endotoxic organs, and that there were only minor organ-specific behaviors in terms of the relationship between these systems in the organs examined.

Pivotal Advance: Heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity.

PubMed

Biburger, Markus; Theiner, Gabi; Schädle, Mirjam; Schuler, Gerold; Tiegs, Gisa

2010-02-01

HO-1 is the only inducible one of three isoenzymes that catalyzes the oxidative degradation of heme. HO-1 is inducible by various cellular stress factors and exerts cytoprotective and immunomodulatory effects. Recent publications demonstrated that HO-1 is constitutively expressed by CD4(+)CD25(+) T(regs) and induced in CD4(+)CD25(-) T cells upon FoxP3 transfection. Here, we investigated whether HO-1 was essential and sufficient for human T(regs) to exert immunosuppression in vitro. PGJ(2) induced pronounced expression of HO-1 in CD4(+)CD25(-) T cells without accompanying FoxP3 induction. Treatment of CD4(+)CD25(-) T cells with PGJ(2) decreased their proliferation, whereas the HO-1 inhibitor SnPP enhanced the proliferation of HO-1-expressing T(regs), suggesting that HO-1 may modulate the proliferative capacity of T lymphocytes. HO-1 modulation by SnPP treatment of T(regs) or PGJ(2) treatment of CD4(+)CD25(-) T cells neither suppressed nor induced immune-modulatory function in these cells, respectively, as measured by responder-cell proliferation and/or IL-2 production. In summary, these data suggest that HO-1 expression by T(regs) might contribute to their typical reluctance to proliferate but does not account independently for their suppressive functions.

[hHO-1 structure prediction and its mutant construct, expression, purification and activity analysis].

PubMed

Xia, Zhen Wei; Cui, Wen Jun; Zhou, Wen Pu; Zhang, Xue Hong; Shen, Qing Xiang; Li, Yun Zhu; Yu, Shan Chang

2004-10-01

Human Heme Oxygenase-1 (hHO-1) is the rate-limiting enzyme in the catabolism reaction of heme, which directly regulates the concentration of bilirubin in human body. The mutant structure was simulated by Swiss-pdbviewer procedure, which showed that the structure of active pocket was changed distinctly after Ala25 substituted for His25 in active domain, but the mutated enzyme still binded with heme. On the basis of the results, the expression vectors, pBHO-1 and pBHO-1(M), were constructed, induced by IPTG and expressed in E. coli DH5alpha strain. The expression products were purified with 30%-60% saturation (NH4)2SO4 and Q-Sepharose Fast Flow column chromatography. The concentration of hHO-1 in 30%-60% saturation (NH4)2SO4 components and in fractions through twice column chromatography was 3.6-fold and 30-fold higher than that in initial product, respectively. The activity of wild hHO-1 (whHO-1) and mutant hHO-1 (deltahHO-1) showed that the activity of deltahHO-1 was reduced 91.21% compared with that of whHO-1. The study shows that His25 is of importance for the mechanism of hHO-1, and provides the possibility for effectively regulating the activity to exert biological function.

Cystometric study

MedlinePlus

... dysfunction. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology. 11th ed. Philadelphia, ... children. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology. 11th ed. Philadelphia, ...

Uterine prolapse

MedlinePlus

... devices. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... prolapse. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

27 CFR 9.107 - Lodi.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (Photorevised 1987); (3) Peters, CA 1952 (Photorevised 1968); (4) Stockton East, Calif. 1968 (Photorevised 1987... through the Peters, CA map, and ending on the Stockton East, Calif. map); (3) Then proceed north along...

Penis pain

MedlinePlus

... Priapism. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... disease. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Elimination patterns

MedlinePlus

... urethra. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... disorders. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Genital sores - male

MedlinePlus

... genitalia. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... 26042815 . Review Date 8/26/2017 Updated by: Peter J Chen, MD, FACOG, Associate Professor of OBGYN ...

Retrograde ejaculation

MedlinePlus

... ejaculation. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... infertility. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Bioaccumulation of hydroxylated polychlorinated biphenyls and pentachlorophenol in the serum of northern elephant seal pups (Mirounga angustirostris)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louis, Caroline, E-mail: caroline.louis@uclouvain.be; Covaci, Adrian; Stas, Marie

Northern elephant seals (NES) (Mirounga angustirostris) from the Año Nuevo State Reserve (CA, USA) were sampled at 1-, 4-, 7- and 10-week post-weaning. Concentrations of hydroxylated polychlorinated biphenyls (HO-PCBs) and their parent PCBs were measured in the serum of each individual. The ΣHO-PCB concentrations in the serum increased significantly between early and late fast (from 282±20 to 529±31 pg/mL). This increase might result from a mobilisation of HO-PCBs transferred from the mother during gestation and/or lactation and stored in the pup's liver. Food deprivation has been shown to exacerbate biotransformation capacities in mammals, birds and fish. The HO-penta-CBs was themore » predominant homologue group, followed by HO-hexa-CBs and HO-hepta-CBs. No preferential pathway for the metabolism of HO-PCBs (HO-direct insertion or NIH-shift of a chlorine atom) could be evidenced. The concentrations of pentachlorophenol (PCP) in the serum of weaned NES increased from 103±7 pg/mL at early fast to 246±41 pg/mL at late fast, which is within the range of PCP concentrations usually encountered in marine mammals. - Highlights: • Σ HO-PCB concentrations in serum significantly increased between early and late fast. • The HO-penta-CBs were the predominant homologue group measured in serum. • No preferential pathway for the metabolism of HO-PCBs could be evidenced. • PCP concentrations in serum significantly increased between early and late fast.« less

Activation of AMPK stimulates heme oxygenase-1 gene expression and human endothelial cell survival

PubMed Central

Liu, Xiao-ming; Peyton, Kelly J.; Shebib, Ahmad R.; Wang, Hong; Korthuis, Ronald J.

2011-01-01

The present study determined whether AMP-activated protein kinase (AMPK) regulates heme oxygenase (HO)-1 gene expression in endothelial cells (ECs) and if HO-1 contributes to the biological actions of this kinase. Treatment of human ECs with the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) stimulated a concentration- and time-dependent increase in HO-1 protein and mRNA expression that was associated with a prominent increase in nuclear factor-erythroid 2-related factor 2 (Nrf2) protein. Induction of HO-1 was also observed in rat carotid arteries after the in vivo application of AICAR. Induction of HO-1 by AICAR was blocked by the AMPK inhibitor compound C, the adenosine kinase inhibitor 5′-iodotubercidin, and by silencing AMPK-α1/2 and was mimicked by the AMPK activator A-769662 and by infecting ECs with an adenovirus expressing constitutively active AMPK-α1. AICAR also induced a significant rise in HO-1 promoter activity that was abolished by mutating the antioxidant responsive elements of the HO-1 promoter or by the overexpression of dominant negative Nrf2. Finally, activation of AMPK inhibited cytokine-mediated EC death, and this was prevented by the HO inhibitor tin protoporphyrin-IX or by silencing HO-1 expression. In conclusion, AMPK stimulates HO-1 gene expression in human ECs via the Nrf2/antioxidant responsive element signaling pathway. The induction of HO-1 mediates the antiapoptotic effect of AMPK, and this may provide an important adaptive response to preserve EC viability during periods of metabolic stress. PMID:21037234

Non-coding RNA derived from the region adjacent to the human HO-1 E2 enhancer selectively regulates HO-1 gene induction by modulating Pol II binding

PubMed Central

Maruyama, Atsushi; Mimura, Junsei; Itoh, Ken

2014-01-01

Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation. However, it remains unclear whether eRNAs are involved in the regulation of human heme oxygenase-1 gene (HO-1) induction. Here, we report that multiple nuclear-enriched eRNAs are transcribed from the regions adjacent to two human HO-1 enhancers (i.e. the distal E2 and proximal E1 enhancers), and some of these eRNAs are induced by the oxidative stress-causing reagent diethyl maleate (DEM). We demonstrated that the expression of one forward direction (5′ to 3′) eRNA transcribed from the human HO-1 E2 enhancer region (named human HO-1enhancer RNA E2-3; hereafter called eRNA E2-3) was induced by DEM in an NRF2-dependent manner in HeLa cells. Conversely, knockdown of BACH1, a repressor of HO-1 transcription, further increased DEM-inducible eRNA E2-3 transcription as well as HO-1 expression. In addition, we showed that knockdown of eRNA E2-3 selectively down-regulated DEM-induced HO-1 expression. Furthermore, eRNA E2-3 knockdown attenuated DEM-induced Pol II binding to the promoter and E2 enhancer regions of HO-1 without affecting NRF2 recruitment to the E2 enhancer. These findings indicate that eRNAE2-3 is functional and is required for HO-1 induction. PMID:25404134

HOED: Hypermedia Online Educational Database.

ERIC Educational Resources Information Center

Duval, E.; Olivie, H.

This paper presents HOED, a distributed hypermedia client-server system for educational resources. The aim of HOED is to provide a library facility for hyperdocuments that is accessible via the world wide web. Its main application domain is education. The HOED database not only holds the educational resources themselves, but also data describing…

Patent urachus repair

MedlinePlus

... children. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... surgery. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Inflatable artificial sphincter

MedlinePlus

... children. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... women. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Bladder outlet obstruction

MedlinePlus

... failure. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... failure. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

Obituary: Peter Robert Wilson, 1929-2007

NASA Astrophysics Data System (ADS)

Snodgrass, Herschel B.

2009-01-01

It is with great sadness that I report the passing of Peter Robert Wilson, a well-known and well-loved figure in the solar physics community. Peter was on the faculty of the Department of Applied Mathematics at the University of Sydney for 39 years, and Chair of the department for 24 of these years. He was the author or co-author of more than 80 scientific research papers and a book, Solar and Stellar Activity Cycles (1994), published by Cambridge University Press. He died suddenly of a heart attack, at his home in Glebe, Australia, in the early morning of 11 November 2007. Peter was an organizer of, and participant in, many international conferences and workshops. He traveled extensively, holding visiting appointments at the University of Colorado (JILA), at Cambridge University, at the College de France (Paris), and at the California Institute of Technology [CalTech]. Most of his work was in the field of solar physics, but he also did some work on the philosophy of science and on tides. Peter came from a line of mathematicians. His father, Robert Wilson, immigrated to Australia from Glasgow in 1911, and became a mathematics teacher at Scotch College, a private school in Melbourne. There his name was changed to 'Bill' because 'Bob' was already taken." Peter's enjoyment of this story as characteristic of Australian academia (as any fan of Monty Python would understand) is indicative of his infectious sense of humor. In a similar vein, he claimed ancestry traced back to the eighteenth-century Scottish mathematician Alexander Wilson, Professor of Astronomy at the University of Glasgow. That Wilson is famous in the solar physics community for his discovery, known as the "Wilson Effect," of the photospheric depressions associated with sunspots. Peter himself could not resist writing a paper on this subject, and was delighted when the bait was taken by some less-informed colleagues who chided him for "naming an effect after himself." "Bill" Wilson married Naomi Christian, a Melbourne native, and together they had three children. Peter was the eldest; he was born on 17 October 1929. He attended Scotch College, where his father taught, and went on to the University of Melbourne where he eventually earned an M. Sc. in experimental physics. This was not his cup of tea, however, and he first endeavored to follow in his father's footsteps, taking short-term appointments teaching mathematics at the secondary-school level abroad, in England, and in Scotland. After a few years Peter returned to Melbourne and took a post at Scotch College following his father's retirement. He soon decided, however, that teaching young boys in a private school was not his cup of tea either, and in 1959 he secured a position in applied mathematics at the University of Sydney. He had just married his first wife, Margaret, and they moved north together to start their family. Peter flourished at the University of Sydney, but his advancement in rank was hampered by the lack of a Ph. D. The problem was solved by Ron Giovanelli, Chief of the Division of Physics at Australia's Commonwealth Scientific and Industrial Research Organization [CSIRO], an astrophysicist whose interest lay in the transfer of radiation through the outer layers in the Sun. Giovanelli took Peter on as a thesis student. This both earned him the needed Ph. D. and started him on his research career in solar physics. He now began to move up the academic ladder at Sydney. To satisfy his love of adventure, Peter was also able to take a series of visiting positions in the United States, working with Dick Thomas and others at JILA and Sacramento Peak Observatory (National Solar Observatory) in New Mexico. During this time he created a framework for further collaborations that became known as the Sydney-Boulder Astrophysics Association [SBAA]. In 1971 Peter was appointed Professor and Chair of the Department of Applied Mathematics at Sydney, and for the next two decades he worked hard to strengthen this department. He was very successful in this endeavor; he had a reputation for fairness and honesty and was well liked. Under his leadership the department grew in both size and quality. Peter fostered a group of outstanding students, including Chris Cannon, David Rees, and Lawrence Cram. One of his proudest accomplishments was to recruit several women onto the faculty and to increase the number of female students. One of these, Nalini Joshi, is presently Head of School. After Peter resigned as Chair, he went on to several other positions associated with the governance of the University, including the Academic Senate, the Governing Council of the Women's College, and the Board of Trustees. Peter and his first wife were divorced in 1982, after their two children, Sally and Michael, had grown up and left home. A few years later he met and married Geraldine Barnes, a Senior Lecturer in the English Department. This proved to be a fabulous match; they supported each other's academic pursuits, attended each other's conferences, enjoyed a rich social life centered around the university, and traveled extensively together. Their marriage helped both of them refocus their careers. Geraldine steadily advanced in rank, and is now Head of the School of Letters, Arts and the Media. Peter became one of the chief organizers of a series of workshops focused on the solar activity cycle. The first solar cycle workshop was held in 1986 at CalTech's Big Bear Solar Observatory [BBSO], and it was at this meeting that I first met Peter. There were three subsequent meetings, roughly a year apart, held at the University of Sydney, at Stanford's Fallen Leaf Lake in the Sierras, and at Sacramento Peak Observatory, and these were very successful in bringing together the main players in this research field. My subsequent association with Peter involved several trips back and forth between Portland (Oregon), Boulder, and Sydney and collaborations on about a dozen controversial research papers. Together with Peter Fox and Pat McIntosh, we became the solar-physics "gang of four." A dinner in Sydney with Geraldine, Peter, and their friends always meant liberal amounts of fine Australian wine, lively conversations on every imaginable topic (except physics), much laughter, and a deliciously endless meal. A weekend at their beach house in Killcare was even better, featuring long walks on the golden-sand beach and in the nearby bush. Kookaburras, Currawongs, and Rainbow Lorikeets frequented the outdoor deck, and the bush teemed with large and fascinating spiders. Back in Sydney, short-term visitors enjoyed lodgings and excellent breakfasts at the University of Sydney's Women's College, with Peter on the Council. Peter was a man of many interests. He was an expert sailor, a small-plane pilot who took colleagues and friends on adventurous flights, and a lover of sports. He was a skier, a hiker, and a good tennis player who disdained proper form but usually won the point. In 1994, one day after his 65th birthday, Peter suffered a serious stroke. Recovery from this was extremely difficult, painful, and slow; he did, however, recover to a remarkable degree. He had to learn to walk all over again and his vocal chords were partially paralyzed, but after several years of determined work, Peter was able to play a little tennis and squash, and he could bowl and hike. During the last decade of his life he traveled to Easter Island, to the Galapagos, and to the Ross Ice Shelf in Antarctica. Peter continued to take pleasure in his research to the end, in collaboration with close colleagues who were always among his closest friends. Among these was Chris Durrant, who had been Head of the School of Mathematics and Statistics from 1994 to 1998. They were writing a series of papers on the mechanism of the Sun's polar field reversals. I was looking forward to joining them this coming summer. My last visit with Peter was in Phoenix, Arizona, where Geraldine was participating in a conference. We hiked into the Superstition Mountains, and I remember him walking slowly, being careful of his balance, but going the whole distance with pride and in good spirits. Peter was a truly remarkable man with, as Geraldine has put it, "a genuine gift for leadership and the encouragement of team spirit." He was a creative and productive scientist with a tremendous life force, a great sense of adventure, and a warm heart. My own collaborations with him were a joy. His death is a sad loss to all who knew him, and he will be sorely missed, but Peter R. Wilson lived life to the fullest and gave his best to the world. We should be glad for him. At the end of his (unpublished) autobiography, where he describes his recovery from the stroke, he writes: "So as I forecast in 1994, I have continued to 'soldier on', and must admit that a miracle has indeed occurred, at least 80%; I wouldn't have missed the past ten years for anything. Who knows what the inevitable advance of old age may hold, but I cannot complain that I have been 'short changed' in any way."

ARC-2007-ACD07-0152-030

NASA Image and Video Library

2007-08-12

Perseid Meteor flight on Google's Gulfstream Aircraft. P.I. Peter Jenniskens, SETI Group Peter Jenniskens, SETI - briefing w/L-R; J Nott, P Jenniskens, M Koop, D Holman and two Apex Aviation Corp reps.

1. DOWNRIVER VIEW OF BRIDGE, LOOKING SOUTHSOUTHWEST Peter J. Edwards, ...

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

1. DOWNRIVER VIEW OF BRIDGE, LOOKING SOUTH-SOUTHWEST Peter J. Edwards, photographer, August 1988 - Four Mile Bridge, Copper Creek Road, Spans Table Rock Fork, Mollala River, Molalla, Clackamas County, OR

Chymotrypsin Test

MedlinePlus

... Peter Jacky, PhD, FACMG. Director of Cytogenetics and Molecular Genetics, Airport Way Regional Laboratory, Portland, OR. Wu, A. ( ... Denise I. Quigley, PhD, FACMG. Co-Director Cytogenetics/Molecular Genetics, Airport Way Regional Laboratory, Portland, OR. Peter Jacky, ...

Trypsinogen Test

MedlinePlus

... Peter Jacky, PhD, FACMG. Director of Cytogenetics and Molecular Genetics, Airport Way Regional Laboratory, Portland, OR. (Update October ... Denise I. Quigley, PhD, FACMG. Co-Director Cytogenetics/Molecular Genetics, Airport Way Regional Laboratory, Portland, OR. Peter Jacky, ...

78 FR 3034 - Sunshine Act Meeting; Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-15

... by email at [email protected] . FOR MEDIA INFORMATION CONTACT: Peter Knudson (202) 314-6219 or by email at peter[email protected] . Dated: January 11, 2013. Candi R. Bing, Federal Register Liaison Officer...

Tutorials for Africa - Diarrhea: MedlinePlus

MedlinePlus

... Judith Allsaints Apio Chaudhari Mugdha Ramachandra Richard Lunyata Peter Agaba Elizabeth Nakabuye Team of medical students in ... Valentine Kahababo Art and audio team - Kampala, Uganda Peter Mukiibi Kenneth Nek Daniel Hama Contact the Makerere ...

Prostate resection - minimally invasive - discharge

MedlinePlus

... approaches. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... hyperplasia. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

78 FR 64541 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... by email at [email protected] . FOR MEDIA INFORMATION CONTACT: Peter Knudson, (202) 314-6100 or by email at peter[email protected] . Dated: Friday, October 25, 2013. Candi R. Bing, Federal Register Liaison...

Genetics Home Reference: Rubinstein-Taybi syndrome

MedlinePlus

... Breuning MH, Niedrist D, Hennekam RC, Schinzel A, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation ... JT, van Ommen GJ, Breuning MH, Hennekam RC, Peters DJ. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations ...

Professor Peter Choyce: an early pioneer of intraocular lenses and corneal/refractive surgery.

PubMed

Pandey, Suresh K; Apple, David J

2005-06-01

Professor Peter Choyce, FRCS, DOMS, MS, was one of the pioneers of intraocular lens implant surgery. He developed an interest in artificial lens implantation following cataract surgery, a procedure that was widely criticized by the ophthalmic establishment in the UK, Europe, North America and other countries. Owing to the opposition to the intraocular lenses, Peter Choyce together with Sir Harold Ridley co-founded the International Intraocular Implant Club in 1966, which was responsible for the gradual acceptance of artificial lens implantation. Peter Choyce developed several models of intraocular lens, but did not patent the majority of them. The Choyce Mark IX, manufactured by Rayner Intraocular Lenses, became the first US Food and Drug Administration-approved intraocular lens in 1981. A review of Peter Choyce's record confirms a significant number of original innovations in the field of anterior segment surgery, including many procedures taken for granted today, but not associated with his name. These include early work on both kerato- and intraocular lens-refractive procedures, keratoprosthesis, pioneering paediatric implant procedures and others. Unfortunately his tenacious adherence to anterior chamber lens technology, while in general clinically sound, caused many to question his influence and hence he remained poorly understood even until after his death. He passed away on 8 August 2001 after a long fight with colon cancer. In this article, we provide evidence and elaborate Peter Choyce's accomplishments, which places him as one of the most innovative ophthalmologist in his surgical field in the twentieth century.

Selective activation of heme oxygenase-2 by menadione.

PubMed

Vukomanovic, Dragic; McLaughlin, Brian E; Rahman, Mona N; Szarek, Walter A; Brien, James F; Jia, Zongchao; Nakatsu, Kanji

2011-11-01

While substantial progress has been made in elucidating the roles of heme oxygenases-1 (HO-1) and -2 (HO-2) in mammals, our understanding of the functions of these enzymes in health and disease is still incomplete. A significant amount of our knowledge has been garnered through the use of nonselective inhibitors of HOs, and our laboratory has recently described more selective inhibitors for HO-1. In addition, our appreciation of HO-1 has benefitted from the availability of tools for increasing its activity through enzyme induction. By comparison, there is a paucity of information about HO-2 activation, with only a few reports appearing in the literature. This communication describes our observations of the up to 30-fold increase in the in-vitro activation of HO-2 by menadione. This activation was due to an increase in Vmax and was selective, in that menadione did not increase HO-1 activity.

Nano-jewels in biology. Gold and platinum on diamond nanoparticles as antioxidant systems against cellular oxidative stress.

PubMed

Martín, Roberto; Menchón, Cristina; Apostolova, Nadezda; Victor, Victor M; Alvaro, Mercedes; Herance, José Raúl; García, Hermenegildo

2010-11-23

Diamond nanoparticles (DNPs) obtained by explosive detonation have become commercially available. These commercial DNPs can be treated under Fenton conditions (FeSO(4) and H(2)O(2) at acidic pH) to obtain purer DNP samples with a small average particle size (4 nm) and a large population of surface OH groups (HO-DNPs). These Fenton-treated HO-DNPs have been used as a support of gold and platinum nanoparticles (≤2 nm average size). The resulting materials (Au/HO-DNP and Pt/HO-DNP) exhibit a high antioxidant activity against reactive oxygen species induced in a hepatoma cell line. In addition to presenting good biocompatibility, Au/HO- and Pt/HO-DNP exhibit about a two-fold higher antioxidant activity than glutathione, one of the reference antioxidant systems. The most active material against cellular oxidative stress was Au/HO-DNP.

Topics in Ho Morphophonology and Morphosyntax

ERIC Educational Resources Information Center

Pucilowski, Anna

2013-01-01

Ho, an under-documented North Munda language of India, is known for its complex verb forms. This dissertation focuses on analysis of several features of those complex verbs, using data from original fieldwork undertaken by the author. By way of background, an analysis of the phonetics, phonology and morphophonology of Ho is first presented. Ho has…

Is the Health of the Nation Outcome Scales appropriate for the assessment of symptom severity in patients with substance-related disorders?

PubMed

Andreas, Sylke; Harries-Hedder, Karin; Schwenk, Wolfgang; Hausberg, Maria; Koch, Uwe; Schulz, Holger

2010-07-01

The Health of the Nation Outcome Scales (HoNOS) is an internationally established clinician-rated instrument. The aim of the study was to assess the psychometric properties in inpatients with substance-related disorders. The HoNOS was applied in a multicenter, consecutive sample of 417 inpatients. Interrater reliability coefficients, confirmatory factor analysis, and regression tree analyses were calculated to assess the reliability and validity of the HoNOS. The factor validity of the HoNOS and its total score could not be confirmed. After training, all items of the HoNOS revealed sufficient values of interrater reliabilities. As the results of the regression tree analyses showed, the single items of the HoNOS were one of the most important predictor of service utilization. The HoNOS can be recommended for obtaining detailed ratings of the problems of inpatients with substance-related disorders as a clinical application in routine mental health care at present. Further studies should include comparisons of HoNOS and Addiction Severity Index. Copyright 2010 Elsevier Inc. All rights reserved.

Parameter selection with the Hotelling observer in linear iterative image reconstruction for breast tomosynthesis

NASA Astrophysics Data System (ADS)

Rose, Sean D.; Roth, Jacob; Zimmerman, Cole; Reiser, Ingrid; Sidky, Emil Y.; Pan, Xiaochuan

2018-03-01

In this work we investigate an efficient implementation of a region-of-interest (ROI) based Hotelling observer (HO) in the context of parameter optimization for detection of a rod signal at two orientations in linear iterative image reconstruction for DBT. Our preliminary results suggest that ROI-HO performance trends may be efficiently estimated by modeling only the 2D plane perpendicular to the detector and containing the X-ray source trajectory. In addition, the ROI-HO is seen to exhibit orientation dependent trends in detectability as a function of the regularization strength employed in reconstruction. To further investigate the ROI-HO performance in larger 3D system models, we present and validate an iterative methodology for calculating the ROI-HO. Lastly, we present a real data study investigating the correspondence between ROI-HO performance trends and signal conspicuity. Conspicuity of signals in real data reconstructions is seen to track well with trends in ROI-HO detectability. In particular, we observe orientation dependent conspicuity matching the orientation dependent detectability of the ROI-HO.

Phase relations in the system Cu-Ho-O and stability of Cu{sub 2}Ho{sub 2}O{sub 5}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, T.; Jacob, K.T.

1994-01-01

The phase relations in the system Cu-Ho-O have been determined at 1300 K using X-ray diffraction, optical microscopy, and electron microprobe analysis of samples equilibrated in evacuated quartz ampules and in pure oxygen. Only one ternary compound, Cu{sub 2}Ho{sub 2}O{sub 5}, was found to be stable. The Gibbs free energy of formation of this compound has been measured. Since the formation is endothermic, Cu{sub 2}Ho{sub 2}O{sub 5} becomes thermodynamically unstable with respect to CuO and Ho{sub 2}O{sub 3} below 810 K. When the oxygen partial pressure over Cu{sub 2}Ho{sub 2}O{sub 5} is lowered, it decomposes. The decomposition temperature at anmore » oxygen partial pressure of 1.52 X 10{sup 4} Pa was measured using a combined DTA-TGA apparatus. Based on these results, an oxygen potential diagram for the system Cu-Ho-O at 1300 K is presented.« less

Heme oxygenase-1 in tumor biology and therapy.

PubMed

Was, Halina; Dulak, Jozef; Jozkowicz, Alicja

2010-12-01

Heme oxygenase-1 (HO-1) degrades heme to carbon monoxide (CO), biliverdin, and ferrous iron. As HO-1 expression is highly increased by stressful conditions, the major role of the enzyme is the protection against oxidative injury. Additionally, it regulates cell proliferation, modulates inflammatory response and facilitates angiogenesis. Beneficial activities of HO-1 have been recognized in many pathological states e.g. atherosclerosis, diabetes, ischemia/reperfusion injury or organ transplantation. Interestingly HO-1 expression is very often boosted in tumor tissues and could be further elevated in response to radio-, chemo-, or photodynamic therapy. A growing body of evidence suggests that HO-1 may play a role in tumor induction and can potently improve the growth and spread of tumors. This review discusses the implications of HO-1 properties for tumor proliferation and cell death, differentiation, angiogenesis and metastasis, and tumor-related inflammation. Finally, it suggests that pharmacological agents that regulate HO activity or HO-1 gene silencing may become powerful tools for preventing the onset or progression of various cancers and sensitize them to anticancer therapies.

Synthesis, crystal structure, optical and thermal properties of lanthanide hydrogen-polyphosphates Ln[H(PO3)4] (Ln = Tb, Dy, Ho).

PubMed

Förg, Katharina; Höppe, Henning A

2015-11-28

Lanthanide hydrogen-polyphosphates Ln[H(PO3)4] (Ln = Tb, Dy, Ho) were synthesised as colourless (Ln = Tb, Dy) and light pink (Ln = Ho) crystalline powders by reaction of Tb4O7/Dy2O3/Ho2O3 with H3PO3 at 380 °C. All compounds crystallise isotypically (P2(1)/c (no. 14), Z = 4, a(Tb) = 1368.24(4) pm, b(Tb) = 710.42(2) pm, c(Tb) = 965.79(3) pm, β(Tb) = 101.200(1)°, 3112 data, 160 parameters, wR2 = 0.062, a(Ho) = 1363.34(5) pm, b(Ho) = 709.24(3) pm, c(Ho) = 959.07(4) pm, β(Ho) = 101.055(1)°, 1607 data, 158 parameters, wR2 = 0.058). The crystal structure comprises two different infinite helical chains of corner-sharing phosphate tetrahedra. In-between these chains the lanthanide ions are located, coordinated by seven oxygen atoms belonging to four different polyphosphate chains. Vibrational, UV/Vis and fluorescence spectra of Ln[H(PO3)4] (Ln = Tb, Dy, Ho) as well as Dy[H(PO3)4]:Ln (Ln = Ce, Eu) and the magnetic and thermal behaviour of Tb[H(PO3)4] are reported.

Overexpressed human heme Oxygenase-1 decreases adipogenesis in pigs and porcine adipose-derived stem cells.

PubMed

Park, Eun Jung; Koo, Ok Jae; Lee, Byeong Chun

2015-11-27

Adipose-derived mesenchymal stem cells (ADSC) are multipotent, which means they are able to differentiate into several lineages in vivo and in vitro under proper conditions. This indicates it is possible to determine the direction of differentiation of ADSC by controlling the microenvironment. Heme oxygenase 1 (HO-1), a type of antioxidant enzyme, attenuates adipogenicity and obesity. We produced transgenic pigs overexpressing human HO-1 (hHO-1-Tg), and found that these animals have little fatty tissue when autopsied. To determine whether overexpressed human HO-1 suppresses adipogenesis in pigs, we analyzed body weight increases of hHO-1-Tg pigs and wild type (WT) pigs of the same strain, and induced adipogenic differentiation of ADSC derived from WT and hHO-1-Tg pigs. The hHO-1-Tg pigs had lower body weights than WT pigs from 16 weeks of age until they died. In addition, hHO-1-Tg ADSC showed reduced adipogenic differentiation and expression of adipogenic molecular markers such as PPARγ and C/EBPα compared to WT ADSC. These results suggest that HO-1 overexpression reduces adipogenesis both in vivo and in vitro, which could support identification of therapeutic targets of obesity and related metabolic diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds

PubMed Central

Rahman, Mona N.; Vukomanovic, Dragic; Vlahakis, Jason Z.; Szarek, Walter A.; Nakatsu, Kanji; Jia, Zongchao

2013-01-01

The development of heme oxygenase (HO) inhibitors, especially those that are isozyme-selective, promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties and may play a role in several disease states, making it an enticing therapeutic target. Traditionally, the metalloporphyrins have been used as competitive HO inhibitors owing to their structural similarity with the substrate, heme. However, given heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), non-selectivity is an unfortunate side-effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort to develop novel compounds as potent, selective inhibitors of HO. This resulted in the creation of non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated, which provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. PMID:23097500

Expression of Heme Oxygenase-1 in Thick Ascending Loop of Henle Attenuates Angiotensin II-Dependent Hypertension

PubMed Central

Drummond, Heather A.; Gousette, Monette U.; Storm, Megan V.; Abraham, Nader G.; Csongradi, Eva

2012-01-01

Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang II delivered by an osmotic minipump for 10 days (139±3 versus 153±2 mmHg in the transgenic and control mice, respectively; P<0.05). The lower blood pressure in transgenic mice associated with a 60% decrease in medullary NKCC2 transporter expression determined by Western blot. Transgenic mice also exhibited a 36% decrease in ouabain-sensitive sodium reabsorption and a significantly attenuated response to furosemide in isolated TALH segments,. In summary, these results show that increased levels of HO-1 in the TALH can lower blood pressure by a mechanism that may include alterations in NKCC2-dependent sodium reabsorption. PMID:22323644

Controlled synthesis, formation mechanism, and carbon oxidation properties of Ho2Cu2O5 nanoplates prepared with a coordination-complex method

NASA Astrophysics Data System (ADS)

Guo, Rui; You, Junhua; Han, Fei; Li, Chaoyang; Zheng, Guiyuan; Xiao, Weicheng; Liu, Xuanwen

2017-02-01

Ho2Cu2O5 nanoplates with perovskite structures were synthesized via a simple solution method (SSM) and a coordination-complex method (CCM) using [HoCu(3,4-pdc)2(OAc)(H2O)3]·8H2O (L = 3,4-pyridinedicarboxylic acid) as a precursor. The CCM was also performed in an N2 environment (CCMN) under various calcination conditions. The crystallization processes were characterized using X-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. Ho2Cu2O5 formed through the diffusion of CuO into Ho2O3 particles. Cu2+ diffused faster than Ho3+ during this process. The initial products of CCMN (along with the thermal decomposition products) were initially laminarized in the N2 atmosphere, which prevented the growth of CuO particles and decreased the size of the Ho2Cu2O5 particles. The final Ho2Cu2O5 particles from CCMN had a nanoplate morphology with an average thickness of 75 nm. The decomposition of organic molecules and protection from N2 played important roles in determining the morphology of the resulting Ho2Cu2O5. The catalytic oxidation activity of Ho2Cu2O5 samples for carbon was characterized using a specific surface area measurement and thermogravimetric analysis, which revealed that the samples produced by CCMN had the highest catalytic activity.

Optical spectroscopy and luminescence properties of Ho3+ doped zinc fluorophosphate (ZFP) glasses for green luminescent device applications

NASA Astrophysics Data System (ADS)

Reddy Prasad, V.; Damodaraiah, S.; Ratnakaram, Y. C.

2018-04-01

Ho3+ doped zinc fluorophosphate (ZFP) glasses with molar chemical compositions, (60-x) NH4H2PO4+20ZnO+10BaF2+10NaF+xHo2O3 (where x = 0.1, 0.3, 0.5, 1.0 and 1.5 mol%) were prepared by melt quenching technique. These glasses were characterized through physical, structural, optical, excitation, luminescence and decay curve analysis. From the absorption spectra, spectral intensities (fexp and fcal), Judd-Ofelt intensity parameters (Ω2, Ω4 and Ω6), radiative transition probabilities (AT), radiative lifetimes (τR) and branching ratios (βR) were evaluated for all Ho3+ doped ZFP glass matrices. From the photoluminescence spectra, peak stimulated emission cross-sections (σP) were calculated for all Ho3+ doped ZFP glasses. The Ho3+ doped ZFP glasses show strong green emission at 545 nm and red emission at 656 nm under excitation, 450 nm. The measured lifetimes (τmeas) of (5S2)5F4 level of Ho3+ doped ZFP glasses were obtained from decay profiles. The CIE color coordinates of Ho3+ doped ZFP glasses were calculated from emission spectra and 1.0 mol% of Ho3+ doped ZFP glass matrix gives green emission. Hence, these results confirm that the Ho3+ doped ZFP glasses could be considered as a promising candidate for visible green laser applications.

Perceptions About the Present and Future of Surgical Simulation: A National Study of Mixed Qualitative and Quantitative Methodology.

PubMed

Yiasemidou, Marina; Glassman, Daniel; Tomlinson, James; Song, David; Gough, Michael J

Assess expert opinion on the current and future role of simulation in surgical education. Expert opinion was sought through an externally validated questionnaire that was disseminated electronically. Heads of Schools of Surgery (HoS) (and deputies) and Training Program Directors (TPD) (and deputies). Simulation was considered a good training tool (HoS: 15/15, TPD: 21/21). The concept that simulation is useful mostly to novices and for basic skills acquisition was rejected (HoS: 15/15, TPDs: 21/21; HoS: 13/15, TPDs: 18/21). Further, simulation is considered suitable for teaching nontechnical skills (HoS: 13/15, TPDs: 20/21) and re-enacting stressful situations (HoS: 14/15, TPDs: 15/21). Most respondents also felt that education centers should be formally accredited (HoS: 12/15, TPDs: 16/21) and that consultant mentors should be appointed by every trust (HoS: 12/15, TPDs: 19/21). In contrast, there were mixed views on its use for trainee assessment (HoS: 6/15, TPDs: 14/21) and whether it should be compulsory (HoS: 8/15, TPDs: 11/21). The use of simulation for the acquirement of both technical and nontechnical skills is strongly supported while views on other applications (e.g., assessment) are conflicting. Further, the need for center accreditation and supervised, consultant-led teaching is highlighted. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

The role of heme oxygenase-1 in systemic-onset juvenile idiopathic arthritis.

PubMed

Takahashi, Akitaka; Mori, Masaaki; Naruto, Takuya; Nakajima, Shoko; Miyamae, Takako; Imagawa, Tomoyuki; Yokota, Shumpei

2009-01-01

We have determined the serum levels of heme oxygenase-1 (HO-1) in 56 patients with systemic-onset juvenile idiopathic arthritis (s-JIA) and compared these with serum HO-1 levels in healthy controls and patients with other pediatric rheumatic diseases. Serum HO-1 levels were measured by the sandwich enzyme-linked immunosorbent assay. The mean serum HO-1 level in s-JIA patients during the active phase was 123.6 +/- 13.83 ng/ml, which was significantly higher than that in patients with polyarticular juvenile idiopathic arthritis (p-JIA), Kawasaki disease, systemic lupus erythematosus or mixed connective tissue disease (P < 0.0005). The serum levels of HO-1, cytokines and cytokine receptors in patients with s-JIA were also assessed at both the active and inactive phases. The serum HO-1 level in patients with s-JIA in the active phase was found to be significantly greater than that in patients with the disease in the inactive phase (P < 0.0001). An assessment of the relationships between serum HO-1 levels and other laboratory parameters or cytokines in patients with s-JIA did not reveal any strong correlations. These results suggest that the serum level of HO-1 may be a useful marker for the differential diagnosis of s-JIA. Further study will be necessary to elucidate the mechanism of HO-1 production and to clarify the role of HO-1 in the disease process.

Down-regulation of cellular protein heme oxygenase-1 inhibits proliferation of avian influenza virus H9N2 in chicken oviduct epithelial cells.

PubMed

Qi, Xuefeng; Zhang, Huizhu; Xue, Tianxia; Yang, Bo; Deng, Meiyu; Wang, Jingyu

2018-01-01

The pathogenesis of H9N2 subtype avian influenza virus (AIV) infection in hens is often related to oviduct tissue damage. Our previous study suggested that H9N2 AIV induces cellular apoptosis by activating reactive oxygen species (ROS) accumulation and mitochondria-mediated apoptotic signalling in chicken oviduct epithelial cells (COECs). Heme oxygenase-1 (HO-1) is an inducible enzyme that exerts protective effects against oxidative stress and activated HO-1 was recently shown to have antiviral activity. To study the potential involvement of HO-1 in H9N2 AIV proliferation, the role of its expression in H9N2-infected COECs was further investigated. Our results revealed that H9N2 AIV infection significantly up-regulated the expression of HO-1 and that HO-1 down-regulation by ZnPP, a classical inhibitor of HO-1, could inhibit H9N2 AIV replication in COECs. Similarly, the small interfering RNA (siRNA)-mediated knockdown of HO-1 also markedly decreased the virus production in H9N2-infected COECs. In contrast, adenoviral-mediated over-expression of HO-1 concomitantly promoted H9N2 AIV replication. Taken together, our study demonstrated the involvement of HO-1 in AIV H9N2 proliferation, and these findings suggested that HO-1 is a potential target for inhibition of AIV H9N2 replication.

Upregulation of heme oxygenase-1 protected against brain damage induced by transient cerebral ischemia-reperfusion injury in rats.

PubMed

Lu, Xiufang; Gu, Renjun; Hu, Weimin; Sun, Zhitang; Wang, Gaiqing; Wang, Li; Xu, Yuming

2018-06-01

The aim of the present study was to identify the effect of heme oxygenase (HO)-1 gene on cerebral ischemia-reperfusion injury. Sprague-Dawley rats were divided randomly into four groups: Sham group, vehicle group, empty adenovirus vector (Ad) group and recombinant HO-1 adenovirus (Ad-HO-1) transfection group. Rats in the vehicle, Ad and Ad-HO-1 groups were respectively injected with saline, Ad or Ad-HO-1 for 3 days prior to cerebral ischemia-reperfusion injury. Subsequently, the middle cerebral artery occlusion method was used to establish the model of cerebral ischemia-reperfusion injury. Following the assessment of neurological function, rats were sacrificed, and the infarction volume and apoptotic index in rat brains were measured. Furthermore, the protein expression levels of HO-1 in brain tissues were detected using western blot analysis. Results indicated that the neurological score of the Ad-HO-1 group was significantly increased compared with the Ad or vehicle groups, respectively (P<0.001). The volume of cerebral infarction and the index score of neuronal apoptosis in the vehicle and Ad groups was significantly increased compared with the Ad-HO-1 group (P<0.01). The death of neuronal cells following cerebral ischemia-reperfusion injury reduced remarkably induced by over-expression of HO-1. These findings suggest a neuroprotective role of HO-1 against brain injury induced by transient cerebral ischemia-reperfusion injury.

Inhibition of the NADPH oxidase regulates HO-1 expression in chronic myeloid leukemia

PubMed Central

Singh, Melissa M.; Irwin, Mary E.; Gao, Yin; Ban, Kechen; Shi, Ping; Arlinghaus, Ralph B.; Amin, Hesham M.; Chandra, Joya

2011-01-01

Background Patients with blast crisis phase chronic myelogeneous leukemia (CML) have poor response to tyrosine kinase inhibitors designed to inhibit the BCR-ABL1 oncogene. Recent work has shown that heme oxygenase 1 (HO-1) expression is increased in BCR-ABL1 expressing cells and that inhibition of HO-1 in CML leads to reduced cellular growth suggesting HO-1 may be a plausible target for therapy. Here we sought to clarify the mechanism of HO-1 overexpression and the role of the NADPH oxidase as a contributor to this mechanism in CML. Methods HO-1 expression was evaluated in CML bone marrow specimens from patients in various stages of disease, in a transplant based model for CML and in CML cell lines. Chemical and genetic inhibition of the NADPH oxidase was carried out in CML cells. Results Blast crisis CML patient specimens displayed higher levels of HO-1 staining than chronic or accelerated phase. HO-1 upregulation in BCR-ABL1 expressing cells was suppressed by diphenyliodonium (DPI), a chemical inhibitor of the NADPH oxidase. Targeting the NADPH oxidase through RNAi to Rac1, a dominant negative Rac1 construct or an inhibitor of Rac1 activity also blunted HO-1 protein expression. Moreover, inhibition of the NADPH oxidase by RNAi directed towards p47phox similarly abrogated HO-1 levels. Conclusion BCR-ABL1 expression upregulates HO-1, a survival factor for CML cells. This upregulation is more pronounced in blast crisis CML relative to early stage disease and is mediated by the NADPH oxidase components Rac1 and p47phox. Expression of p47phox is increased in BCR-ABL1 expressing cells. PMID:22139798

Ulinastatin activates haem oxygenase 1 antioxidant pathway and attenuates allergic inflammation

PubMed Central

Song, Dongmei; Song, Geng; Niu, Yinghao; Song, Wei; Wang, Jiantao; Yu, Lei; Yang, Jianwang; Lv, Xin; Steinberg, Harry; Liu, Shu Fang; Wang, Baoshan

2014-01-01

Background and Purpose Ulinastatin (UTI), a serine protease inhibitor, was recently found to have an anti-inflammatory action. However, the mechanisms mediating this anti-inflammatory effect are not well understood. This study tested the hypothesis that UTI suppresses allergic inflammation by inducing the expression of haem oxygenase 1 (HO1). Experimental Approach Control mice and mice sensitized (on days 1, 9 and 14) and challenged (on days 21 to 27) with ovalbumin (OVA) were treated with UTI. The effects of UTI on basal expression of HO1 and that induced by OVA challenge were examined. The involvement of UTI-induced HO1 expression in anti-inflammatory and antioxidant effects of UTI was also evaluated. Key Results UTI markedly increased basal HO1 protein expression in lungs of control mice in a time- and dose-dependent manner, and augmented HO1 protein expression induced by OVA. The up-regulation of HO1 mediated by UTI in sensitized and OVA-challenged mice was associated with reduced airway inflammation, alleviated tissue injury, reduced oxidant stress and enhanced antioxidant enzyme activities. Inhibition of HO1 activity using HO1 inhibitor, zinc protoporphyrin, attenuated inhibitory effects of UTI on inflammation and oxidant stress, and its stimulant effects on antioxidant enzyme activities. Mechanistic analysis showed that UTI increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), stimulated Nrf2 DNA binding activity and concomitantly up-regulated HO1 mRNA expression. Conclusions and Implications UTI is a potent and naturally occurring inducer of HO1 expression. HO1 up-regulation contributes significantly to the anti-inflammatory and organ-protective effects of UTI, which has important research and therapeutic implications. PMID:24835359

Difference in occurrence of heterotopic ossification according to prosthesis type in the cervical artificial disc replacement.

PubMed

Yi, Seong; Kim, Keung Nyun; Yang, Moon Sul; Yang, Joong Won; Kim, Hoon; Ha, Yoon; Yoon, Do Heum; Shin, Hyun Chul

2010-07-15

Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 +/- 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 +/- 7.4 months) than the other groups. Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study.

Predicting the risk for hospital-onset Clostridium difficile infection (HO-CDI) at the time of inpatient admission: HO-CDI risk score.

PubMed

Tabak, Ying P; Johannes, Richard S; Sun, Xiaowu; Nunez, Carlos M; McDonald, L Clifford

2015-06-01

To predict the likelihood of hospital-onset Clostridium difficile infection (HO-CDI) based on patient clinical presentations at admission Retrospective data analysis Six US acute care hospitals Adult inpatients We used clinical data collected at the time of admission in electronic health record (EHR) systems to develop and validate a HO-CDI predictive model. The outcome measure was HO-CDI cases identified by a nonduplicate positive C. difficile toxin assay result with stool specimens collected >48 hours after inpatient admission. We fit a logistic regression model to predict the risk of HO-CDI. We validated the model using 1,000 bootstrap simulations. Among 78,080 adult admissions, 323 HO-CDI cases were identified (ie, a rate of 4.1 per 1,000 admissions). The logistic regression model yielded 14 independent predictors, including hospital community onset CDI pressure, patient age ≥65, previous healthcare exposures, CDI in previous admission, admission to the intensive care unit, albumin ≤3 g/dL, creatinine >2.0 mg/dL, bands >32%, platelets ≤150 or >420 109/L, and white blood cell count >11,000 mm3. The model had a c-statistic of 0.78 (95% confidence interval [CI], 0.76-0.81) with good calibration. Among 79% of patients with risk scores of 0-7, 19 HO-CDIs occurred per 10,000 admissions; for patients with risk scores >20, 623 HO-CDIs occurred per 10,000 admissions (P<.0001). Using clinical parameters available at the time of admission, this HO-CDI model demonstrated good predictive ability, and it may have utility as an early risk identification tool for HO-CDI preventive interventions and outcome comparisons.

Generation and Characterization of Human Heme Oxygenase-1 Transgenic Pigs

PubMed Central

Yang, Jaeseok; Cho, Bumrae; Hwang, Jong-Ik; Park, Sol Ji; Hurh, Sunghoon; Kim, Hwajung; Lee, Eun Mi; Ro, Han; Kang, Jung Taek; Kim, Su Jin; Won, Jae-Kyung; O'Connell, Philip J.; Kim, Hyunil; Surh, Charles D.; Lee, Byeong-Chun; Ahn, Curie

2012-01-01

Xenotransplantation using transgenic pigs as an organ source is a promising strategy to overcome shortage of human organ for transplantation. Various genetic modifications have been tried to ameliorate xenograft rejection. In the present study we assessed effect of transgenic expression of human heme oxygenase-1 (hHO-1), an inducible protein capable of cytoprotection by scavenging reactive oxygen species and preventing apoptosis caused by cellular stress during inflammatory processes, in neonatal porcine islet-like cluster cells (NPCCs). Transduction of NPCCs with adenovirus containing hHO-1 gene significantly reduced apoptosis compared with the GFP-expressing adenovirus control after treatment with either hydrogen peroxide or hTNF-α and cycloheximide. These protective effects were diminished by co-treatment of hHO-1 antagonist, Zinc protoporphyrin IX. We also generated transgenic pigs expressing hHO-1 and analyzed expression and function of the transgene. Human HO-1 was expressed in most tissues, including the heart, kidney, lung, pancreas, spleen and skin, however, expression levels and patterns of the hHO-1 gene are not consistent in each organ. We isolate fibroblast from transgenic pigs to analyze protective effect of the hHO-1. As expected, fibroblasts derived from the hHO-1 transgenic pigs were significantly resistant to both hydrogen peroxide damage and hTNF-α and cycloheximide-mediated apoptosis when compared with wild-type fibroblasts. Furthermore, induction of RANTES in response to hTNF-α or LPS was significantly decreased in fibroblasts obtained from the hHO-1 transgenic pigs. These findings suggest that transgenic expression of hHO-1 can protect xenografts when exposed to oxidative stresses, especially from ischemia/reperfusion injury, and/or acute rejection mediated by cytokines. Accordingly, hHO-1 could be an important candidate molecule in a multi-transgenic pig strategy for xenotransplantation. PMID:23071605

Risk factors for the development of heterotopic ossification in seriously burned adults: A National Institute on Disability, Independent Living and Rehabilitation Research burn model system database analysis.

PubMed

Levi, Benjamin; Jayakumar, Prakash; Giladi, Avi; Jupiter, Jesse B; Ring, David C; Kowalske, Karen; Gibran, Nicole S; Herndon, David; Schneider, Jeffrey C; Ryan, Colleen M

2015-11-01

Heterotopic ossification (HO) is a debilitating complication of burn injury; however, incidence and risk factors are poorly understood. In this study, we use a multicenter database of adults with burn injuries to identify and analyze clinical factors that predict HO formation. Data from six high-volume burn centers, in the Burn Injury Model System Database, were analyzed. Univariate logistic regression models were used for model selection. Cluster-adjusted multivariate logistic regression was then used to evaluate the relationship between clinical and demographic data and the development of HO. Of 2,979 patients in the database with information on HO that addressed risk factors for development of HO, 98 (3.5%) developed HO. Of these 98 patients, 97 had arm burns, and 96 had arm grafts. When controlling for age and sex in a multivariate model, patients with greater than 30% total body surface area burn had 11.5 times higher odds of developing HO (p < 0.001), and those with arm burns that required skin grafting had 96.4 times higher odds of developing HO (p = 0.04). For each additional time a patient went to the operating room, odds of HO increased by 30% (odds ratio, 1.32; p < 0.001), and each additional ventilator day increased odds by 3.5% (odds ratio, 1.035; p < 0.001). Joint contracture, inhalation injury, and bone exposure did not significantly increase odds of HO. Risk factors for HO development include greater than 30% total body surface area burn, arm burns, arm grafts, ventilator days, and number of trips to the operating room. Future studies can use these results to identify highest-risk patients to guide deployment of prophylactic and experimental treatments. Prognostic study, level III.

Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of bile duct in rats after liver transplantation.

PubMed

Zhan, Xi; Zhang, Zhiqing; Huang, Hanfei; Zhang, Yujun; Zeng, Zhong

2018-06-01

To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×10 8 /pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.

PubMed

Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

2004-04-01

Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, P<0.01). The reduction of interstitial fibrosis is accompanied by an increase in myocardial hHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.

Heme oxygenase-1 (HO-1) inhibits postmyocardial infarct remodeling and restores ventricular function.

PubMed

Liu, Xiaoli; Pachori, Alok S; Ward, Christopher A; Davis, J Paul; Gnecchi, Massimiliano; Kong, Deling; Zhang, Lunan; Murduck, Jared; Yet, Shaw-Fang; Perrella, Mark A; Pratt, Richard E; Dzau, Victor J; Melo, Luis G

2006-02-01

We reported previously that predelivery of the anti-oxidant gene heme oxygenase-1 (HO-1) to the heart by adeno associated virus (AAV) markedly reduces injury after acute myocardial infarction (MI). However, the effect of HO-1 gene delivery on postinfarction recovery has not been investigated. In the current study, we assessed the effect of HO-1 gene delivery on post-MI left ventricle (LV) remodeling and function using echocardiographic imaging and histomorphometric approaches. Two groups of Sprague-Dawley rats were injected with 4 x 10(11) particles of AAV-LacZ (control) or AAV-hHO-1 in the LV wall. Eight wk after gene transfer, the animals were subjected to 30 min of ischemia by ligation of left anterior descending artery (LAD) followed by reperfusion. Echocardiographic measurements were obtained in a blinded fashion prior and at 1.5 and 3 months after I/R. Ejection fraction (EF) was reduced by 13% and 40% in the HO-1 and LacZ groups, respectively at 1.5 months after MI. Three months after MI, EF recovered fully in the HO-1, but only partially in the LacZ-treated animals. Post-MI LV dimensions were markedly increased and the anterior wall was markedly thinned in the LacZ-treated animals compared with the HO-1-treated animals. Significant myocardial scarring and fibrosis were observed in the LacZ-group in association with elevated levels of interstitial collagen I and III and MMP-2 activity. Post-MI myofibroblast accumulation was reduced in the HO-1-treated animals, and retroviral overexpression of HO-1 reduced proliferation of isolated cardiac fibroblasts. Our data indicate that rAAV-HO-1 gene transfer markedly reduces fibrosis and ventricular remodeling and restores LV function and chamber dimensions after myocardial infarction.

Isocyanides inhibit human heme oxygenases at the verdoheme stage.

PubMed

Evans, John P; Kandel, Sylvie; Ortiz de Montellano, Paul R

2009-09-22

Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, heme oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps to protect cancer cells from anticancer agents, while HOs in fungal pathogens, such as Candida albicans, function as the primary means of iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. In this study, we have examined the equilibrium binding of three isocyanides, isopropyl, n-butyl, and benzyl, to the two major human HO isoforms (hHO-1 and hHO-2), Candida albicans HO (CaHmx1), and human cytochrome P450 CYP3A4 using electronic absorption spectroscopy. Isocyanides coordinate to both ferric and ferrous HO-bound heme, with tighter binding by the more hydrophobic isocyanides and 200-300-fold tighter binding to the ferrous form. Benzyl isocyanide was the strongest ligand to ferrous heme in all the enzymes. Because the dissociation constants (KD) of the ligands for ferrous heme-hHO-1 were below the limit of accuracy for equilibrium titrations, stopped-flow kinetic experiments were used to measure the binding parameters of the isocyanides to ferrous hHO-1. Steady-state activity assays showed that benzyl isocyanide was the most potent uncompetitive inhibitor with respect to heme with a KI = 0.15 microM for hHO-1. Importantly, single turnover assays revealed that the reaction was completely stopped by coordination of the isocyanide to the verdoheme intermediate rather than to the ferric heme complex. Much tighter binding of the inhibitor to the verdoheme intermediate differentiates it from inhibition of, for example, CYP3A4 and offers a possible route to more selective inhibitor design.

Isocyanides Inhibit Human Heme Oxygenases at the Verdoheme Stage†

PubMed Central

Evans, John P.; Kandel, Sylvie; Ortiz de Montellano, Paul R.

2010-01-01

Heme oxygenases (HO) catalyze the oxidative cleavage of heme to generate biliverdin, CO, and free iron. In humans, heme oxygenase-1 (hHO-1) is overexpressed in tumor tissues, where it helps to protect cancer cells from anticancer agents, while HOs in fungal pathogens, such as Candida albicans, function as the primary means of iron acquisition. Thus, HO can be considered a potential therapeutic target for certain diseases. In this study, we have examined the equilibrium binding of three isocyanides; isopropyl, n-butyl, and benzyl, to the two major human HO isoforms (hHO-1 and hHO-2), Candida albicans HO (CaHmx1), and human cytochrome P450 CYP3A4 using electronic absorption spectroscopy. Isocyanides coordinate to both ferric and ferrous HO-bound heme, with tighter binding by the more hydrophobic isocyanides, and 200-300-fold tighter binding to the ferrous form. Benzyl isocyanide was the strongest ligand to ferrous heme in all the enzymes. Because the dissociation constants (KD) of the ligands for ferrous heme-hHO-1 were below the limit of accuracy for equilibrium titrations, stopped-flow kinetic experiments were used to measure the binding parameters of the isocyanides to ferrous hHO-1. Steady-state activity assays showed that benzyl isocyanide was the most potent uncompetitive inhibitor with respect to heme with a KI = 0.15 μM for hHO-1. Importantly, single turnover assays revealed that the reaction was completely stopped by coordination of the isocyanide to the verdoheme intermediate rather than to the ferric heme complex. Much tighter binding of the inhibitor to the verdoheme intermediate differentiates it from inhibition of, for example, CYP3A4 and offers a possible route to more selective inhibitor design. PMID:19694439

HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study.

PubMed

Jiang, Yibo; Chen, Lijuan; Tang, Yaoliang; Ma, Genshan; Shen, Chengxing; Qi, Chunmei; Zhu, Qi; Yao, Yuyu; Liu, Naifeng

2010-05-01

To determine the effect of intracoronary transfer of superparamagnetic iron oxide (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was assayed and supernatant cytokine concentrations were measured in BMSCs that underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD occlusion followed by 1 h reperfusion were randomly allocated to receive intracoronary saline (control), 1 x 10(7) SPIO-labeled BMSCs transfected with pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1-hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI and postmortem histological analysis were made at 1 week or 3 months thereafter. Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant VEGF significantly increased while TNF-alpha and IL-6 significantly reduced in HO-1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs group at 1 week post transplantation (all p < 0.05). Signal voids induced by the SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but not at 3 months post transplantation and the extent of the hypointense signal was the highest in HO-1-BMSCs group, and histological analysis showed that signal voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs. Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1-BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the beneficial effects of BMSCs on improving cardiac function in this model.

Generation and characterization of human heme oxygenase-1 transgenic pigs.

PubMed

Yeom, Hye-Jung; Koo, Ok Jae; Yang, Jaeseok; Cho, Bumrae; Hwang, Jong-Ik; Park, Sol Ji; Hurh, Sunghoon; Kim, Hwajung; Lee, Eun Mi; Ro, Han; Kang, Jung Taek; Kim, Su Jin; Won, Jae-Kyung; O'Connell, Philip J; Kim, Hyunil; Surh, Charles D; Lee, Byeong-Chun; Ahn, Curie

2012-01-01

Xenotransplantation using transgenic pigs as an organ source is a promising strategy to overcome shortage of human organ for transplantation. Various genetic modifications have been tried to ameliorate xenograft rejection. In the present study we assessed effect of transgenic expression of human heme oxygenase-1 (hHO-1), an inducible protein capable of cytoprotection by scavenging reactive oxygen species and preventing apoptosis caused by cellular stress during inflammatory processes, in neonatal porcine islet-like cluster cells (NPCCs). Transduction of NPCCs with adenovirus containing hHO-1 gene significantly reduced apoptosis compared with the GFP-expressing adenovirus control after treatment with either hydrogen peroxide or hTNF-α and cycloheximide. These protective effects were diminished by co-treatment of hHO-1 antagonist, Zinc protoporphyrin IX. We also generated transgenic pigs expressing hHO-1 and analyzed expression and function of the transgene. Human HO-1 was expressed in most tissues, including the heart, kidney, lung, pancreas, spleen and skin, however, expression levels and patterns of the hHO-1 gene are not consistent in each organ. We isolate fibroblast from transgenic pigs to analyze protective effect of the hHO-1. As expected, fibroblasts derived from the hHO-1 transgenic pigs were significantly resistant to both hydrogen peroxide damage and hTNF-α and cycloheximide-mediated apoptosis when compared with wild-type fibroblasts. Furthermore, induction of RANTES in response to hTNF-α or LPS was significantly decreased in fibroblasts obtained from the hHO-1 transgenic pigs. These findings suggest that transgenic expression of hHO-1 can protect xenografts when exposed to oxidative stresses, especially from ischemia/reperfusion injury, and/or acute rejection mediated by cytokines. Accordingly, hHO-1 could be an important candidate molecule in a multi-transgenic pig strategy for xenotransplantation.

L-ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1.

PubMed

Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien; Lin, Chih-Hung; Lai, Chien-Cheng; Wang, Jia-Yi

2012-12-01

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of l-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measured using the fluorochrome 2',7'-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

Risk Factors for the Development of Heterotopic Ossification in Seriously Burned Adults: A NIDRR Burn Model System Database Analysis

PubMed Central

Levi, Benjamin; Jayakumar, Prakash; Giladi, Avi; Jupiter, Jesse B.; Ring, David C.; Kowalske, Karen; Gibran, Nicole S.; Herndon, David; Schneider, Jeffrey C.; Ryan, Colleen M.

2015-01-01

Purpose Heterotopic ossification (HO) is a debilitating complication of burn injury; however, incidence and risk factors are poorly understood. In this study we utilize a multicenter database of adults with burn injuries to identify and analyze clinical factors that predict HO formation. Methods Data from 6 high-volume burn centers, in the Burn Injury Model System Database, were analyzed. Univariate logistic regression models were used for model selection. Cluster-adjusted multivariate logistic regression was then used to evaluate the relationship between clinical and demographic data and the development of HO. Results Of 2,979 patients in the database with information on HO that addressed risk factors for development of HO, 98 (3.5%) developed HO. Of these 98 patients, 97 had arm burns, and 96 had arm grafts. Controlling for age and sex in a multivariate model, patients with >30% total body surface area (TBSA) burn had 11.5x higher odds of developing HO (p<0.001), and those with arm burns that required skin grafting had 96.4x higher odds of developing HO (p=0.04). For each additional time a patient went to the operating room, odds of HO increased 30% (OR 1.32, p<0.001), and each additional ventilator day increase odds 3.5% (OR 1.035, p<0.001). Joint contracture, inhalation injury, and bone exposure did not significantly increase odds of HO. Conclusion Risk factors for HO development include >30% TBSA burn, arm burns, arm grafts, ventilator days, and number of trips to the operating room. Future studies can use these results to identify highest-risk patients to guide deployment of prophylactic and experimental treatments. PMID:26496115

Test Plans and Procedures for the Baseline SAF for BDS-D Sites (ModSAF). Volume 2

DTIC Science & Technology

1993-12-20

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Strategic Studies Quarterly. Volume 2, Number 3, Fall 2008

DTIC Science & Technology

2008-01-01

Managing Editor Betty R. Littlejohn, Editorial Assistant Jerry L. Gantt, Content Editor Sherry Terrell , Editorial Assistant Steven C. Garst...factsheet.asp?id=107 . Ibid. 9. Lt Col Sebastian M. Convertino II, CDR Lou Anne DeMattei, and Lt Col Tammy Knierim, Flying and Fighting in...PhD, Editor-in-Chief L. Tawanda Eaves, Managing Editor Betty R. Littlejohn, Editorial Assistant Jerry L. Gantt, Content Editor Sherry Terrell

PREFACE: Many-body correlations from dilute to dense nuclear systems

NASA Astrophysics Data System (ADS)

Otsuka, Takaharu; Urban, Michael; Yamada, Taiichi

2011-09-01

The International EFES-IN2P3 conference on "Many body correlations from dilute to dense nuclear systems" was held at the Institut Henri Poincaré (IHP), Paris, France, from 15-18 February 2011, on the occasion of the retirement of our colleague Peter Schuck. Correlations play a decisive role in various many-body systems such as nuclear systems, condensed matter and quantum gases. Important examples include: pairing correlations (Cooper pairs) which give rise to nuclear superfluidity (analogous to superconductivity in condensed matter); particle-hole (RPA) correlations in the description of the ground state beyond mean-field theory; clusters; and α-particle correlations in certain nuclei. Also, the nucleons themselves can be viewed as clusters of three quarks. During the past few years, researchers have started to study how the character of these correlations changes with the variation of the density. For instance, the Cooper pairs in dense matter can transform into a Bose-Einstein condensate (BEC) of true bound states at low density (this is the BCS-BEC crossover studied in ultracold Fermi gases). Similar effects play a role in neutron matter at low density, e.g., in the "neutron skin" of exotic nuclei. The α-cluster correlation becomes particularly important at lower density, such as in the excited states of some nuclei (e.g., the α-condensate-like structure in the Hoyle state of 12C) or in the formation of compact stars. In addition to nuclear physics, topics from astrophysics (neutron stars), condensed matter, and quantum gases were discussed in 48 talks and 19 posters, allowing the almost 90 participants from different communities to exchange their ideas, experiences and methods. The conference dinner took place at the Musée d'Orsay, and all the participants enjoyed the very pleasant atmosphere. One session of the conference was dedicated to the celebration of Peter's retirement. We would like to take this opportunity to wish Peter all the best and we hope that he will continue his scientific work full of creative and original ideas. We would like to thank all those who helped to make the conference a success: Nguyen van Giai, S Fujii, J Margueron, K Hagino, and Y Kanada-En'yo for their help with the organization; the advisory committee for suggesting invited speakers; V Frois for her administrative help; L Petizon for the website; and the director of IPN Orsay, F Azaiez, for his support. We are indebted to IHP for providing the lecture hall free of charge, and we acknowledge the financial support from JSPS through its EFES core-to-core program, from CNRS (IN2P3 and INP), and from LIA France-Japon. Last but not least, we are grateful to all of the participants for making the conference exciting and successful. Takaharu Otsuka, Michael Urban, Taiichi YamadaEditors of the proceedings

The cumulative influence of hyperoxia and hypercapnia on blood oxygenation and R2*

PubMed Central

Faraco, Carlos C; Strother, Megan K; Siero, Jeroen CW; Arteaga, Daniel F; Scott, Allison O; Jordan, Lori C; Donahue, Manus J

2015-01-01

Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R2*, and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3 T; TE/TR=35/2,000 ms; spatial resolution=3 × 3 × 3.5 mm3) in healthy volunteers (n=12; age=29±4.1 years) breathing (i) room air (RA), (ii) normocapnic–hyperoxia (95% O2/5% N2, HO), (iii) hypercapnic–normoxia (5% CO2/21% O2/74% N2, HC-NO), and (iv) hypercapnic–hyperoxia (5% CO2/95% O2, HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O2. T2-relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood–water R2*, and tissue–water R2*. In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA=0.011±0.007; HC-NO/RA=0.014±0.004; HC-HO/HO=0.020±0.008; and HC-HO/RA=0.035±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R2* are altered during hyperoxia. PMID:26174329

Loss of heme oxygenase-1 accelerates mesodermal gene expressions during embryoid body development from mouse embryonic stem cells.

PubMed

Lai, Yan-Liang; Lin, Chen-Yu; Jiang, Wei-Cheng; Ho, Yen-Chun; Chen, Chung-Huang; Yet, Shaw-Fang

2018-05-01

Heme oxygenase (HO)-1 is an inducible stress response protein and well known to protect cells and tissues against injury. Despite its important function in cytoprotection against physiological stress, the role of HO-1 in embryonic stem cell (ESC) differentiation remains largely unknown. We showed previously that induced pluripotent stem (iPS) cells that lack HO-1 are more sensitive to oxidant stress-induced cell death and more prone to lose pluripotent markers upon LIF withdrawal. To elucidate the role of HO-1 in ESC differentiation and to rule out the controversy of potential gene flaws in iPS cells, we derived and established mouse HO-1 knockout ESC lines from HO-1 knockout blastocysts. Using wild type D3 and HO-1 knockout ESCs in the 3-dimensional embryoid body (EB) differentiation model, we showed that at an early time point during EB development, an absence of HO-1 led to enhanced ROS level, concomitant with increased expressions of master mesodermal regulator brachyury and endodermal marker GATA6. In addition, critical smooth muscle cell (SMC) transcription factor serum response factor and its coactivator myocardin were enhanced. Furthermore, HO-1 deficiency increased Smad2 in ESCs and EBs, revealing a role of HO-1 in controlling Smad2 level. Smad2 not only mediates mesendoderm differentiation of mouse ESCs but also SMC development. Collectively, loss of HO-1 resulted in higher level of mesodermal and SMC regulators, leading to accelerated and enhanced SMC marker SM α-actin expression. Our results reveal a previously unrecognized function of HO-1 in regulating SMC gene expressions during ESC-EB development. More importantly, our findings may provide a novel strategy in enhancing ESC differentiation toward SMC lineage. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Adenovirus-delivered GFP-HO-1C[INCREMENT]23 attenuates blood-spinal cord barrier permeability after rat spinal cord contusion.

PubMed

Chang, Sheng; Bi, Yunlong; Meng, Xiangwei; Qu, Lin; Cao, Yang

2018-03-21

The blood-spinal cord barrier (BSCB) plays a key role in maintaining the microenvironment and is primarily composed of tight junction proteins and nonfenestrated capillary endothelial cells. After injury, BSCB damage results in increasing capillary permeability and release of inflammatory factors. Recent studies have reported that haem oxygenase-1 (HO-1) fragments lacking 23 amino acids at the C-terminus (HO-1C[INCREMENT]23) exert novel anti-inflammatory and antioxidative effects in vitro. However, no study has identified the role of HO-1C[INCREMENT]23 in vivo. We aimed to investigate the protective effects of HO-1C[INCREMENT]23 on the BSCB after spinal cord injury (SCI) in a rat model. Here, adenoviral HO-1C[INCREMENT]23 (Ad-GFP-HO-1C[INCREMENT]23) was intrathecally injected into the 10th thoracic spinal cord segment (T10) 7 days before SCI. In addition, nuclear and cytoplasmic extraction and immunofluorescence staining of HO-1 were used to examine the effect of Ad-GFP-HO-1C[INCREMENT]23 on HO-1 nuclear translocation. Evan's blue staining served as an index of capillary permeability and was detected by fluorescence microscopy at 633 nm. Western blotting was also performed to detect tight junction protein expression. The Basso, Beattie and Bresnahan score was used to evaluate kinematic functional recovery through the 28th day after SCI. In this study, the Ad-GFP-HO-1C[INCREMENT]23 group showed better kinematic functional recovery after SCI than the Ad-GFP and Vehicle groups, as well as smaller reductions in TJ proteins and capillary permeability compared with those in the Ad-GFP and Vehicle groups. These findings indicated that Ad-GFP-HO-1C[INCREMENT]23 might have a potential therapeutic effect that is mediated by its protection of BSCB integrity.

Establishing the Dependence of [HO2]/[OH] on Temperature, Halogen Loading, O3, and NO(x) Based on in Situ Measurements from the NASA ER-2

NASA Technical Reports Server (NTRS)

Lanzendorf, E. J.; Hanisco, T. F.; Wennberg, P. O.; Cohen, R. C.; Stimpfle, R. M.; Anderson, J. G.; Gao, R. S.; Margitan, J. J.; Bui, T. P.

2001-01-01

In situ observations of OH and HO2 from the Airborne Southern Hemisphere Ozone Experiment/Measurements for Assessing the Effects of Stratospheric Aircraft (ASHOE/MAESA), Stratospheric TRacers of Atmospheric Transport (STRAT), and Polar Ozone Loss in the Arctic Region in Summer (POLARIS) NASA ER-2 field campaigns are used to examine the partitioning of HO(x) in the lower stratosphere (tropopause to approx.21 km) and upper troposphere (approx.10 km to tropopause). These measurements span a latitude range from 70degS to 90degN and a variety of atmospheric conditions as a result of seasonal changes and altitude. The response of the observed [HO2]/[OH] to changes in temperature, [03], [CO], [NO], [CIO], and [BrO] is investigated. The measured ratio is accurately described (approx.+/-10%) by a steady-state model constrained by the measured mixing ratios of O3, CO, NO, CIO, and BrO, where the model is valid for conditions of HO(x) cycling much faster than HO(x) production and loss. The concentration of HO2 depends on [OH], which, to first order, has been observed to be a simple function of the solar zenith angle in the lower stratosphere. The partitioning between OH and HO2 is controlled by the local chemistry between the HO, radicals and O3, CO, NO, CIO, and BrO. The response of [HO(x)] to changes in [NO(x)] and [O3] is demonstrated. Further observations are necessary to illustrate the response of HO(x) to changes in halogen concentrations. A quantitative understanding of [HO2]/[OH] is important, since many of the reactions that control this ratio are directly involved in catalytic removal of O3 in the lower stratosphere and production of O3 in the upper troposphere.

Synergistic effect of Fe2O3/Ho2O3 Co-modified 2D-titanate heterojunctions on enhanced photocatalytic degradation

NASA Astrophysics Data System (ADS)

Zhao, Xiaona; Liu, Xinzhao; Lu, Dingze; Wu, Pei; Yan, Qiuyang; Liu, Min; Fang, Pengfei

2017-01-01

TiO2-based nanosheets (TNSs) co-modified by Fe2O3 and Ho2O3 were synthesized by one-pot hydrothermal method using Fe(NO3)3 and Ho(NO3)3 as precursors compositing with TiO2. The Fe2O3/Ho2O3-TNSs heterojunctions possessed a thickness of approximately 3-4 nm, large specific surface area of 210-310 cm2/g, with Fe2O3 and Ho2O3 nanoparticles highly dispersed over the surface of the nanosheets. The crystallization of the samples gradually increased with the amount of Fe2O3 nanoparticles, which was confirmed by the XRD, BET and Raman spectra, indicating that Ho2O3 and Fe2O3 influenced the crystallinity and structure evolution of the TNSs, besides, led to an improved the visible-light absorption. Surface photocurrent and fluorescence spectral studies revealed that the photo-generated charge carrier separation efficiency could be efficiently improved by an appropriate amount of modification. The Fe2O3/Ho2O3-TNSs exhibited synergistic effect on photocatalytic degradation of RhB as well as MO under visible light. The highest efficiency was obtained by 0.05%-Fe2O3/Ho2O3-TNSs (Fe:Ho:Ti = 0.05:1:100), which was 8.86 and 6.72 times than that of individual 1.0%-Ho2O3-TNSs (Ho:Ti = 1:100) and 0.05%-Fe2O3-TNSs (Fe:Ti = 0.05:100), respectively. The possible mechanism for enhanced visible-light-induced photocatalytic activity was proposed. Ho2O3 introduced in the photocatalysts may act as the hole capture while Fe2O3 may share the same Fermi levels with TNSs and serve as the electron capture center in the n-n-p system, which reduced the recombination rate of photo-induced electron-hole pairs.

Clinical effects of transcatheter hepatic arterial embolization with holmium-166 poly(l-lactic acid) microspheres in healthy pigs

PubMed Central

Nijsen, J. F. W.; de Wit, T. C.; Seppenwoolde, J. H.; Krijger, G. C.; Seevinck, P. R.; Huisman, A.; Zonnenberg, B. A.; van den Ingh, T. S. G. A. M.; van het Schip, A. D.

2008-01-01

Purpose The aim of this study is to evaluate the toxicity of holmium-166 poly(l-lactic acid) microspheres administered into the hepatic artery in pigs. Methods Healthy pigs (20–30 kg) were injected into the hepatic artery with holmium-165-loaded microspheres (165HoMS; n = 5) or with holmium-166-loaded microspheres (166HoMS; n = 13). The microspheres’ biodistribution was assessed by single-photon emission computed tomography and/or MRI. The animals were monitored clinically, biochemically, and (166HoMS group only) hematologically over a period of 1 month (165HoMS group) or over 1 or 2 months (166HoMS group). Finally, a pathological examination was undertaken. Results After microsphere administration, some animals exhibited a slightly diminished level of consciousness and a dip in appetite, both of which were transient. Four lethal adverse events occurred in the 166HoMS group due either to incorrect administration or comorbidity: inadvertent delivery of microspheres into the gastric wall (n = 2), preexisting gastric ulceration (n = 1), and endocarditis (n = 1). AST levels were transitorily elevated post-166HoMS administration. In the other blood parameters, no abnormalities were observed. Nuclear scans were acquired from all animals from the 166HoMS group, and MRI scans were performed if available. In pigs from the 166HoMS group, atrophy of one or more liver lobes was frequently observed. The actual radioactivity distribution was assessed through ex vivo 166mHo measurements. Conclusion It can be concluded that the toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with 166HoMS in amounts corresponding with liver-absorbed doses of over 100 Gy, if correctly administered, is not associated with clinically relevant side effects. This result offers a good perspective for upcoming patient trials. PMID:18330569

Iron depletion in HCT116 cells diminishes the upregulatory effect of phenethyl isothiocyanate on heme oxygenase-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bolloskis, Michael P.; Carvalho, Fabiana P.; Loo, George, E-mail: g_loo@uncg.edu

Some of the health-promoting properties of cruciferous vegetables are thought to be partly attributed to isothiocyanates. These phytochemicals can upregulate the expression of certain cytoprotective stress genes, but it is unknown if a particular nutrient is involved. Herein, the objective was to ascertain if adequate iron is needed for enabling HCT116 cells to optimally express heme oxygenase-1 (HO-1) when induced by phenethyl isothiocyanate (PEITC). PEITC increased HO-1 expression and also nuclear translocation of Nrf2, which is a transcription factor known to activate the HO-1 gene. However, in HCT116 cells that were made iron-deficient by depleting intracellular iron with deferoxamine (DFO),more » PEITC was less able to increase HO-1 expression and nuclear translocation of Nrf2. These suppressive effects of DFO were overcome by replenishing the iron-deficient cells with the missing iron. To elucidate these findings, it was found that PEITC-induced HO-1 upregulation can be inhibited with thiol antioxidants (glutathione and N-acetylcysteine). Furthermore, NADPH oxidase inhibitors (diphenyleneiodonium and apocynin) and a superoxide scavenger (Tiron) each inhibited PEITC-induced HO-1 upregulation. In doing so, diphenyleneiodonium was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf2. Collectively, the results imply that the HO-1 upregulation by PEITC involves an iron-dependent, oxidant signaling pathway. Therefore, it is concluded that ample iron is required to enable PEITC to fully upregulate HO-1 expression in HCT116 cells. As such, it is conceivable that iron-deficient individuals may not reap the full health benefits of eating PEITC-containing cruciferous vegetables that via HO-1 may help protect against multiple chronic diseases. - Highlights: • PEITC increased HO-1 expression in HCT116 cells. • PEITC-induced HO-1 upregulation was impaired in iron-depleted HCT116 cells. • Impairment of PEITC-induced HO-1 upregulation was reversible with iron restoration. • PEITC increased nuclear expression of Nrf2 but not in iron-depleted cells. • NADPH oxidase inhibitors inhibited PEITC-induced HO-1 upregulation.« less

Structure, upconversion photoluminescence, and dielectric properties of Ho{sup 3+}- and Yb{sup 3+}-codoped tetragonal tungsten bronze Sr{sub 4}La{sub 2}Ti{sub 4}Nb{sub 6}O{sub 30}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, T., E-mail: weitong.nju@gmail.com; Li, C.P.; Zhou, Q.J.

2015-04-15

Highlights: • TTB-type SLTN: Ho-Ybx with space group P4/mbm was determined. • UC photoluminescence of SLTN: Ho-Ybx ceramics was first reported. • Bright UC green emission was observed at room temperature. • Two-photon energy transfer process was confirmed for the UC processes. • Temperature stability of dielectric permittivity was improved for SLTN: Ho-Ybx. - Abstract: Ho{sup 3+}- and Yb{sup 3+}-codoped Sr{sub 4}La{sub 2}Ti{sub 4}Nb{sub 6}O{sub 30} (Sr{sub 4}La{sub 1.94–x}Ho{sub 0.06}Yb{sub x}Ti{sub 4}Nb{sub 6}O{sub 30}, abbreviated as SLTN: Ho-Ybx) ceramics have been synthesized, and their structural, up-conversion (UC) photoluminescence, and dielectric properties have been carefully investigated. Through Rietveld structural refinement, SLTN:more » Ho-Ybx samples are determined as single tetragonal tungsten bronze (TTB) phase with space group P4/mbm in which larger Sr{sup 2+} ions fill the A{sub 2}-sites, relative smaller La{sup 3+}, Ho{sup 3+}, and Yb{sup 3+} ions occupy the A{sub 1}-sites, while Ti{sup 4+} and Nb{sup 4+} ions fill the B-sites. Under 980 nm near infrared (NIR) excitation, bright UC green emission, relatively weak red and near-infrared (NIR) emissions, originating from {sup 5}F{sub 4}/{sup 5}S{sub 2} → {sup 5}I{sub 8}, {sup 5}F{sub 5} → {sup 5}I{sub 8}, and {sup 5}F{sub 4}/{sup 5}S{sub 2} → {sup 5}I{sub 7} transitions of Ho{sup 3+} ions, are confirmed for SLTN: Ho-Ybx. Two-photon energy transfer process is proved through pumping laser power dependence of emission intensity measurement. Furthermore, the influence of Ho{sup 3+}- and Yb{sup 3+}- ions on the dielectric properties of SLTN: Ho-Ybx is also investigated and the temperature stability of dielectric permittivity is improved.« less

Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2 are dynamically disordered and exhibit redox-dependent interaction with heme

DOE PAGES

Bagai, Ireena; Sarangi, Ritimukta; Fleischhacker, Angela S.; ...

2015-05-05

Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O₂₋ and NADPH-cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO through a process in which the heme participates both as a prosthetic group and as a substrate. Mammals contain two isoforms of this enzyme, HO2 and HO1, which share the same α-helical fold forming the catalytic core and heme binding site, as well as a membrane spanning helix at their C-termini. However, unlike HO1, HO2 has an additional 30-residue N-terminus as well as two cysteine-proline sequences near the C-terminus that reside in heme regulatory motifs (HRMs).more » While the role of the additional N-terminal residues of HO2 is not yet understood, the HRMs have been proposed to reversibly form a thiol/disulfide redox switch that modulates the affinity of HO2 for ferric heme as a function of cellular redox poise. To further define the roles of the N- and C-terminal regions unique to HO2, we used multiple spectroscopic techniques to characterize these regions of the human HO2. Nuclear magnetic resonance spectroscopic experiments with HO2 demonstrate that, when the HRMs are in the oxidized state (HO2 O), both the extra N-terminal and the C-terminal HRM-containing regions are disordered. However, protein NMR experiments illustrate that, under reducing conditions, the C-terminal region gains some structure as the Cys residues in the HRMs undergo reduction (HO2 R) and, in experiments employing a diamagnetic protoporphyrin, suggest a redox-dependent interaction between the core and the HRM domains. Further, electron nuclear double resonance and X-ray absorption spectroscopic studies demonstrate that, upon reduction of the HRMs to the sulfhydryl form, a cysteine residue from the HRM region ligates to a ferric heme. Taken together with EPR measurements, which show the appearance of a new low-spin heme signal in reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts with a second bound heme.« less

Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Su Jin; Kang, Hyung Kyung; Song, Dong Keun

Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner.more » PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.« less

Spectroscopic studies reveal that the heme regulatory motifs of heme oxygenase-2 are dynamically disordered and exhibit redox-dependent interaction with heme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bagai, Ireena; Sarangi, Ritimukta; Fleischhacker, Angela S.

Heme oxygenase (HO) catalyzes a key step in heme homeostasis: the O₂₋ and NADPH-cytochrome P450 reductase-dependent conversion of heme to biliverdin, Fe, and CO through a process in which the heme participates both as a prosthetic group and as a substrate. Mammals contain two isoforms of this enzyme, HO2 and HO1, which share the same α-helical fold forming the catalytic core and heme binding site, as well as a membrane spanning helix at their C-termini. However, unlike HO1, HO2 has an additional 30-residue N-terminus as well as two cysteine-proline sequences near the C-terminus that reside in heme regulatory motifs (HRMs).more » While the role of the additional N-terminal residues of HO2 is not yet understood, the HRMs have been proposed to reversibly form a thiol/disulfide redox switch that modulates the affinity of HO2 for ferric heme as a function of cellular redox poise. To further define the roles of the N- and C-terminal regions unique to HO2, we used multiple spectroscopic techniques to characterize these regions of the human HO2. Nuclear magnetic resonance spectroscopic experiments with HO2 demonstrate that, when the HRMs are in the oxidized state (HO2 O), both the extra N-terminal and the C-terminal HRM-containing regions are disordered. However, protein NMR experiments illustrate that, under reducing conditions, the C-terminal region gains some structure as the Cys residues in the HRMs undergo reduction (HO2 R) and, in experiments employing a diamagnetic protoporphyrin, suggest a redox-dependent interaction between the core and the HRM domains. Further, electron nuclear double resonance and X-ray absorption spectroscopic studies demonstrate that, upon reduction of the HRMs to the sulfhydryl form, a cysteine residue from the HRM region ligates to a ferric heme. Taken together with EPR measurements, which show the appearance of a new low-spin heme signal in reduced HO2, it appears that a cysteine residue(s) in the HRMs directly interacts with a second bound heme.« less

The induction of heme oxygenase-1 suppresses heat shock protein 90 and the proliferation of human breast cancer cells through its byproduct carbon monoxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Wen-Ying; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Chen, Yen-Chou

2014-01-01

Heme oxygenase (HO)-1 is an oxidative stress-response enzyme which catalyzes the degradation of heme into bilirubin, ferric ion, and carbon monoxide (CO). Induction of HO-1 was reported to have antitumor activity; the inhibitory mechanism, however, is still unclear. In the present study, we found that treatment with [Ru(CO){sub 3}Cl{sub 2}]{sub 2} (RuCO), a CO-releasing compound, reduced the growth of human MCF7 and MDA-MB-231 breast cancer cells. Analysis of growth-related proteins showed that treatment with RuCO down-regulated cyclinD1, CDK4, and hTERT protein expressions. Interestingly, RuCO treatment resulted in opposite effects on wild-type and mutant p53 proteins. These results were similar tomore » those of cells treated with geldanamycin (a heat shock protein (HSP)90 inhibitor), suggesting that RuCO might affect HSP90 activity. Moreover, RuCO induced mutant p53 protein destabilization accompanied by promotion of ubiquitination and proteasome degradation. The induction of HO-1 by cobalt protoporphyrin IX (CoPP) showed consistent results, while the addition of tin protoporphyrin IX (SnPP), an HO-1 enzymatic inhibitor, diminished the RuCO-mediated effect. RuCO induction of HO-1 expression was reduced by a p38 mitogen-activated protein kinase inhibitor (SB203580). Additionally, treatment with a chemopreventive compound, curcumin, induced HO-1 expression accompanied with reduction of HSP90 client protein expression. The induction of HO-1 by curcumin inhibited 12-O-tetradecanoyl-13-acetate (TPA)-elicited matrix metalloproteinase-9 expression and tumor invasion. In conclusion, we provide novel evidence underlying HO-1's antitumor mechanism. CO, a byproduct of HO-1, suppresses HSP90 protein activity, and the induction of HO-1 may possess potential as a cancer therapeutic. - Highlights: • CO and HO-1 inhibited the growth of human breast cancer cells. • CO and HO-1 attenuated HSP90 and its client proteins expression. • CO induced mutant p53 protein ubiquitination and degradation. • Curcumin induced HO-1 expression and attenuated HSP90's client proteins expression.« less

L-Ascorbate attenuates methamphetamine neurotoxicity through enhancing the induction of endogenous heme oxygenase-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ya-Ni; Wang, Jiz-Yuh; Lee, Ching-Tien

Methamphetamine (METH) is a drug of abuse which causes neurotoxicity and increased risk of developing neurodegenerative diseases. We previously found that METH induces heme oxygenase (HO)-1 expression in neurons and glial cells, and this offers partial protection against METH toxicity. In this study, we investigated the effects of L-ascorbate (vitamin C, Vit. C) on METH toxicity and HO-1 expression in neuronal/glial cocultures. Cell viability and damage were evaluated by 3-(4,5-dimethylthianol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release, respectively. Neuronal and glial localization of HO-1 were identified by double immunofluorescence staining. Reactive oxygen species (ROS) production was measuredmore » using the fluorochrome 2′,7′-dichlorofluorescin diacetate. HO-1 mRNA and protein expression were examined by RT-qPCR and Western blotting, respectively. Results show that Vit. C induced HO-1 mRNA and protein expressions in time- and concentration-dependent manners. Inhibition of p38 mitogen-activated protein kinase (MAPK) but not extracellular signal-regulated kinase (ERK) significantly blocked induction of HO-1 by Vit. C. HO-1 mRNA and protein expressions were significantly elevated by a combination of Vit. C and METH, compared to either Vit. C or METH alone. Pretreatment with Vit. C enhanced METH-induced HO-1 expression and attenuated METH-induced ROS production and neurotoxicity. Pharmacological inhibition of HO activity abolished suppressive effects of Vit. C on METH-induced ROS production and attenuated neurotoxicity. We conclude that induction of HO-1 expression contributes to the attenuation of METH-induced ROS production and neurotoxicity by Vit. C. We suggest that HO-1 induction by Vit. C may serve as a strategy to alleviate METH neurotoxicity. -- Highlights: ► Besides the anti-oxidant effect, Vit. C also induces HO-1 expression in brain cells. ► Vit. C reduces METH neurotoxicity and ROS production by upregulating HO-1 expression. ► These results suggest a therapeutic potential for Vit. C in treating METH abusers.« less

Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model.

PubMed

Hinkel, Rabea; Lange, Philipp; Petersen, Björn; Gottlieb, Elena; Ng, Judy King Man; Finger, Stefanie; Horstkotte, Jan; Lee, Seungmin; Thormann, Michael; Knorr, Maike; El-Aouni, Chiraz; Boekstegers, Peter; Reichart, Bruno; Wenzel, Philip; Niemann, Heiner; Kupatt, Christian

2015-07-14

Heme oxygenase-1 (HO-1) is an inducible stress-responsive enzyme converting heme to bilirubin, carbon monoxide, and free iron, which exerts anti-inflammatory and antiapoptotic effects. Although efficient cardioprotection after HO-1 overexpression has been reported in rodents, its role in attenuating post-ischemic inflammation is unclear. This study assessed the efficacy of recombinant adenoassociated virus (rAAV)-encoding human heme oxygenase-1 (hHO-1) in attenuating post-ischemic inflammation in a murine and a porcine ischemia/reperfusion model. Murine ischemia was induced by 45 min of left anterior descending occlusion, followed by 24 h of reperfusion and functional as well as fluorescent-activated cell sorting analysis. Porcine hearts were subjected to 60 min of ischemia and 24h of reperfusion before hemodynamic and histologic analyses were performed. Human microvascular endothelial cells transfected with hHO-1 displayed an attenuated interleukin-6 and intercellular adhesion molecule 1 expression, resulting in reduced monocytic THP-1 cell recruitment in vitro. In murine left anterior descending occlusion and reperfusion, the post-ischemic influx of CD45(+) leukocytes, Ly-6G(+) neutrophils, and Ly-6C(high) monocytes was further exacerbated in HO-1-deficient hearts and reversed by rAAV.hHO-1 treatment. Conversely, in our porcine model of ischemia, the post-ischemic influx of myeloperoxidase-positive neutrophils and CD14(+) monocytes was reduced by 49% and 87% after rAAV.hHO-1 transduction, similar to hHO-1 transgenic pigs. Functionally, rAAV.hHO-1 and hHO-1 transgenic left ventricles displayed a smaller loss of ejection fraction than control animals. Whereas HO-1 deficiency exacerbates post-ischemic cardiac inflammation in mice, hHO-1 gene therapy attenuates inflammation after ischemia and reperfusion in murine and porcine hearts. Regional hHO-1 gene therapy provides cardioprotection in a pre-clinical porcine ischemia/reperfusion model. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Induction of HO-1 by carbon monoxide releasing molecule-2 attenuates thrombin-induced COX-2 expression and hypertrophy in primary human cardiomyocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chien, Peter Tzu-Yu; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan; Lin, Chih-Chung

Carbon monoxide (CO) is one of the cytoprotective byproducts of heme oxygenase (HO)-1 and exerts anti-inflammatory action in various models. However, the detailed mechanisms underlying CO-induced HO-1 expression in primary human cardiomyocytes remain largely unidentified. We used primary left ventricle myocytes as a model and applied CO releasing molecule (CORM)-2 to investigate the relationship of CO and HO-1 expression. We herein used Western blot, real-time PCR, promoter activity and EIA to investigate the role of HO-1 expression protecting against thrombin-mediated responses. We found that thrombin-induced COX-2 expression, PGE{sub 2} release and cardiomyocyte hypertrophy markers (increase in ANF/BNP, α-actin expression andmore » cell surface area) was attenuated by pretreatment with CORM-2 which was partially reversed by hemoglobin (Hb) or ZnPP (an inhibitor of HO-1 activity), suggesting that HO-1/CO system may be of clinical importance to ameliorate heart failure through inhibition of inflammatory responses. CORM-2-induced HO-1 protein expression, mRNA and promoter was attenuated by pretreatment with the inhibitors of Pyk2 (PF431396), PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), p38 (SB202530), JNK1/2 (SP600125), FoxO1 (AS1842856) and Sp1 (mithramycin A). The involvement of these signaling components was further confirmed by transfection with respective siRNAs, consistent with those of pharmacological inhibitors. These results suggested that CORM-2-induced HO-1 expression is mediated through a Pyk2/PDGFR/PI3K/Akt/FoxO1/Sp1-dependent manner and exerts a cytoprotective effect in human cardiomyocytes. - Graphical abstract: In summary, CORM-2 treatment induces Pyk2 transactivated PDGFR, which induces PI3K/Akt/MAPK activation, and then recruits Sp1/Foxo1 transcriptional factors to regulate HO-1 gene expression in primary human cardiomyocytes. - Highlights: • CORM-2 induces HO-1 expression. • Pyk2-dependent PDGFR activates PI3K/Akt/MAPK pathway in CORM-2-induced HO-1 expression. • Transcriptional regulation of HO-1 expression is mediated by Sp1/Foxo1. • CO/HO-1 systems ameliorate thrombin-induced human cardiomyocyte hypertrophy.« less

Heme oxygenase-1-mediated apoptosis under cadmium-induced oxidative stress is regulated by autophagy, which is sensitized by tumor suppressor p53

DOE Office of Scientific and Technical Information (OSTI.GOV)

So, Keum-Young; Oh, Seon-Hee

Heme oxygenase-1 (HO-1) is a stress-inducible cytoprotective enzyme. It is often overexpressed in different types of cancers and promotes cell survival. However, the role of HO-1 and the underlying molecular mechanism of cadmium (Cd)-induced oxidative stress in cancer cells remain undefined. Here we show that the role of HO-1 under Cd-induced oxidative stress is dependent upon autophagy, which is sensitized by the tumor suppressor p53. The sensitivity to Cd was 3.5- and 14-fold higher in p53-expressing YD8 and H460 cells than in p53-null YD10B and H1299 cells, respectively. The levels of p53 in YD8 and H460 cells decreased in a Cd concentration-dependent manner,more » which was inhibited by pretreatment with N-acetylcysteine. In both cell lines, Cd exposure resulted in caspase-3-mediated PARP-1 cleavage and the induction of CHOP, LC3-II, and HO-1, which were limited in YD10B and H1299 cells exposed to high concentrations of Cd. Cd exposure to p53-overexpressing YD10B cells enhanced Cd-induced HO-1 and LC3-II levels, whereas genetic knockdown of p53 in YD8 cells resulted in the suppression of Cd-induced levels of HO-1 and LC3-II, indicating that p53 is required in the sensing of HO-1 and induction of autophagy. The inhibition of autophagy using small interfering RNA (siRNA) for the autophagy-related gene atg5 enhanced HO-1, CHOP, and PARP-1 cleavage induced by Cd. However, transfection with HO-1 siRNA increased Cd-induced LC3-II, and suppressed the expression of CHOP and cleavage of PARP-1. Collectively, the role of HO-1 in apoptosis could be modulated by autophagy, which is sensitized by p53 expression in human cancer cell lines. - Highlights: • Cadmium exposure decreased p53 level, and induced HO-1, apoptosis, and autophagy. • p53 sensitized Cadmium-induced HO-1 and autophagy induction. • Cadmium induced HO-1 under autophagy impairment and increased apoptosis. • Cadmium-induced autophagy was enhanced under HO-1 impaired conditions. • The role of HO-1 in Cadmium-induced apoptosis is modulated by autophagy.« less

1200130

NASA Image and Video Library

2012-03-19

PETER MA, EV74, WEARS A SUIT COVERED WITH SPHERICAL REFLECTORS THAT ENABLE HIS MOTIONS TO BE TRACKED BY THE MOTION CAPTURE SYSTEM. THE HUMAN MODEL IN RED ON THE SCREEN IN THE BACKGROUND REPRESENTS THE SYSTEM-GENERATED IMAGE OF PETER'S POSITION.

77 FR 3108 - Dividend Equivalents From Sources Within the United States

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-23

.... Erwin or D. Peter Merkel at (202) 622-3870 (not a toll-free number). SUPPLEMENTARY INFORMATION... is D. Peter Merkel, the Office of Associate Chief Counsel (International). Other personnel from the...

77 FR 53141 - Dividend Equivalents From Sources Within the United States

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-31

.... Peter Merkel at (202) 622-3870 (not a toll-free number). SUPPLEMENTARY INFORMATION: Background On... Information The principal author of these regulations is D. Peter Merkel, the Office of Associate Chief...

78 FR 25309 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... Bing, at (202) 314-6403 or by email at [email protected] . FOR MEDIA INFORMATION CONTACT: Peter Knudson, at (202) 314-6100 or by email at peter[email protected] for the Safety Report--Reaching Zero: Actions...

78 FR 11660 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... Boulevard, Rockville, MD 20852 (Telephone Conference Call). Contact Person: Peter Zelazowski, Ph.D..., peter[email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.864, Population...

Urinary catheters - what to ask your doctor

MedlinePlus

... incontinence. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ... incontinence. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, ...

[Award of the Salomon-Neumann-Medal 2017 - Speech of the Laureate Prof. Bernt-Peter Robra, 5 September 2017, St. Peter´s Church Lübeck].

PubMed

Robra, Bernt-Peter

2018-02-19

The Salomon-Neumann-Medal 2017 of the German Society for Social Medicine and Prevention (DGSMP) was awarded to Bernt-Peter Robra, Institute for Social Medicine and Health Economics (ISMG) of the Otto von Guericke University Magdeburg. The person and scientific merits of Manfred Pflanz are valued and topics of the masterplan2020-process are highlighted, that offer chances for developments in medicine and public health. © Georg Thieme Verlag KG Stuttgart · New York.

Minfong Ho: Politics in Prose

ERIC Educational Resources Information Center

Wiggins, Joy L.

2006-01-01

In this article, the author interviews Minfong Ho, an award-winning Thai writer of children's and young adult novels. Ho was born in Burma to Chinese parents in 1951, raised in Singapore and Thailand, educated in Bangkok, Taiwan, and at Cornell University in New York. Ho's first novel, "Sing to the Dawn," won first prize from the Council of…

K2Ho(PO4)(WO4)

PubMed Central

Terebilenko, Katherina V.; Zatovsky, Igor V.; Baumer, Vyacheslav N.; Slobodyanik, Nikolay S.; Shishkin, Oleg V.

2008-01-01

A new compound, dipotassium holmium(III) phosphate(V) tungstate(VI), K2Ho(PO4)(WO4), has been obtained during investigation of the K2O–P2O5–WO3–HoF3 phase system using the flux technique. The compound is isotypic with K2Bi(PO4)(WO4). Its framework structure consists of flat ∞ 2[HoPO4] layers parallel to (100) that are made up of ∞ 1[HoO8] zigzag chains inter­linked via slightly distorted PO4 tetra­hedra. WO4 tetra­hedra are attached above and below these layers, leaving space for the K+ counter-cations. The HoO8, PO4 and WO4 units exhibit 2 symmetry. PMID:21580811

Editorial independence at medical journals owned by professional associations: a survey of editors.

PubMed

Davis, Ronald M; Müllner, Marcus

2002-10-01

The purpose of this study was to assess the degree of editorial independence at a sample of medical journals and the relationship between the journals and their owners. We surveyed the editors of 33 medical journals owned by not-for-profit organizations ("associations"), including 10 journals represented on the International Committee of Medical Journal Editors (nine of which are general medical journals) and a random sample of 23 specialist journals with high impact factors that are indexed by the Institute for Scientific Information. The main outcome measures were the authority to hire, fire, and oversee the work of the editor; the editor's tenure and financial compensation; control of the journal's budget; publication of material about the association; and the editor's perceptions about editorial independence and pressure over editorial content. Of the 33 editors, 23 (70%) reported having complete editorial freedom, and the remainder reported a high level of freedom (a score of > or = 8, where 10 equals complete editorial freedom and 1 equals no editorial freedom). Nevertheless, a substantial minority of editors reported having received at least some pressure in recent years over editorial content from the association's leadership (42%), senior staff (30%), or rank-and-file members (39%). The association's board of directors has the authority to hire (48%) or fire (55%) the editor for about half of the journals, and the editor reports to the board for 10 journals (30%). Twenty-three editors (70%) are appointed for a specific term (median term = 5 years). Three-fifths of the journals have no control over their profit, and the majority of journals use the association's legal counsel and/or media relations staff. Stronger safeguards are needed to give editors protection against pressure over editorial content, including written guarantees of editorial freedom and governance structures that support those guarantees. Strong safeguards are also needed because editors may have less freedom than they believe (especially if they have not yet tested their freedom in an area of controversy).

Reflections on 35 years with Applied Optics: outgoing editorial.

PubMed

Mait, Joseph N

2014-10-20

Applied Optics' Editor-in-Chief, Joseph N. Mait reflects on his experience as a reader, author, reviewer and eventual editor of the journal. Dr. Mait also introduces the incoming Editor-in-Chief, Ronald G. Driggers and acknowledges outgoing Division Editor, T.-C. Poon.

Travels with the Fossil Hunters

NASA Astrophysics Data System (ADS)

Whybrow, Peter J.

2000-04-01

Whether dodging bullets in West Africa, or rabid dogs in Pakistan, surviving yak-butter tea in Tibet, or eating raw fish in China, the life of a globe-trotting fossil hunter is often hazardous and always filled with surprises. Travels with the Fossil Hunters lets readers share the wonder, joys of discovery, and excitement of these intrepid scientists. Packed with more than 100 beautiful, full-color photographs, the volume takes readers on twelve expeditions to remote parts of the world in search of diverse fossil remains, from those of dinosaurs to human ancestors. Each expedition by paleontologists from London's Natural History Museum reveals the problems and challenges of working in extreme conditions, from the deserts of the Sahara and Yemen to the frozen wastes of Antarctica, from the mountains of India to the forests of Latvia. Along the way they also describe the paleontology and geology of the countries they visit and the scientific reasons for their expeditions. With a foreword from Sir David Attenborough and an introduction from Richard Fortey, this fascinating book will appeal to amateur and professional fossil hunters alike and to readers interested in accounts of exotic locales. Peter Whybrow is a research scientist at the Natural History Museum, London. His research interests include Arabian Miocene vertebrates, paleoclimates, paleogeography, and biotic diversity. He is senior editor with A. Hill of Fossil Vertebrates of Arabia (Yale University Press, New Haven, 1999).

Science Matters Podcast: Questions and Answers with EPA's Dr. Peter Grevatt

EPA Pesticide Factsheets

Listen to a podcast with Dr. Peter Grevatt, the director of EPA's Office of Children's Health Protection, as he answers questions about children's health, or read some of the highlights from the conversation here.

78 FR 17419 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... Person: Peter Zelazowski, Ph.D., Scientific Review Officer, Division of Scientific Review, Eunice Kennedy..., Bethesda, MD 20892, 301-435-6902, peter[email protected] . (Catalogue of Federal Domestic Assistance...

77 FR 60447 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-03

..., 6100 Executive Boulevard, Rockville, MD 20852 (Telephone Conference Call). Contact Person: Peter..., 301-435-6902, peter[email protected] . (Catalogue of Federal Domestic Assistance Program Nos. 93.864...

Autonomy in R. S. Peters' Educational Theory

ERIC Educational Resources Information Center

Cuypers, Stefaan E.

2009-01-01

Autonomy is, among other things, an actual psychological condition, a capacity that can be developed, and an educational ideal. This paper contextualises, analyses, criticises and extends the theory of Richard S. Peters on these three aspects of autonomy.

75 FR 81644 - Hearing of The Judicial Conference Committee on Criminal Rules

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... San Francisco, CA FOR FURTHER INFORMATION CONTACT: Peter G. McCabe, Secretary, Rules Committee Support.... Dated: December 21, 2010. Peter G. McCabe, Rules Committee Support Office. [FR Doc. 2010-32415 Filed 12...

Anterior segment dysgenesis (Peters' anomaly) in two snow leopard (Panthera uncia) cubs.

PubMed

Hamoudi, Hassan; Rudnick, Jens-Christian; Prause, Jan U; Tauscher, Kerstin; Breithaupt, Angele; Teifke, Jens P; Heegaard, Steffen

2013-07-01

Two sibling snow leopards, a male and a female, with bilateral anterior segment dysgenesis (ASD), are reported. Both snow leopards also had colobomas of both upper eyelids. All eyes exhibited a central corneal opacity associated with a defect in posterior corneal stroma, endothelium and Descemet's membrane. Iris strands were present attached to the termination of Descemet's membrane and to the periphery of the posterior corneal defect. The iris was hypoplastic, and cataract was present in all four eyes. The left eye of the female was microphthalmic, with no trabecular meshwork and with persistent remnant of the hyaloid artery. The male had hydrocephalus and thus some of the features of Peters' plus syndrome (Peters' anomaly in addition to systemic malformations). The histological findings in the eyes of these snow leopard siblings are identical with those described in humans with Peters' anomaly. © 2012 American College of Veterinary Ophthalmologists.

New Editors Appointed for Water Resources Research

NASA Astrophysics Data System (ADS)

2009-03-01

Praveen Kumar (University of Illinois at Urbana-Champaign), the newly appointed editor in chief of Water Resources Research (WRR), heads the new team of editors for the journal. The other editors are Tom Torgersen (University of Connecticut, Groton), who continues his editorship; Tissa Illangasekare (Colorado School of Mines, Golden); Graham Sander (Loughborough University, Loughborough, UK); and John Selker (Oregon State University, Corvallis). Hoshin Gupta (University of Arizona, Tucson) will join WRR at the end of 2009. The new editors will begin receiving submissions immediately. The incoming editorial board thanks outgoing editors Marc Parlange, Brian Berkowitz, Amilcare Porporato, and Scott Tyler, all of whom will assist during the transition.

Exploring the Relationship Between Octane Sensitivity and Heat-of-Vaporization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sluder, C. Scott; Szybist, James P.; McCormick, Robert L.

2016-04-05

The latent heat-of-vaporization (HoV) of blends of biofuel and hydrocarbon components into gasolines has recently experienced expanded interest because of the potential for increased HoV to increase fuel knock resistance in direct-injection (DI) engines. Several studies have been conducted, with some studies identifying an additional anti-knock benefit from HoV and others failing to arrive at the same conclusion. Consideration of these studies holistically shows that they can be grouped according to the level of fuel octane sensitivity variation within their fuel matrices. When comparing fuels of different octane sensitivity significant additional anti-knock benefits associated with HoV are sometimes observed. Studiesmore » that fix the octane sensitivity find that HoV does not produce additional anti-knock benefit. New studies were performed at ORNL and NREL to further investigate the relationship between HoV and octane sensitivity. Three fuels were formulated for the ORNL study with matched RON and octane sensitivity, but with differing HoV. Experiments with these fuels in a 1.6-liter GTDI engine showed that the fuels exhibited very similar combustion phasing under knock-limited spark advance (KLSA) conditions. Fuels having a range of RON, octane sensitivity, and HoV were tested at NREL in a single-cylinder GDI engine under conditions where octane sensitivity has little effect on knock resistance. KLSA was found to be well correlated with RON. These results reinforce the concept that HoV anti-knock effects can be viewed as a contributor to octane sensitivity. From this viewpoint, HoV effects manifest themselves as increases in octane sensitivity.« less

Enhancement of red upconversion emission of cubic phase NaLuF{sub 4}: Yb{sup 3+}/Ho{sup 3+}/Ce{sup 3+} nanocrystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Wei, E-mail: gaowei@xupt.edu.com; Dong, Jun, E-mail: dongjun@xupt.edu.cn; Liu, Jihong

Highlights: • The upconversion emission of Ho{sup 3+} ions was tuned from green to red. • The upconversion mechanism of Ho{sup 3+} ions was discussed based on emission spectrum. • The conversion efficiency between Ho{sup 3+} and Ce{sup 3+} were studied and calculated. - Abstract: The red upconversion emission of lanthanide-doped fluoride nanocrystals have great potential applications in color display and anticounterfeiting applications, especially for biological imaging and biomedical. In this work, a significant enhancement of red upconversion emission of Ho{sup 3+} ions was successfully obtained in the cubic phase NaLuF{sub 4} nanocrystals through codoping Ce{sup 3+} ions under NIRmore » 980 nm excitation. The ratio of red-to-green emission of Ho{sup 3+} ions was enhanced about 10-fold, which is due to two efficient cross relaxation processes derived from Ho{sup 3+} and Ce{sup 3+} ions promoted the red emission and quenched the green emission. The upconversion emission and luminescent colors of NaLuF{sub 4}: Yb{sup 3+}/Ho{sup 3+} nanocrystals were carefully investigated by a confocal microscopy setup. The possible upconversion emission mechanism and conversion efficiency of cross relaxation between Ho{sup 3+} and Ce{sup 3+} ions were discussed in detail. The current study suggests that strong red emission of NaLuF{sub 4}: Yb{sup 3+}/Ho{sup 3+}/Ce{sup 3+} nanomaterials can be used for color display and anticounterfeiting techniques.« less

Influence of transcutaneous electrical stimulation on heterotopic ossification: an experimental study in Wistar rats

PubMed Central

Zotz, T.G.G.; de Paula, J.B.

2015-01-01

Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues, resulting in joint mobility deficit and pain. Different treatment modalities have been tried to prevent HO development, but there is no consensus on a therapeutic approach. Since electrical stimulation is a widely used resource in physiotherapy practice to stimulate joint mobility, with analgesic and anti-inflammatory effects, its usefulness for HO treatment was investigated. We aimed to identify the influence of electrical stimulation on induced HO in Wistar rats. Thirty-six male rats (350-390 g) were used, and all animals were anesthetized for blood sampling before HO induction, to quantify the serum alkaline phosphatase. HO induction was performed by bone marrow implantation in both quadriceps of the animals, which were then divided into 3 groups: control (CG), transcutaneous electrical nerve stimulation (TENS) group (TG), and functional electrical stimulation (FES) group (FG) with 12 rats each. All animals were anesthetized and electrically stimulated twice per week, for 35 days from induction day. After this period, another blood sample was collected and quadriceps muscles were bilaterally removed for histological and calcium analysis and the rats were killed. Calcium levels in muscles showed significantly lower results when comparing TG and FG (P<0.001) and between TG and CG (P<0.001). Qualitative histological analyses confirmed 100% HO in FG and CG, while in TG the HO was detected in 54.5% of the animals. The effects of the muscle contractions caused by FES increased HO, while anti-inflammatory effects of TENS reduced HO. PMID:26292223

Methamphetamine induces heme oxygenase-1 expression in cortical neurons and glia to prevent its toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y.-N.; Wu, C.-H.; Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan 114

2009-11-01

The impairment of cognitive and motor functions in humans and animals caused by methamphetamine (METH) administration underscores the importance of METH toxicity in cortical neurons. The heme oxygenase-1 (HO-1) exerts a cytoprotective effect against various neuronal injures; however, it remains unclear whether HO-1 is involved in METH-induced toxicity. We used primary cortical neuron/glia cocultures to explore the role of HO-1 in METH-induced toxicity. Exposure of cultured cells to various concentrations of METH (0.1, 0.5, 1, 3, 5, and 10 mM) led to cytotoxicity in a concentration-dependent manner. A METH concentration of 5 mM, which caused 50% of neuronal death andmore » glial activation, was chosen for subsequent experiments. RT-PCR and Western blot analysis revealed that METH significantly induced HO-1 mRNA and protein expression, both preceded cell death. Double and triple immunofluorescence staining further identified HO-1-positive cells as activated astrocytes, microglia, and viable neurons, but not dying neurons. Inhibition of the p38 mitogen-activated protein kinase pathway significantly blocked HO-1 induction by METH and aggravated METH neurotoxicity. Inhibition of HO activity using tin protoporphyrine IX significantly reduced HO activity and exacerbated METH neurotoxicity. However, prior induction of HO-1 using cobalt protoporphyrine IX partially protected neurons from METH toxicity. Taken together, our results suggest that induction of HO-1 by METH via the p38 signaling pathway may be protective, albeit insufficient to completely protect cortical neurons from METH toxicity.« less

Low temperature X-ray structure analyses combined with NBO studies of a new heteroleptic octa-coordinated Holmium(III) complex with N,N,N-tridentate hydrazono-phthalazine-type ligand

NASA Astrophysics Data System (ADS)

Soliman, Saied M.; El-Faham, Ayman

2018-04-01

The new heteroleptic [HoL(H2O)5]Br3 complex, L is hydrazono-phthalazine ligand, is synthesized and its molecular structure aspects were analyzed using single crystal X-ray structure (SCXRD), Hirshfeld (HF) analysis, quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) method. The SCXRD showed that the Ho is octa-coordinated with one N,N,N-tridentate ligand L and five water molecules. The HF analysis is used to analyze the molecular packing in the [HoL(H2O)5]Br3crystal structure. The complex cations are connected via strong Osbnd H⋯Br and Nsbnd H⋯Br H-bonding interactions which have greater importance than the Csbnd H⋯Br contacts. Also, all the Hosbnd N and Hosbnd O bonds have the characteristics of closed shell interactions using QTAIM. The natural orbitals included in these interactions were analyzed using NBO method. The alpha LP*(8)Ho and beta LP*(4)Ho which have mainly s-orbital characters are the most important anti-bonding natural orbitals included in all Ho-N and Hosbnd O bonds. The rest of the Ho anti-bonding orbitals which have either p or d-orbital characters shared partially in the Ho-ligands interactions. Natural charges analysis revealed the presence of significant amount of electron density (0.9225-0.9300 e) transferred from the ligands to Ho (2.0700-2.0775 e). Spherical spin density with ∼4.0 e is predicted over the Ho atom.

Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

NASA Astrophysics Data System (ADS)

Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

1995-07-01

Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

Cerebroprotective functions of HO-2.

PubMed

Parfenova, Helena; Leffler, Charles W

2008-01-01

The constitutive isoform of heme oxygenase, HO-2, is highly expressed in the brain and in cerebral vessels. HO-2 functions in the brain have been evaluated using pharmacological inhibitors of the enzyme and HO-2 gene deletion in in vivo animal models and in cultured cells (neurons, astrocytes, cerebral vascular endothelial cells). Rapid activation of HO-2 via post-translational modifications without upregulation of HO-2 expression or HO-1 induction coincides with the increase in cerebral blood flow aimed at maintaining brain homeostasis and neuronal survival during seizures, hypoxia, and hypotension. Pharmacological inhibition or gene deletion of brain HO-2 exacerbates oxidative stress induced by seizures, glutamate, and inflammatory cytokines, and causes cerebral vascular injury. Carbon monoxide (CO) and bilirubin, the end products of HO-catalyzed heme degradation, have distinct cytoprotective functions. CO, by binding to a heme prosthetic group, regulates the key components of cell signaling, including BK(Ca) channels, guanylyl cyclase, NADPH oxidase, and the mitochondria respiratory chain. Cerebral vasodilator effects of CO are mediated via activation of BK(Ca) channels and guanylyl cyclase. CO, by inhibiting the major components of endogenous oxidant-generating machinery, NADPH oxidase and the cytochrome C oxidase of the mitochondrial respiratory chain, blocks formation of reactive oxygen species. Bilirubin, via redox cycling with biliverdin, is a potent oxidant scavenger that removes preformed oxidants. Overall, HO-2 has dual housekeeping cerebroprotective functions by maintaining autoregulation of cerebral blood flow aimed at improving neuronal survival in a changing environment, and by providing an effective defense mechanism that blocks oxidant formation and prevents cell death caused by oxidative stress.

Development of two measures of client engagement for use in home aged care.

PubMed

Baker, Jess Rose; Harrison, Fleur; Low, Lee-Fay

2016-05-01

The aim of the study was to develop and validate measures of client engagement in aged homecare. The Homecare Measure of Engagement-Staff questionnaire (HoME-S) is a self-complete measure of six dimensions of client engagement: client acceptance, attention, attitude, appropriateness, engagement duration and passivity. The Homecare Measure of Engagement-Client/Family report (HoME-CF) is a researcher-rated interview which obtains client and/or family perspectives regarding frequency and valence of conversational and recreational engagement during care worker visits. Care workers (n = 84) completed the HoME-S and a measure of relationship bond with client. Researchers interviewed clients (n = 164) and/or their family (n = 117) and completed the HoME-CF, and measures of agitation, dysphoria, apathy and cognitive functioning. The HoME-S and HoME-CF demonstrated good test-retest and inter-rater reliability, and showed significant negative correlations with apathy, agitation and non-English-speaking background. Controlling for client and care service characteristics, a stronger care worker-client relationship bond and English-speaking background were independently associated with higher HoME-S scores, and apathy was independently associated with higher HoME-CF scores. In conclusion, the HoME-S and HoME-CF are psychometrically sound engagement measures for use in homecare. Clients who are apathetic or from non-English-speaking backgrounds may be less responsive to traditional care worker engagement strategies. Engagement may be augmented in clients who have stronger relationships with their care workers. © 2015 John Wiley & Sons Ltd.

Butylated Hydroxyanisole Stimulates Heme Oxygenase-1 Gene Expression and Inhibits Neointima Formation in Rat Arteries

PubMed Central

Liu, Xiao-ming; Azam, Mohammed A.; Peyton, Kelly J.; Ensenat, Diana; Keswani, Amit N.; Wang, Hong; Durante, William

2007-01-01

Objective Butylated hydroxyanisole (BHA) is a synthetic phenolic compound that is a potent inducer of phase II genes. Since heme oxygenase-1 (HO-1) is a vasoprotective protein that is upregulated by phase II inducers, the present study examined the effects of BHA on HO-1 gene expression and vascular smooth muscle cell proliferation. Methods The regulation of HO-1 gene expression and vascular cell growth by BHA was studied in cultured rat aortic smooth muscle cells and in balloon injured rat carotid arteries. Results Treatment of cultured smooth muscle cells with BHA stimulated the expression of HO-1 protein, mRNA and promoter activity in a time- and concentration-dependent manner. BHA-mediated HO-1 expression was dependent on the activation of NF-E2-related factor-2 by p38 mitogen-activated protein kinase. BHA also inhibited cell cycle progression and DNA synthesis in a HO-1-dependent manner. In addition, the local perivascular delivery of BHA immediately after arterial injury of rat carotid arteries induced HO-1 protein expression and markedly attenuated neointima formation. Conclusions These studies demonstrate that BHA stimulates HO-1 gene expression in vascular smooth muscle cells, and that the induction of HO-1 contributes to the antiproliferative actions of this phenolic antioxidant. BHA represents a potentially novel therapeutic agent in treating or preventing vasculoproliferative disease. PMID:17320844

Sensitizing effect of Ho3+ on the Er3+: 2.7 μm-emission in fluoride glass

NASA Astrophysics Data System (ADS)

Huang, Feifei; Li, Xia; Liu, Xueqiang; Zhang, Junjie; Hu, Lili; Chen, Danping

2014-03-01

The fluorescence properties of 2.7 μm emission and energy transfer mechanism of Ho3+/Er3+ co-doped fluoride glass (ZBYA) have been investigated in the present paper. Ho3+ strengthens the Er3+: 2.7 μm emission in the ZBYA glasses due to the energy transfer from Er3+ to Ho3+, while the 1.5 μm emission decreases dramatically. The optimized concentration ratio of Er3+ to Ho3+ is found to be 1:1 in our glass system. The absorption and emission spectra are tested and the sample possesses large emission cross section (16.5 × 10-21 cm2) around 2.7 μm along with larger radiative transition probability (25.11 S-1) on the basis of Judd-Ofelt and Fuchtbauer-Ladenburg theories. Additionally, the energy transfer microparameters are calculated using Förster-Dexter theory and the result shows the energy transfer coefficient of Er3+:4I13/2 → Ho3+:5I7 is 24 times larger than that of Er3+:4I11/2 → Ho3+:5I6. Our results show that Er3+: 2.7 μm emission can be sensitized by Ho3+ efficiently, and this Er3+/Ho3+-codoped fluoride glasses might have potential application in mid-infrared lasers.

Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells.

PubMed

Abraham, Nader G; Quan, Shuo; Mieyal, Paul A; Yang, Liming; Burke-Wolin, Theresa; Mingone, Christopher J; Goodman, Alvin I; Nasjletti, Alberto; Wolin, Michael S

2002-11-01

Carbon monoxide (CO) stimulates guanylate cyclase (GC) and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels. We transfected rat-lung pulmonary endothelial cells with a retrovirus-mediated human heme oxygenase (hHO)-1 gene. Pulmonary cells that expressed hHO-1 exhibited a fourfold increase in HO activity associated with decreases in the steady-state levels of heme and cGMP without changes in soluble GC (sGC) and endothelial nitric oxide synthase (NOS) proteins or basal nitrite production. Heme elicited significant increases in CO production and intracellular cGMP levels in both pulmonary endothelial and pulmonary hHO-1-expressing cells. N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly decreased cGMP levels in heme-treated pulmonary endothelial cells but not heme-treated hHO-1-expressing cells. In the presence of exogenous heme, CO and cGMP levels in hHO-1-expressing cells exceeded the corresponding levels in pulmonary endothelial cells. Acute exposure of endothelial cells to SnCl2, which is an inducer of HO-1, increased cGMP levels, whereas chronic exposure decreased heme and cGMP levels. These results indicate that prolonged overexpression of HO-1 ultimately decreases sGC activity by limiting the availability of cellular heme. Heme activates sGC and enhances cGMP levels via a mechanism that is largely insensitive to NOS inhibition.

Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance.

PubMed

Zeng, Bin; Chen, Honglei; Zhu, Chengang; Ren, Xiaofeng; Lin, Guosheng; Cao, Feng

2008-10-01

Bone marrow mesenchymal stem cells (MSCs) have the potential to repair the infarcted myocardium and improve cardiac function. However, this approach is limited by its poor viability after transplantation, and controversy still exists over the mechanism by which MSCs contribute to the tissue repair. The human heme oxygenase-1 (hHO-1) was transfected into cultured MSCs using an adenoviral vector. 1 x 10(6) Ad-hHO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS only (PBS group) were injected intramyocardially into rat hearts 1h after myocardial infarction. HO-1-MSCs survived in the infarcted myocardium, and expressed hHO-1 mRNA. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) was significantly enhanced in HO-1-MSCs-treated hearts. At the same time, there were significant reduction of TNF-alpha, IL-1-beta and IL-6 mRNA, and marked increase of IL-10 mRNA in HO-1-MSCs-treated hearts. Moreover, a further downregulation of proapoptotic protein, Bax, and a marked increase in microvessel density were observed in HO-1-MSCs-treated hearts. The infarct size and cardiac performance were also significantly improved in HO-1-MSCs-treated hearts. The combined approach improves MSCs survival and is superior to MSCs injection alone.

Interventions for the treatment of craniopharyngioma-related hypothalamic obesity: a systematic review.

PubMed

Ni, Weimin; Shi, Xiang'en

2018-06-23

Craniopharyngiomas (CPs) and their treatment are associated with hypothalamic damage that causes hypothalamic obesity (HO) in 30-70% of cases. Thus, there is ongoing research regarding tangible solutions for HO, as these patients have unrelenting resistance to basic weight-loss interventions. This review aims to summarize the interventions that are currently used to treat CP-related HO (CP-HO), including pharmacotherapy and bariatric surgery. The Cochrane Library, EMBASE, and PubMed databases were searched up to June 2017 for relevant reports. Two reviewers conducted independent evaluations of the identified studies. Eighteen publications were included in the systematic review, with three reports describing pharmacotherapy in randomized controlled trials and 15 reports describing bariatric surgery. Although several studies described effective interventions for treating CP-HO, the evidence base was limited by its low quality and our inability to perform a meta-analysis, which was related to a lack of adequate or integrated data. Octreotide appears to be a preferred treatment for CP-HO patients, based on currently limited data. Gastric bypass surgery may also be suitable for select CP-HO patients, based on a review of various procedures in this setting. Microsurgical preservation of the hypothalamic structures is mandatory to decrease CP-HO-related morbidity and mortality. Further studies with adequate analytical power and sufficient follow-up are needed to identify effective strategies for CP-HO treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Evidence-based outcomes of holmium laser enucleation of the prostate.

PubMed

Large, Tim; Krambeck, Amy E

2018-05-01

Holmium laser enucleation of the prostate (HoLEP) has been a mainstay therapy for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostate hyperplasia (BPH) for nearly 20 years. We briefly review current and sentinel publications that provide outcomes data after HoLEP. Current literature continues to support HoLEP as a versatile and durable surgical option for men with LUTS secondary to BPH. Despite evidence supporting durable symptom relief beyond 10 years even in large prostate glands, HoLEP is still not widely available to all patients. Concerns surrounding the learning curve of the procedure, high rates of retrograde ejaculation, and transient urinary incontinence seem to persist and limit the adoption of HoLEP by established urologists and residency training programs. Recent publications continue to show excellent short-term and long-term outcomes after HoLEP, in the categories of voiding function and patient satisfaction. Continued attempts to demonstrate equivalent outcomes of alternate-BPH surgical techniques are being met with renewed efforts by those performing HoLEP to demonstrate equivalent outcomes and patient safety during the learning phase of HoLEP for both mentored and self-directed surgical training.

Beneficial effects of the heme oxygenase-1/carbon monoxide system in patients with severe sepsis/septic shock.

PubMed

Takaki, Shoji; Takeyama, Naoshi; Kajita, Yuka; Yabuki, Teru; Noguchi, Hiroki; Miki, Yasuo; Inoue, Yasusuke; Nakagawa, Takashi; Noguchi, Hiroshi

2010-01-01

We evaluated the relations among the arterial carbon monoxide (CO) concentration, heme oxygenase (HO)-1 expression by monocytes, oxidative stress, plasma levels of cytokines and bilirubin, and the outcome of patients with severe sepsis or septic shock. Thirty-six patients who fulfilled the criteria for severe sepsis or septic shock and 21 other patients without sepsis during their stay in the intensive care unit were studied. HO-1 protein expression by monocytes, arterial CO, oxidative stress, bilirubin, and cytokines were measured. Arterial blood CO, cytokine, and bilirubin levels, and monocyte HO-1 protein expression were higher in patients with severe sepsis/septic shock than in non-septic patients. Increased HO-1 expression was related to the arterial CO concentration and oxidative stress. There was a positive correlation between survival and increased HO-1 protein expression or a higher CO level. Arterial CO and monocyte HO-1 protein expression were increased in critically ill patients, particularly those with severe sepsis or septic shock, suggesting that oxidative stress is closely related to HO-1 expression. The HO-1/CO system may play an important role in sepsis.

Direct Mouse Trauma/Burn Model of Heterotopic Ossification

PubMed Central

Peterson, Jonathan R.; Agarwal, Shailesh; Brownley, R. Cameron; Loder, Shawn J.; Ranganathan, Kavitha; Cederna, Paul S.; Mishina, Yuji; Wang, Stewart C.; Levi, Benjamin

2015-01-01

Heterotopic ossification (HO) is the formation of bone outside of the skeleton which forms following major trauma, burn injuries, and orthopaedic surgical procedures. The majority of animal models used to study HO rely on the application of exogenous substances, such as bone morphogenetic protein (BMP), exogenous cell constructs, or genetic mutations in BMP signaling. While these models are useful they do not accurately reproduce the inflammatory states that cause the majority of cases of HO. Here we describe a burn/tenotomy model in mice that reliably produces focused HO. This protocol involves creating a 30% total body surface area partial thickness contact burn on the dorsal skin as well as division of the Achilles tendon at its midpoint. Relying solely on traumatic injury to induce HO at a predictable location allows for time-course study of endochondral heterotopic bone formation from intrinsic physiologic processes and environment only. This method could prove instrumental in understanding the inflammatory and osteogenic pathways involved in trauma-induced HO. Furthermore, because HO develops in a predictable location and time-course in this model, it allows for research to improve early imaging strategies and treatment modalities to prevent HO formation. PMID:26274052

Adiponectin-Mediated Heme Oxygenase-1 Induction Protects Against Iron-Induced Liver Injury via a PPARα-Dependent Mechanism

PubMed Central

Lin, Heng; Yu, Chun-Hsien; Jen, Chih-Yu; Cheng, Ching-Feng; Chou, Ying; Chang, Chih-Cheng; Juan, Shu-Hui

2010-01-01

Protective effects of adiponectin (APN; an adipocytokine) were shown against various oxidative challenges; however, its therapeutic implications and the mechanisms underlying hepatic iron overload remain unclear. Herein, we show that the deleterious effects of iron dextran on liver function and iron deposition were significantly reversed by adiponectin gene therapy, which was accompanied by AMP-activated protein kinase (AMPK) phosphorylation and heme oxygenase (HO)-1 induction. Furthermore, AMPK-mediated peroxisome proliferator-activated receptor-α (PPARα) activation by APN was ascribable to HO-1 induction. Additionally, we revealed direct transcriptional regulation of HO-1 by the binding of PPARα to a PPAR-responsive element (PPRE) by various experimental assessments. Interestingly, overexpression of HO-1 in hepatocytes mimicked the protective effect of APN in attenuating iron-mediated injury, whereas it was abolished by SnPP and small interfering HO-1. Furthermore, bilirubin, the end-product of the HO-1 reaction, but not CO, protected hepatocytes from iron dextran-mediated caspase activation. Herein, we demonstrate a novel functional PPRE in the promoter regions of HO-1, and APN-mediated HO-1 induction elicited an antiapoptotic effect and a decrease in iron deposition in hepatocytes subjected to iron challenge. PMID:20709802

Carbon monoxide derived from heme oxygenase-2 mediates reduction of methylmercury toxicity in SH-SY5Y cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toyama, Takashi; Research Fellow of the Japan Society for the Promotion of Science; Shinkai, Yasuhiro

2010-11-15

We examined the contribution of carbon monoxide (CO), an enzymatic product of heme oxygenase (HO), to methylmercury (MeHg) cytotoxicity in SH-SY5Y cells, because this gas molecule is reported to activate Nrf2, which plays a protective role against MeHg-mediated cell damage. Exposure of SH-SY5Y cells to CO gas resulted in protection against MeHg cytotoxicity, with activation of Nrf2. Interestingly, pretreatment with tin-protoporphyrin IX, a specific inhibitor of HO, caused a reduction in basal Nrf2 activity and thus enhanced sensitivity to MeHg. No induction of isoform 1 of HO (HO-1) was seen during MeHg exposure, but constitutive expression of isoform 2 (HO-2)more » occurred, suggesting that CO produced by HO-2 is the main participant in the protection against MeHg toxicity. Studies of small interfering RNA-mediated knockdown of HO-2 in the cells supported this possibility. Our results suggest that CO gas and its producing enzyme HO-2 are key molecules in cellular protection against MeHg, presumably through basal activation of Nrf2.« less

Cysteine-independent activation/inhibition of heme oxygenase-2

PubMed Central

Vukomanovic, Dragic; Rahman, Mona N.; Maines, Mahin D.; Ozolinš, Terence RS; Szarek, Walter A.; Jia, Zongchao; Nakatsu, Kanji

2016-01-01

Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282. PMID:27826418

Cysteine-independent activation/inhibition of heme oxygenase-2.

PubMed

Vukomanovic, Dragic; Rahman, Mona N; Maines, Mahin D; Ozolinš, Terence Rs; Szarek, Walter A; Jia, Zongchao; Nakatsu, Kanji

2016-03-01

Reactive thiols of cysteine (cys) residues in proteins play a key role in transforming chemical reactivity into a biological response. The heme oxygenase-2 (HO-2) isozyme contains two cys residues that have been implicated in binding of heme and also the regulation of its activity. In this paper, we address the question of a role for cys residues for the HO-2 inhibitors or activators designed in our laboratory. We tested the activity of full length recombinant human heme oxygenase-2 (FL-hHO-2) and its analog in which cys265 and cys282 were both replaced by alanine to determine the effect on activation by menadione (MD) and inhibition by QC-2350. Similar inhibition by QC-2350 and almost identical activation by MD was observed for both recombinant FL-hHO-2s. Our findings are interpreted to mean that thiols of FL-hHO-2s are not involved in HO-2 activation or inhibition by the compounds that have been designed and identified by us. Activation or inhibition of HO-2 by our compounds should be attributed to a mechanism other than altering binding affinity of HO-2 for heme through cys265 and cys282.

The effect of curcumin on insulin release in rat-isolated pancreatic islets.

PubMed

Abdel Aziz, Mohamed T; El-Asmar, Mohamed F; El Nadi, Essam G; Wassef, Mohamed A; Ahmed, Hanan H; Rashed, Laila A; Obaia, Eman M; Sabry, Dina; Hassouna, Amira A; Abdel Aziz, Ahmed T

2010-08-01

Curcumin exerts a hypoglycemic action and induces heme-oxygenase-1 (HO-1). We evaluated the effect of curcumin on isolated islets of Langerhans and studied whether its action on insulin secretion is mediated by inducible HO-1. Islets were isolated from rats and divided into control islets, islets incubated in different curcumin concentrations, islets incubated in hemin, islets incubated in curcumin and HO inhibitor, stannous mesoporphyrin (SnMP), islets incubated in hemin and SnMP, islets incubated in SnMP only, and islets incubated in 16.7 mmol/L glucose. Heme-oxygenase activity, HO-1 expression, and insulin estimation was assessed. Insulin secretion, HO-1 gene expression and HO activity were significantly increased in islets incubated in curcumin, hemin, and glucose compared with controls. This increase in insulin secretion was significantly decreased by incubation of islets in SnMP. The action of curcumin on insulin secretion from the isolated islets may be, in part, mediated through increased HO-1 gene expression.

Crystal Growth and Scintillation Properties of Ho-Doped Lu3Al5O12 Single Crystals

NASA Astrophysics Data System (ADS)

Sugiyama, Makoto; Yanagida, Takayuki; Fujimoto, Yutaka; Totsuka, Daisuke; Yokota, Yuui; Kurosawa, Shunsuke; Futami, Yoshisuke; Yoshikawa, Akira

2012-10-01

The crystals of 0.1, 0.5, 1, and 3% Ho doped Lu3Al5O12 (Ho:LuAG) grown by the micro-pulling-down method were examined for their scintillation properties. At wavelengths longer than 300 nm, Ho:LuAG crystals demonstrated around 60% transparency with many absorption peaks attributed to Ho3+ 4f10-4 f10 transitions. When excited by 241Am α-ray to obtain radio luminescence spectra, broad host emission and four sharp Ho3+ 4f10-4 f10 emission peaks were detected in the visible region. Light yields and decay time profiles of the samples irradiated by 137Cs γ-ray were measured using photomultiplier tubes R7600 (Hamamatsu). Ho 0.5%:LuAG showed the highest light yield of 3100 ±310 photons/MeV among the present samples. The decay time profiles were well reproduced by two components exponential approximation consisting of 0.5-1 μs and 3-6 μs.

Predicting lanthanide cluster properties: a comparison with the observed optical spectra of HO 2

NASA Astrophysics Data System (ADS)

Nemukhin, A. V.; Ermilov, A. Yu.; Petrukhina, M. A.; Klotzbücher, W. E.; Smets, J.

1997-10-01

Ab initio pseudopotential calculations for HO and HO 2 have been carried out in order to support an assignment of the bands observed in UV-visible spectra of matrix isolated holmium species. SCF, MCSCF and configuration interaction (CI) procedures have been used with quasirelativistic pseudopotentials to compute the ground and excited state energies of HO and HO 2, together with the dipole transition moments. For HO 2, using a Q = 11 pseudopotential (describing the holmium atom in the 4f 106s 25d 1 electronic state), two transitions from the ground state σg2σu2πu2 to the states with principal excitations σu → πg and π u → σ g∗ are predicted at 499 and 524 nm. These two lines, with predicted close intensities, correlate nicely with the observed features at 498/504 and 558/563nm in the spectrum of matrix-isolated HO 2.

TRACE-P OH and HO2 Measurements with the Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS) on the DC-8

NASA Technical Reports Server (NTRS)

Brune, William H.; Martinez-Harder, Monica; Harder, Hartwig

2004-01-01

The Airborne Tropospheric Hydrogen Oxides Sensor (ATHOS) measures OH and HO2 from the NASA DC-8. This instrument detects OH by laser induced fluorescence (LIF) in detection chambers at low pressure and detects HO2 by chemical conversion with NO followed by LIF detection. The demonstrated detection limit (S/N=2, 5 min.) for OH is about 0.005 pptv (1x10(exp 6)/cu cm at 2 km altitude) and for HO2 is 0.05 pptv (1x10(exp 6)/cu cm at 2 km altitude). We will use ATHOS to measure OH, HO2, and HO2/OH during TRACE- P, analyze these results by comparing them against fundamental relationships and computer models, and publish the analyses. TRACE-P HO(x), measurements will help develop a clearer picture of the atmospheric oxidation and 0 3 production that occur as Asian pollution spreads across the Pacific Ocean.

Idiopathic inflammatory myopathies in adults: A comparative study of Bohan and Peter and European Neuromuscular Center 2004 criteria.

PubMed

Challa, Sundaram; Jakati, Saumya; Uppin, Megha S; Kannan, Meena A; Liza, Rajasekhar; Murthy Jagarlapudi, M K

2018-01-01

Bohan and Peter criteria are widely used for the diagnosis of idiopathic inflammatory myopathies (IIMs). Recently, European Neuromuscular Center (ENMC) formulated criteria to identify subgroups of IIMs. To compare the two diagnostic criteria in adult IIMs. This was a retrospective review of case records of histologically confirmed IIMs in adults between January 2014 and May 2015. Both the Bohan and Peter, and ENMC 2004 criteria were applied in the same group of patients to subgroup the IIMs. Muscle biopsy was evaluated in all the four domains: muscle fiber, inflammatory, connective tissue, and vascular, with the basic panel of histological stains. Sporadic inclusion body myositis (s-IBM) was diagnosed using ENMC IBM diagnostic research criteria 2011. During the study period, 69 patients fulfilled the ENMC criteria for IIMs including 16 patients with s-IBM. The subgrouping as per the ENMC criteria (53) was: dermatomyositis (DM) in 30; polymyositis (PM) in 2; immune-mediated necrotizing myopathy (IMNM) in 9; and nonspecific myositis (NM) in 12 patients, whereas subgrouping by the Bohan and Peter criteria was DM in 9 and PM with and without connective tissue disease (CTD) in 26 patients only. There was underdiagnosis of DM, as perifascicular atrophy is not recognized as a diagnostic histological feature, and overdiagnosis of PM with and without CTD due to poor characterization of histological features in PM by the Bohan and Peter criteria. Systematic evaluation of muscle biopsy according to the ENMC criteria with basic panel of histochemical stains improved the diagnostic yield of IIM significantly when compared to the Bohan and Peter criteria.

Mid-infrared lasing from Ho(3+) in bulk InF(3) glass.

PubMed

Berrou, Antoine; Kieleck, Christelle; Eichhorn, Marc

2015-04-15

We report on an Ho³⁺:InF₃ glass laser pumped by a Cr³⁺:LiSAF laser emitting at 889 nm. Ho³⁺:InF₃ glass is a promising material for direct mid-infrared lasers around 4 μm. To evaluate the performances of this new material, we compared it to an Ho³⁺:BYF crystalline laser pumped by the same source. At 650 mJ pump energy, 7.2 mJ (46 mJ) was obtained with Ho³⁺:InF₃ (Ho³⁺:BYF), respectively. This is, to the best of our knowledge, the first reported laser activity in this type of glass.

75 FR 81644 - Meeting of the Judicial Conference Advisory Committee on Rules of Appellate Procedure

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2010-12-28

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75 FR 81644 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

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42 CFR 406.34 - Determination of months to be counted for premium increase: Reenrollment.

Code of Federal Regulations, 2010 CFR

2010-10-01

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Measurements of HO2 chemical kinetics with a new detection method

NASA Technical Reports Server (NTRS)

Lee, L. C.; Suto, M.

1986-01-01

Research for the period from December 1, 1985 to May 31, 1986 is discussed, i.e., the reaction rate constant of HO2+O3 has been measured with a discharge-flow-tube apparatus. The HO2 radical was detected by the OH(A-X) photofragment emission produced from photodissociative excitation of HO2 at 147 nm. In the meantime, the optical emissions produced by the vacuum ultraviolet excitation of chemical species in the flow tube were investigated and used to examine the possibility for their interference with the HO2 detection. The research results are summarized below.

pH modulation of currents that contribute to the medium and slow afterhyperpolarizations in rat CA1 pyramidal neurones

PubMed Central

Kelly, Tony; Church, John

2004-01-01

We examined the effects of changes in pHo and pHi on currents contributing to the medium and slow afterhyperpolarizations (mIAHP and sIAHP, respectively) in rat CA1 neurones. Reducing pHo from 7.4 to 6.7 inhibited mIAHP and sIAHP whereas increasing pHo to 7.7 augmented mIAHP and, to a greater extent, sIAHP. The ability of changes in pHo to modulate mIAHP reflected changes in the Ca2+-activated K+ current, IAHP, and a Co2+- and XE991-resistant component of mIAHP, but not the muscarine-sensitive current, IM. In the presence of 1 μm TTX and 5 mm TEA, low pHo-evoked reductions in sIAHP were associated with reductions in Ca2+-dependent depolarizing potentials; because neither effect was attenuated when internal H+ buffering power was raised by including 100 mm tricine in the patch pipette, the actions of reductions in pHo to inhibit sIAHP and, possibly, IAHP in large part appear to reflect a low pHo-dependent decrease in Ca2+ influx. In contrast, the effects of high pHo to augment mIAHP and sIAHP were associated with relatively small increases in Ca2+ potentials but were significantly attenuated by 100 mm internal tricine, indicating that a rise in pHi consequent upon the rise in pHo was largely responsible. The possibility that changes in pHi could act to modulate mIAHP and sIAHP, independently of changes in Ca2+ influx, was also suggested by experiments in which pHi was lowered at a constant pHo by the external application of propionate or by the withdrawal of HCO3− from the perfusing medium. Lowering pHi at a constant pHo had little effect on Ca2+ potentials but inhibited mIAHP and, to a greater extent, sIAHP, effects that were attenuated by 100 mm internal tricine. Together, the results indicate that changes in pHo and pHi modulate mIAHP and sIAHP in rat CA1 neurones and suggest that, depending on the direction of the pHo change, the sensitivities of the underlying currents to changes in Ca2+ influx and/or pHi may contribute to the effects of changes in pHo to modulate mIAHP and sIAHP. PMID:14608014

(⁹⁹m)Tc-MAA overestimates the absorbed dose to the lungs in radioembolization: a quantitative evaluation in patients treated with ¹⁶⁶Ho-microspheres.

PubMed

Elschot, Mattijs; Nijsen, Johannes F W; Lam, Marnix G E H; Smits, Maarten L J; Prince, Jip F; Viergever, Max A; van den Bosch, Maurice A A J; Zonnenberg, Bernard A; de Jong, Hugo W A M

2014-10-01

Radiation pneumonitis is a rare but serious complication of radioembolic therapy of liver tumours. Estimation of the mean absorbed dose to the lungs based on pretreatment diagnostic (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) imaging should prevent this, with administered activities adjusted accordingly. The accuracy of (99m)Tc-MAA-based lung absorbed dose estimates was evaluated and compared to absorbed dose estimates based on pretreatment diagnostic (166)Ho-microsphere imaging and to the actual lung absorbed doses after (166)Ho radioembolization. This prospective clinical study included 14 patients with chemorefractory, unresectable liver metastases treated with (166)Ho radioembolization. (99m)Tc-MAA-based and (166)Ho-microsphere-based estimation of lung absorbed doses was performed on pretreatment diagnostic planar scintigraphic and SPECT/CT images. The clinical analysis was preceded by an anthropomorphic torso phantom study with simulated lung shunt fractions of 0 to 30 % to determine the accuracy of the image-based lung absorbed dose estimates after (166)Ho radioembolization. In the phantom study, (166)Ho SPECT/CT-based lung absorbed dose estimates were more accurate (absolute error range 0.1 to -4.4 Gy) than (166)Ho planar scintigraphy-based lung absorbed dose estimates (absolute error range 9.5 to 12.1 Gy). Clinically, the actual median lung absorbed dose was 0.02 Gy (range 0.0 to 0.7 Gy) based on posttreatment (166)Ho-microsphere SPECT/CT imaging. Lung absorbed doses estimated on the basis of pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging (median 0.02 Gy, range 0.0 to 0.4 Gy) were significantly better predictors of the actual lung absorbed doses than doses estimated on the basis of (166)Ho-microsphere planar scintigraphy (median 10.4 Gy, range 4.0 to 17.3 Gy; p < 0.001), (99m)Tc-MAA SPECT/CT imaging (median 2.5 Gy, range 1.2 to 12.3 Gy; p < 0.001), and (99m)Tc-MAA planar scintigraphy (median 5.5 Gy, range 2.3 to 18.2 Gy; p < 0.001). In clinical practice, lung absorbed doses are significantly overestimated by pretreatment diagnostic (99m)Tc-MAA imaging. Pretreatment diagnostic (166)Ho-microsphere SPECT/CT imaging accurately predicts lung absorbed doses after (166)Ho radioembolization.

Gene transfer as a strategy to achieve permanent cardioprotection II: rAAV-mediated gene therapy with heme oxygenase-1 limits infarct size 1 year later without adverse functional consequences.

PubMed

Li, Qianhong; Guo, Yiru; Ou, Qinghui; Wu, Wen-Jian; Chen, Ning; Zhu, Xiaoping; Tan, Wei; Yuan, Fangping; Dawn, Buddhadeb; Luo, Li; Hunt, Gregory N; Bolli, Roberto

2011-11-01

Extensive evidence indicates that heme oxygenase-1 (HO-1) exerts potent cytoprotective effects in response to stress. Previous studies have shown that gene therapy with HO-1 protects against myocardial ischemia/reperfusion injury for up to 8 weeks after gene transfer. However, the long-term effects of HO-1 gene therapy on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the HO-1 gene (rAAV/HO-1) that enables long-lasting transgene expression. Mice received injections in the anterior LV wall of rAAV/LacZ (LacZ group) or rAAV/HO-1 (HO-1 group); 1 year later, they were subjected to a 30-min coronary occlusion (O) and 4 h of reperfusion (R). Cardiac HO-1 gene expression was confirmed at 1 month and 1 year after gene transfer by immunoblotting and immunohistochemistry analyses. In the HO-1 group, infarct size (% of risk region) was dramatically reduced at 1 year after gene transfer (11.2 ± 2.1%, n = 12, vs. 44.7 ± 3.6%, n = 8, in the LacZ group; P < 0.05). The infarct-sparing effects of HO-1 gene therapy at 1 year were as powerful as those observed 24 h after ischemic PC (six 4-min O/4-min R cycles) (15.0 ± 1.7%, n = 10). There were no appreciable changes in LV fractional shortening, LV ejection fraction, or LV end-diastolic or end-systolic diameter at 1 year after HO-1 gene transfer as compared to the age-matched controls or with the LacZ group. Histology showed no inflammation in the myocardium 1 year after rAAV/HO-1-mediated gene transfer. These results demonstrate, for the first time, that rAAV-mediated HO-1 gene transfer confers long-term (1 year), possibly permanent, cardioprotection without adverse functional consequences, providing proof of principle for the concept of achieving prophylactic cardioprotection (i.e., "immunization against infarction").

Kinetic and Thermodynamic Characterization of the Cobalt and Manganese Oxyhydroxide Cores Formed in Horse Spleen Ferritin

NASA Technical Reports Server (NTRS)

Zhang, Bo; Harb, John N.; Davis, Robert C.; Kim, Jae-Woo; Chu, Sang-Hyon; Choi, Sang; Miller, Tim; Watt, Gerald D.

2004-01-01

Horse spleen ferritin (HoSF) containing 800-1500 cobalt or 250-1200 manganese atoms as Co(O)OH and Mn(O)OH mineral cores within the HoSF interior (Co-HoSF and Mn-HoSF) was synthesized, and the chemical reactivity, kinetics of reduction, and the reduction potentials were measured. Microcoulometric and chemical reduction of HoSF containing the M(O)OH mineral core (M = Co or Mn) was rapid and quantitative with a reduction stoichiometry of 1.05+/-0.10 e/M forming a stable M(OH)2 mineral core. At pH 9.0, ascorbic acid (AH2), a two-electron reductant, effectively reduced the mineral cores; however, the reaction was incomplete and rapidly reached equilibrium. The addition of excess AH2 shifted the reaction to completion with a M(3+)/AH2 stoichiometry of 1.9-2.1, consistent with a single electron per metal atom reduction. The rate of reaction between M(0)OH and excess AH2 was measured by monitoring the decrease in mineral core absorbance with time. The reaction was first order in each reactant with second-order rate constants of 0.53 and 4.74/M/min, respectively, for Co- and Mn-HoSF at pH 9.0. From the variation of absorbance with increasing AH2 concentration, equilibrium constants at pH 9.0 of 5.0+/-1.9 for Co-HoSF and 2.9+/-0.9 for Mn-HoSF were calculated for 2M(O)OH + AH2 = 2M(OH)2 f D, where AH2 and D are ascorbic acid and dehydroascorbic acid, respectively. Consistent with these equilibrium constants, the standard potential for the reduction of Co(III)-HoSF is 42 mV more positive than that of the ascorbic acid reaction, while the standard potential of Mn(III)-HoSF is 27 mV positive relative to AH2. Fe(2+) in solution with Co- and Mn-HoSF under anaerobic conditions was oxidized to form Fe(O)OH within the HoSF interior, resulting in partial displacement of the Co or Mn by iron.

Increased Plasma Levels of Heme Oxygenase-1 in Human Brucellosis.

PubMed

Chen, Zhe; Zhang, Yu-Xue; Fu, Dong-Wei; Gao, Qing-Feng; Ge, Feng-Xia; Liu, Wei-Hua

2016-08-01

Brucellosis is associated with inflammation and the oxidative stress response. Heme oxygenase-1 (HO-1) is a cytoprotective stress-responsive enzyme that has anti-inflammatory and anti-oxidant effects. Nevertheless, the role of HO-1 in human brucellosis has not yet been studied. The aim of this study was to examine the plasma levels of HO-1 in patients with brucellosis and to evaluate the ability of plasma HO-1 levels as an auxiliary diagnosis, a severity predictor, and a monitor for brucellosis treatments. A total of 75 patients with brucellosis were divided into the acute, subacute, chronic active, and chronic stable groups. An additional 20 volunteers were included as the healthy control group. The plasma HO-1 levels and other laboratory parameters were measured in all groups. Furthermore, the plasma levels of HO-1 in the acute group were compared before and after treatment. The plasma HO-1 levels were considerably increased in the acute (4.97 ± 3.55), subacute (4.98 ± 3.23), and chronic active groups (4.43 ± 3.00) with brucellosis compared to the healthy control group (1.03 ± 0.63) (p < 0.01). In the acute group, the plasma HO-1 levels in the post-treatment group (2.33 ± 2.39) were significantly reduced compared to the pre-treatment group (4.97 ± 3.55) (p < 0.01). On the other hand, the plasma HO-1 levels were higher in the chronic active group (4.43 ± 3.00) than the chronic stable group (2.74 ± 2.23) (p < 0.05). However, the plasma HO-1 levels in the chronic stable group (2.74 ± 2.23) remained higher than the levels in the healthy control group (1.03 ± 0.63) (p < 0.05). The HO-1 levels were positively correlated with the C-reactive protein (CRP) levels in patients with brucellosis (r = 0.707, p < 0.01). The plasma HO-1 levels can reflect patients' brucellosis status and may be used as a supplementary plasma marker for diagnosing brucellosis and monitoring its treatment.

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53.

PubMed

Choe, Yun-Jeong; Lee, Sun-Young; Ko, Kyung Won; Shin, Seok Joon; Kim, Ho-Shik

2014-03-01

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-α, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin‑3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-μ, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-μ reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI.

PubMed

Shen, Zonglin; Jiang, Linling; Yang, Shuran; Ye, Jing; Dai, Nan; Liu, Xiaoyan; Li, Na; Lu, Jin; Liu, Fang; Lu, Yi; Sun, Xuejin; Cheng, Yuqi; Xu, Xiufeng

2017-01-01

Previous work exhibited different brain grey matter volume (GMV) changes between patients with early adult onset depression (EOD, age 18-29) and later adult onset depression (LOD, age 30-44) by using 30-year-old as the cut-off age. To identify whether regional homogeneity (ReHo) changes are also different between EOD and LOD by using same cut-off age, we used resting-state functional magnetic resonance imaging (fMRI) to detect the abnormal ReHo between patients with EOD and LOD in the present study. Resting-state fMRI scans of 58 patients with EOD, 62 patients with LOD, 60 young healthy controls (HC), and 52 old HC were obtained. The ReHo approach was used to analyze the images. The ANOVA analysis revealed that the ReHo values in the frontoparietal, occipital, and cerebellar regions were significantly different among the four groups. Relative to patients with LOD, patients with EOD displayed significantly increased ReHo in the left precuneus, and decreased ReHo in the right fusiform. The ReHo values in the left precuneus and the right fusiform had no significant correlation with the score of the depression rating scale or illness duration in both patient subgroups. Compared to young HC, patients with EOD showed significantly increased ReHo in the right frontoparietal regions and the right calcarine. Furthermore, the increased ReHo in the right frontoparietal regions, right insula and left hippocampus, and decreased ReHo in the left inferior occipital gyrus, right middle occipital gyrus, left calcarine, and left supplementary motor area were observed in patients with LOD when compared to old HC. The ReHo of brain areas that were related to mood regulation was changed in the first-episode, drug-naive adult patients with MDD. Adult patients with EOD and LOD exhibited different ReHo abnormalities relative to each age-matched comparison group, suggesting that depressed adult patients with different age-onset might have different pathological mechanism.

Prompt HO2 formation following the reaction of OH with aromatic compounds under atmospheric conditions.

PubMed

Nehr, Sascha; Bohn, Birger; Wahner, Andreas

2012-06-21

The secondary formation of HO(2) radicals following OH + aromatic hydrocarbon reactions in synthetic air under normal pressure and temperature was investigated in the absence of NO after pulsed production of OH radicals. OH and HO(x) (=OH + HO(2)) decay curves were recorded using laser-induced fluorescence after gas-expansion. The prompt HO(2) yields (HO(2) formed without preceding NO reactions) were determined by comparison to results obtained with CO as a reference compound. This approach was recently introduced and applied to the OH + benzene reaction and was extended here for a number of monocyclic aromatic hydrocarbons. The measured HO(2) formation yields are as follows: toluene, 0.42 ± 0.11; ethylbenzene, 0.53 ± 0.10; o-xylene, 0.41 ± 0.08; m-xylene, 0.27 ± 0.06; p-xylene, 0.40 ± 0.09; 1,2,3-trimethylbenzene, 0.31 ± 0.06; 1,2,4-trimethylbenzene, 0.37 ± 0.09; 1,3,5-trimethylbenzene, 0.29 ± 0.08; hexamethylbenzene, 0.32 ± 0.08; phenol, 0.89 ± 0.29; o-cresol, 0.87 ± 0.29; 2,5-dimethylphenol, 0.72 ± 0.12; 2,4,6-trimethylphenol, 0.45 ± 0.13. For the alkylbenzenes HO(2) is the proposed coproduct of phenols, epoxides, and possibly oxepins formed in secondary reactions with O(2). In most product studies the only quantified coproducts were phenols whereas only a few studies reported yields of epoxides. Oxepins have not been observed so far. Together with the yields of phenols from other studies, the HO(2) yields determined in this work set an upper limit to the combined yields of epoxides and oxepins that was found to be significant (≤0.3) for all investigated alkylbenzenes except m-xylene. For the hydroxybenzenes the currently proposed HO(2) coproducts are dihydroxybenzenes. For phenol and o-cresol the determined HO(2) yields are matching the previously reported dihydroxybenzene yields, indicating that these are the only HO(2) forming reaction channels. For 2,5-dimethylphenol and 2,4,6-trimethylphenol no complementary product studies are available.

Can preoperative detrusor underactivity influence surgical outcomes of 120 W HPS vaporization of the prostate (PVP) or holmium laser enucleation of the prostate (HoLEP)? A serial 3-year follow-up study.

PubMed

Cho, Min Chul; Park, Juhyun; Kim, Jung Kwon; Cho, Sung Yong; Jeong, Hyeon; Oh, Seung-June; Paick, Jae-Seung; Son, Hwancheol

2018-01-01

To determine the influence of preoperative detrusor underactivity (DU) on serial long-term outcomes of HPS/PVP or HoLEP for LUTS/BPH, and to compare the influence between the two surgeries. A total of 382 men, who underwent 120W-HPS/PVP or HoLEP for LUTS/BPH and for whom 36-month follow-up data were available, were classified into four groups: HPS with DU (n = 145), HPS without DU (n = 44), HoLEP with DU (n = 105), and HoLEP without DU (n = 88). DU was defined as bladder contractility index of <100. Surgical outcomes were assessed at postoperative 6, 12, 24, and 36 months using IPSS, uroflowmetry, and serum PSA. All four groups maintained improvements in voiding symptom score (VSS), storage symptom score, total-IPSS, QOL index, maximum flow rate (Qmax), post-void residual urine volume (PVR), and bladder voiding efficiency (BVE) compared with baseline up to 3 years postoperatively. There were no significant differences in improvements of postoperative IPSS parameters including QOL index between men with and without DU throughout the follow-up period after HPS or HoLEP. In men with DU, there were no significant differences in improvements of postoperative QOL index, Qmax, PVR, or BVE between HPS and HoLEP groups throughout the follow-up period, except for VSS and total IPSS. Serum PSA reductions after HoLEP were greater than after PVP. Improvements in LUTS, Qmax, and BVE can maintain up to 3 years after HPS or HoLEP for LUTS/BPH, irrespective of the presence or absence of preoperative DU. Although HoLEP may provide more durable improvement of VS in men with DU than HPS, there seems to be no difference in improvement of QOL or Qmax or BVE between HPS and HoLEP. © 2017 Wiley Periodicals, Inc.

Infiltration of myeloid cells in the pregnant uterus is affected by heme oxygenase-1.

PubMed

Zhao, Hui; Kalish, Flora; Wong, Ronald J; Stevenson, David K

2017-01-01

Infiltrating myeloid cells in pregnant uteri play critical roles in the establishment of the placenta and maintenance of normal pregnancies. Their recruitment and proliferation are primarily mediated by the interactions of cytokines and chemokines secreted locally with their corresponding receptors. Heme oxygenase-1 (HO-1) has various physiologic properties that contribute to placental vascular development, with deficiencies in HO-1 associated with pregnancy disorders. Here, we investigated the effect of HO-1 on myeloid cell infiltration into pregnant uteri using a partial HO-1-deficient (Het, HO-1 +/- ) mouse model. With the use of flow cytometry, HO-1 was found predominantly expressed in circulating and uterine myeloid cells, specifically neutrophils and monocytes/macrophages. In pregnant Het uteri, the numbers of neutrophils and monocytes/macrophages were significantly reduced compared with pregnant wild-type (WT; HO-1 +/+ ) uteri. With the use of BrdU in vivo assays, HO-1 deficiency did not affect cell proliferation or blood cell populations. With the use of PCR arrays, gene expression of cytokines (Csf1, Csf3), chemokines (Ccl1, Ccl2, Ccl6, Ccl8, Ccl11, Ccl12, Cxcl4, Cxcl9, Cxcl12), and their receptors (Ccr1, Ccr2, Ccr3, Ccr5) were also reduced significantly in Het compared with pregnant WT uteri. Moreover, with the use of flow cytometry, myeloid CSF1R and CCR2 expression in blood and uteri from both pregnant and nonpregnant mice was characterized, and a deficiency in HO-1 significantly reduced CCR2 expression in infiltrating uterine monocytes/macrophages and dendritic cells (DCs). These data reveal that HO-1 regulates not only cytokine/chemokine production in pregnant uteri but also myeloid cell receptor numbers, suggesting a role of HO-1 in the recruitment and maintenance of myeloid cells in pregnant uteri and subsequent effects on placental vascular formation. © Society for Leukocyte Biology.

The Impact of Body Mass Index on Heterotopic Ossification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourad, Waleed Fouad, E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Department of Radiation Oncology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY

2012-04-01

Purpose: To analyze the impact of different body mass index (BMI) as a surrogate marker for heterotopic ossification (HO) in patients who underwent surgical repair (SR) for displaced acetabular fractures (DAF) followed by radiation therapy (RT). Methods and Materials: This is a single-institution retrospective study of 395 patients. All patients underwent SR for DAF followed by RT {+-} indomethacin. All patients received postoperative RT, 7 Gy, within 72 h. The patients were separated into four groups based on their BMI: <18.5, 18.5-24.9, 25-29.9, and >30. The end point of this study was to evaluate the efficacy of RT {+-} indomethacinmore » in preventing HO in patients with different BMI. Results: Analysis of BMI showed an increasing incidence of HO with increasing BMI: <18.5, (0%) 0/6 patients; 18.5-24.9 (6%), 6 of 105 patients developed HO; 25-29.9 (19%), 22 of 117; >30 (31%), 51 of 167. Chi-square and multivariate logistic regression analysis showed that the correlation between odds of HO and BMI is significant, p < 0.0001. As the BMI increased, the risk of HO and Brooker Classes 3, 4 HO increased. The risk of developing HO is 1.0 Multiplication-Sign (10%) more likely among those with higher BMI compared with those with lower BMI. For a one-unit increase in BMI the log odds of HO increases by 1.0, 95% CI (1.06-1.14). Chi-square test shows no significant difference among all other factors and HO (e.g., indomethacin, race, gender). Conclusions: Despite similar surgical treatment and prophylactic measures (RT {+-} indomethacin), the risk of HO appears to significantly increase in patients with higher BMI after DAF. Higher single-fraction doses or multiple fractions and/or combination therapy with nonsteroidal inflammatory drugs may be of greater benefit to these patients.« less

Compound C Stimulates Heme Oxygenase-1 Gene Expression via the Nrf2-ARE Pathway to Preserve Human Endothelial Cell Survival

PubMed Central

Liu, Xiao-ming; Peyton, Kelly J.; Shebib, Ahmad R.; Wang, Hong; Durante, William

2011-01-01

We recently identified adenosine monophosphate-activated protein kinase (AMPK) as a novel inducer of heme oxygenase-1 (HO-1) and surprisingly found that compound C (6-[4-(2-piperidin-1-yl-ethoxy)-phenyl]3-pyridin-4-yl-pyrazolo[1,5-a] pyrimidine), a cell-permeable inhibitor of AMPK, could also elevate HO-1 suggesting other AMPK-independent actions for this agent. In this study, we investigated the biochemical mechanism by which compound C stimulates HO-1 expression in human endothelial cells (ECs) and determined the biological significance of the induction of HO-1 by compound C in these cells. Compound C stimulated a concentration- and time-dependent increase in HO-1 expression and an increase in HO-1 promoter activity that was abrogated by mutating the antioxidant responsive elements (AREs) in the HO-1 promoter or by overexpressing a dominant negative mutant of NF-E2-related factor-2 (Nrf2). Compound C also stimulated Nrf2 expression and this was associated with an increase in the production of reactive oxygen species and with a decline in intracellular glutathione levels. Interestingly, the glutathione donor N-acetyl-L-cysteine or the NADPH oxidase inhibitor apocynin blocked the induction of HO-1 by compound C. Finally, compound C stimulated EC death and this was potentiated by silencing HO-1 expression and reversed by the administration of CO, biliverdin, or bilirubin. In conclusion, this study demonstrates that compound C stimulates HO-1 gene expression in human vascular endothelium via the activation of the Nrf2/ARE signaling pathway to counteract compound C-mediated cell death. The ability of compound C to induce HO-1 expression may contribute to the pleiotropic actions of this agent and suggest caution when using compound C to probe for AMPK functions. PMID:21635873

Heme oxygenase-1 gene expression modulates angiotensin II-induced increase in blood pressure.

PubMed

Yang, Liming; Quan, Shuo; Nasjletti, Alberto; Laniado-Schwartzman, Michal; Abraham, Nader G

2004-06-01

The heme-heme oxygenase (HO) system has been implicated in the regulation of vascular reactivity and blood pressure. This study examines the notion that overexpression of HO decreases pressor responsiveness to angiotensin II (Ang II). Five-day-old Sprague-Dawley rats received an intraleft ventricular injection of approximately 5x10(9) cfu/mL of retroviruses containing human HO-1 sense (LSN-HHO-1), rat HO-1 antisense (LSN-RHO-1-AS), or control retrovirus (LXSN). Three months later, rats were instrumented with femoral arterial and venous catheters for mean arterial pressure (MAP) determination and Ang II administration, respectively. Rats injected with LSN-HHO-1, but not with LXSN, expressed human HO-1 mRNA and protein in several tissues. BP increased with administration of Ang II in rats expressing and not expressing human HO-1. However, the Ang II-induced pressor response (mm Hg) in LSN-HHO-1 rats (16+/-3, 27+/-3, and 38+/-3 at 0.5, 2, and 10 ng) was surpassed (P<0.05) in LXSN rats (23+/-1, 37+/-2, and 52+/-2 at 0.5, 2, and 10 ng). Importantly, treating LSN-HHO-1 rats with the HO inhibitor tin mesoporphyrin (SnMP) enhanced (P<0.05) the Ang II-induced pressor response to a level not different from that observed in LXSN rats. Rats injected with LSN-RHO-1-AS showed a decrease in renal HO-1 protein expression and HO activity relative to control LXSN rats. Administration of Ang II (0.1 to 2 ng) caused small (4 to 5 mm Hg) but significant increases in MAP in rats injected with LSN-RHO-1-AS (P<0.05) compared with rats injected with LXSN. These data demonstrate that overexpression of HO-1 brings about a reduction in pressor responsiveness to Ang II, which is most likely due to increased generation of an HO-1 product, presumably CO, with the ability to inhibit vascular reactivity to constrictor stimuli.

FRED user's manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shilling, J.

1984-02-01

FRED, the friendly editor, is a screen-based structured editor. This manual is intended to serve the needs of a wide range of users of the FRED text editor. Most users will find it sufficient to read the introductory material in section 2, supplemented with the full command set description in section 3. Advanced users may wish to change the keystroke sequences which invoke editor commands. Section 4 describes how to change key bindings and how to define command macros. Some users may need to modify a language description or create an entirely new language description for use with FRED. Sectionmore » 5 describes the format of the language descriptions used by the editor, and describes how to construct a language grammar. Section 6 describes known portability problems of the FRED editor and should concern only system installation personnel. The editor points out syntax errors in the file being edited and does automatic pretty printing.« less

EDT mode for JED -- An advanced Unix text editor

NASA Astrophysics Data System (ADS)

McIlwrath, B. K.; Page, C. G.

This note describes Starlink extended EDT emulation for the JED editor. It provides a Unix text editor which can utilise the advanced facilities of DEC VTn00, xterm and similar terminals. JED in this mode provides a reasonably good emulation of the VAX/VMS editor EDT in addition to many extra facilities.

Becoming an Online Editor: Perceived Roles and Responsibilities of Wikipedia Editors

ERIC Educational Resources Information Center

Littlejohn, Allison; Hood, Nina

2018-01-01

Introduction: We report on the experiences of a group of people as they become Wikipedia editors. We test Benkler's (2002) theory that commons-based production processes accelerate the creation of capital, questioning what knowledge production processes do people engage in as they become editors? The analysis positions the development of editing…

Emerging Perspectives on Editorial Ethics: An Interview with Chris Higgins

ERIC Educational Resources Information Center

Jackson, Liz

2017-01-01

Chris Higgins took on the roles of Editor of "Educational Theory," and Editor-in-Chief of the "Philosophy of Education Yearbook" published by the Philosophy of Education Society, in 2013, after having been an Associate Editor and Book Review Editor for "Educational Theory" for six years. Higgins worked closely with…

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Romantic Resonances in the Rhetoric of Peter Elbow's "Writing Without Teachers."

ERIC Educational Resources Information Center

Yager, Kristi

1996-01-01

Seeks to uncover the historical roots within English Romanticism of Peter Elbow's thinking in order to show the depth and complexity of his assumptions about writing. Implicitly refutes charges questioning the intellectual credibility of Elbow's work. (TB)

Peter Andreas Hansen and the astronomical community - a first investigation of the Hansen papers. (German Title: Peter Andreas Hansen und die astronomische Gemeinschaft - eine erste Auswertung des Hansen-Nachlasses. )

NASA Astrophysics Data System (ADS)

Schwarz, Oliver; Strumpf, Manfred

The literary assets of Peter Andreas Hansen are deposited in the Staatsarchiv Hamburg, the Forschungs- und Landesbibliothek Gotha and the Thüringer Staatsarchiv Gotha. They were never systematically investigated. We present here some results of a first evaluation. It was possible to reconstruct the historical events with regard to the maintenance of the Astronomische Nachrichten and the Altona observatory in 1854. Hansen was a successful teacher for many young astronomers. His way of stimulating the evolution of astronomy followed Zach's tradition.

Ammonia promotes endothelial cell survival via the heme oxygenase-1-mediated release of carbon monoxide.

PubMed

Liu, Xiao-Ming; Peyton, Kelly J; Durante, William

2017-01-01

Although endothelial cells produce substantial quantities of ammonia during cell metabolism, the physiologic role of this gas in these cells is not known. In this study, we investigated if ammonia regulates the expression of heme oxygenase-1 (HO-1), and if this enzyme influences the biological actions of ammonia on endothelial cells. Exogenously administered ammonia, given as ammonium chloride or ammonium hydroxide, or endogenously generated ammonia stimulated HO-1 protein expression in cultured human and murine endothelial cells. Dietary supplementation of ammonia also induced HO-1 protein expression in murine arteries. The increase in HO-1 protein by ammonia in endothelial cells was first detected 4h after ammonia exposure and was associated with the induction of HO-1 mRNA, enhanced production of reactive oxygen species (ROS), and increased expression and activity of NF-E2-related factor-2 (Nrf2). Ammonia also activated the HO-1 promoter and this was blocked by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. The induction of HO-1 expression by ammonia was dependent on ROS formation and prevented by N-acetylcysteine or rotenone. Finally, prior treatment of endothelial cells with ammonia inhibited tumor necrosis factor-α-stimulated cell death. However, silencing HO-1 expression abrogated the protective action of ammonia and this was reversed by the administration of carbon monoxide but not bilirubin or iron. In conclusion, this study demonstrates that ammonia stimulates the expression of HO-1 in endothelial cells via the ROS-Nrf2 pathway, and that the induction of HO-1 contributes to the cytoprotective action of ammonia by generating carbon monoxide. Moreover, it identifies ammonia as a potentially important signaling gas in the vasculature that promotes endothelial cell survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiological cyclic strain promotes endothelial cell survival via the induction of heme oxygenase-1

PubMed Central

Liu, Xiao-ming; Peyton, Kelly J.

2013-01-01

Endothelial cells (ECs) are constantly subjected to cyclic strain that arises from periodic change in vessel wall diameter as a result of pulsatile blood flow. Application of physiological levels of cyclic strain inhibits EC apoptosis; however, the underlying mechanism is not known. Since heme oxygenase-1 (HO-1) is a potent inhibitor of apoptosis, the present study investigated whether HO-1 contributes to the antiapoptotic action of cyclic strain. Administration of physiological cyclic strain (6% at 1 Hz) to human aortic ECs stimulated an increase in HO-1 activity, protein, and mRNA expression. The induction of HO-1 was preceded by a rise in reactive oxygen species (ROS) and Nrf2 protein expression. Cyclic strain also stimulated an increase in HO-1 promoter activity that was prevented by mutating the antioxidant responsive element in the promoter or by overexpressing dominant-negative Nrf2. In addition, the strain-mediated induction of HO-1 and activation of Nrf2 was abolished by the antioxidant N-acetyl-l-cysteine. Finally, application of cyclic strain blocked inflammatory cytokine-mediated EC death and apoptosis. However, the protective action of cyclic strain was reversed by the HO inhibitor tin protoporphyrin-IX and was absent in ECs isolated from HO-1-deficient mice. In conclusion, the present study demonstrates that a hemodynamically relevant level of cyclic strain stimulates HO-1 gene expression in ECs via the ROS-Nrf2 signaling pathway to inhibit EC death. The ability of cyclic strain to induce HO-1 expression may provide an important mechanism by which hemodynamic forces promote EC survival and vascular homeostasis. PMID:23604711

The expression of heme oxygenase-1 and inducible nitric oxide synthase in aorta during the development of hypertension in spontaneously hypertensive rats.

PubMed

Cheng, Pao-Yun; Chen, Jin-Jer; Yen, Mao-Hsiung

2004-12-01

The aim of this study was to observe the time-course changes of heme oxygenase-1 (HO-1) and inducible nitric oxide synthase (iNOS) induction in aorta during the development of hypertension, as well as the relationship of HO-1/carbon monoxide (CO) system and iNOS/nitric oxide (NO) system in spontaneously hypertensive rats (SHR). The systolic blood pressure (SBP) was determined in conscious rats by the tail-cuff method. The tissue HO-1 and iNOS mRNA and protein levels were estimated with reverse transcription polymerase chain reaction and Western blot method. The expression of HO-1 and iNOS in aorta increased with the SBP elevation during the development of SHR and was attenuated when the hypertension was lowered with the vasodilator hydralazine. At 8 weeks, only HO-1 was induced, whereas at 12 and 16 weeks, both HO-1 and iNOS were observed. The level of plasma nitrite/nitrate was associated with the change in iNOS expression in SHR. In addition, the SBP of 8-week-old SHR was significantly increased after pretreatment with zinc protoporphyrin IX for 7 consecutive days. Chronic blockade of iNOS activity by aminoguanidine resulted in significant up-regulation of HO-1, but the pressor effect was blunt. These results suggest that the up-regulation of HO-1 and iNOS in aorta is a compensatory mechanism for the elevation of SBP during the development of hypertension in SHR. The expression of HO-1 is earlier than that of iNOS. Our data suggest that the HO-1/CO system takes over and acts as a major modulator for the regulation of SBP when the iNOS/NO system is suppressed.

Measurement of interferences associated with the detection of the hydroperoxy radical in the atmosphere using laser-induced fluorescence

NASA Astrophysics Data System (ADS)

Lew, Michelle M.; Dusanter, Sebastien; Stevens, Philip S.

2018-01-01

One technique used to measure concentrations of the hydroperoxy radical (HO2) in the atmosphere involves chemically converting it to OH by addition of NO and subsequent detection of OH. However, some organic peroxy radicals (RO2) can also be rapidly converted to HO2 (and subsequently OH) in the presence of NO, interfering with measurements of ambient HO2 radical concentrations. This interference must be characterized for each instrument to determine to what extent various RO2 radicals interfere with measurements of HO2 and to assess the impact of this interference on past measurements. The efficiency of RO2-to-HO2 conversion for the Indiana University laser-induced fluorescence-fluorescence assay by gas expansion (IU-FAGE) instrument was measured for a variety of RO2 radicals. Known quantities of OH and HO2 radicals were produced from the photolysis of water vapor at 184.9 nm, and RO2 radicals were produced by the reaction of several volatile organic compounds (VOCs) with OH. The conversion efficiency of RO2 radicals to HO2 was measured when NO was added to the sampling cell for conditions employed during several previous field campaigns. For these conditions, approximately 80 % of alkene-derived RO2 radicals and 20 % of alkane-derived RO2 radicals were converted to HO2. Based on these measurements, interferences from various RO2 radicals contributed to approximately 35 % of the measured HO2 signal during the Mexico City Metropolitan Area (MCMA) 2006 campaign (MCMA-2006), where the measured VOCs consisted of a mixture of saturated and unsaturated species. However, this interference can contribute more significantly to the measured HO2 signal in forested environments dominated by unsaturated biogenic emissions such as isoprene.

Downregulation of Heme Oxygenase 1 (HO-1) Activity in Hematopoietic Cells Enhances Their Engraftment After Transplantation.

PubMed

Adamiak, Mateusz; Moore, Joseph B; Zhao, John; Abdelbaset-Ismail, Ahmed; Grubczak, Kamil; Rzeszotek, Sylwia; Wysoczynski, Marcin; Ratajczak, Mariusz Z

2016-01-01

Heme oxygenase 1 (HO-1) is an inducible stress-response enzyme that not only catalyzes the degradation of heme (e.g., released from erythrocytes) but also has an important function in various physiological and pathophysiological states associated with cellular stress, such as ischemic/reperfusion injury. HO-1 has a well-documented anti-inflammatory potential, and HO-1 has been reported to have a negative effect on adhesion and migration of neutrophils in acute inflammation in a model of peritonitis. This finding is supported by our recent observation that hematopoietic stem progenitor cells (HSPCs) from HO-1 KO mice are easy mobilizers, since they respond better to peripheral blood chemotactic gradients than wild-type littermates. Based on these findings, we hypothesized that transient inhibition of HO-1 by nontoxic small-molecule inhibitors would enhance migration of HSPCs in response to bone marrow chemoattractants and thereby facilitate their homing. To directly address this issue, we generated several human hematopoietic cell lines in which HO-1 was upregulated or downregulated. We also exposed murine and human BM-derived cells to small-molecule activators and inhibitors of HO-1. Our results indicate that HO-1 is an inhibitor of hematopoietic cell migration in response to crucial BM homing chemoattractants such as stromal-derived factor 1 (SDF-1) and sphingosine-1-phosphate (S1P). Most importantly, our in vitro and in vivo animal experiments demonstrate for the first time that transiently inhibiting HO-1 activity in HSPCs by small-molecule inhibitors improves HSPC engraftment. We propose that this simple and inexpensive strategy could be employed in the clinical setting to improve engraftment of HSPCs, particularly in those situations in which the number of HSPCs available for transplant is limited (e.g., when transplanting umbilical cord blood).

Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors.

PubMed

Santa-Cruz, Diego; Pacienza, Natalia; Zilli, Carla; Pagano, Eduardo; Balestrasse, Karina; Yannarelli, Gustavo

2017-08-01

Heme oxygenase-1 (HO-1) plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs) in soybean plants subjected to ultraviolet-B (UV-B) radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15kJm-2 UV-B. A 304bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%). Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Heme oxygenase-1-derived bilirubin counteracts HIV protease inhibitor-mediated endothelial cell dysfunction

PubMed Central

Liu, Xiao-Ming; Durante, Zane E.; Peyton, Kelly J.; Durante, William

2016-01-01

The use of HIV protease inhibitors (PIs) has extended the duration and quality of life for HIV-positive individuals. However there is increasing concern that this antiviral therapy may promote premature cardiovascular disease by impairing endothelial cell (EC) function. In the present study, we investigated the effect of HIV PIs on EC function and determined if the enzyme heme oxygenase (HO-1) influences the biological action of these drugs. We found that three distinct PIs, including ritonavir, atazanavir, and lopinavir, stimulated the expression of HO-1 protein and mRNA. The induction of HO-1 was associated with an increase in NF-E2-related factor-2 (Nrf2) activity and reactive oxygen species (ROS). PIs also stimulated HO-1 promoter activity and this was prevented by mutating the antioxidant responsive element or by overexpressing dominant-negative Nrf2. In addition, the PI-mediated induction of HO-1 was abolished by N-acetyl-L-cysteine and rotenone. Furthermore, PIs blocked EC proliferation and migration and stimulated the expression of intercellular adhesion molecule-1 and the adhesion of monocytes on ECs. Inhibition of HO-1 activity or expression potentiated the anti-proliferative and inflammatory actions of PIs which was reversed by bilirubin but not carbon monoxide. Alternatively, adenovirus-mediated overexpression of HO-1 attenuated the growth-inhibitory and inflammatory effect of PIs. In contrast, blocking HO-1 activity failed to modify the anti-migratory effect of the PIs. Thus, induction of HO-1 via the ROS–Nrf2 pathway in human ECs counteracts the anti-proliferative and inflammatory actions of PIs by generating bilirubin. Therapeutic approaches targeting HO-1 may provide a novel approach in preventing EC dysfunction and vascular disease in HIV-infected patients undergoing antiretroviral therapy. PMID:26968795

Hypochlorous acid-induced heme oxygenase-1 gene expression promotes human endothelial cell survival

PubMed Central

Wei, Yong; Liu, Xiao-ming; Peyton, Kelly J.; Wang, Hong; Johnson, Fruzsina K.; Johnson, Robert A.

2009-01-01

Hypochlorous acid (HOCl) is a unique oxidant generated by the enzyme myeloperoxidase that contributes to endothelial cell dysfunction and death in atherosclerosis. Since myeloperoxidase localizes with heme oxygenase-1 (HO-1) in and around endothelial cells of atherosclerotic lesions, the present study investigated whether there was an interaction between these two enzymes in vascular endothelium. Treatment of human endothelial cells with the myeloperoxidase product HOCl stimulated a concentration- and time-dependent increase in HO-1 protein that resulted in a significant rise in carbon monoxide (CO) production. The induction of HO-1 protein was preceded by a prominent increase in HO-1 mRNA and total and nuclear factor-erythroid 2-related factor 2 (Nrf2). In addition, HOCl induced a significant rise in HO-1 promoter activity that was blocked by mutating the antioxidant response element (ARE) in the promoter or by overexpressing a dominant-negative mutant of Nrf2. The HOCl-mediated induction of Nrf2 or HO-1 was blocked by the glutathione donor N-acetyl-l-cysteine but was unaffected by ascorbic or uric acid. Finally, treatment of endothelial cells with HOCl stimulated mitochondrial dysfunction, caspase-3 activation, and cell death that was potentiated by the HO inhibitor, tin protoporphyrin-IX, or by the knockdown of HO-1, and reversed by the exogenous administration of biliverdin, bilirubin, or CO. These results demonstrate that HOCl induces HO-1 gene transcription via the activation of the Nrf2/ARE pathway to counteract HOCl-mediated mitochondrial dysfunction and cell death. The ability of HOCl to activate HO-1 gene expression may represent a critical adaptive response to maintain endothelial cell viability at sites of vascular inflammation and atherosclerosis. PMID:19625608

Design of metal cofactors activated by a protein–protein electron transfer system

PubMed Central

Ueno, Takafumi; Yokoi, Norihiko; Unno, Masaki; Matsui, Toshitaka; Tokita, Yuichi; Yamada, Masako; Ikeda-Saito, Masao; Nakajima, Hiroshi; Watanabe, Yoshihito

2006-01-01

Protein-to-protein electron transfer (ET) is a critical process in biological chemistry for which fundamental understanding is expected to provide a wealth of applications in biotechnology. Investigations of protein–protein ET systems in reductive activation of artificial cofactors introduced into proteins remains particularly challenging because of the complexity of interactions between the cofactor and the system contributing to ET. In this work, we construct an artificial protein–protein ET system, using heme oxygenase (HO), which is known to catalyze the conversion of heme to biliverdin. HO uses electrons provided from NADPH/cytochrome P450 reductase (CPR) through protein–protein complex formation during the enzymatic reaction. We report that a FeIII(Schiff-base), in the place of the active-site heme prosthetic group of HO, can be reduced by NADPH/CPR. The crystal structure of the Fe(10-CH2CH2COOH-Schiff-base)·HO composite indicates the presence of a hydrogen bond between the propionic acid carboxyl group and Arg-177 of HO. Furthermore, the ET rate from NADPH/CPR to the composite is 3.5-fold faster than that of Fe(Schiff-base)·HO, although the redox potential of Fe(10-CH2CH2COOH-Schiff-base)·HO (−79 mV vs. NHE) is lower than that of Fe(Schiff-base)·HO (+15 mV vs. NHE), where NHE is normal hydrogen electrode. This work describes a synthetic metal complex activated by means of a protein–protein ET system, which has not previously been reported. Moreover, the result suggests the importance of the hydrogen bond for the ET reaction of HO. Our Fe(Schiff-base)·HO composite model system may provide insights with regard to design of ET biosystems for sensors, catalysts, and electronics devices. PMID:16769893

Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.

PubMed

Foresti, Roberta; Bains, Sandip K; Pitchumony, Tamil Selvi; de Castro Brás, Lisandra E; Drago, Filippo; Dubois-Randé, Jean-Luc; Bucolo, Claudio; Motterlini, Roberto

2013-10-01

The nuclear factor erythroid derived 2-related factor 2 (Nrf2) and the antioxidant protein heme oxygenase-1 (HO-1) are crucial components of the cellular stress response. These two systems work together to combat oxidative stress and inflammation and are attractive drug targets for counteracting different pathologies, including neuroinflammation. We aimed to identify the most effective Nrf2/HO-1 activators that modulate the inflammatory response in microglia cells. In the present study, we searched the literature and selected 56 compounds reported to activate Nrf2 or HO-1 and analyzed them for HO-1 induction at 6 and 24h and cytotoxicity in BV2 microglial cells in vitro. Approximately 20 compounds up-regulated HO-1 at the concentrations tested (5-20 μM) with carnosol, supercurcumin, cobalt protoporphyrin-IX and dimethyl fumarate exhibiting the best induction/low cytotoxicity profile. Up-regulation of HO-1 by some compounds resulted in increased cellular bilirubin levels but did not augment the expression of proteins involved in heme synthesis (ALAS 1) or biliverdin reductase. Bilirubin production by HO-1 inducers correlated with their potency in inhibiting nitrite production after challenge with interferon-γ (INF-γ) or lipopolysaccharide (LPS). The compounds down-regulated the inflammatory response (TNF-α, PGE2 and nitrite) more strongly in cells challenged with INF-γ than LPS, and silencing HO-1 or Nrf2 with shRNA differentially affected the levels of inflammatory markers. These findings indicate that some small activators of Nrf2/HO-1 are effective modulators of microglia inflammation and highlight the chemical scaffolds that can serve for the synthesis of potent new derivatives to counteract neuroinflammation and neurodegeneration. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Reevaluation of Airborne HO(x) Observations from NASA Field Campaigns

NASA Technical Reports Server (NTRS)

Olson, Jennifer; Crawford, James H.; Chen, Gao; Brune, William H.; Faloona, Ian C.; Tan, David; Harder, Hartwig; Martinez, Monica

2006-01-01

In-situ observations of tropospheric HO(x) (OH and HO2) obtained during four NASA airborne campaigns (SUCCESS, SONEX, PEM-Tropics B and TRACE-P) are reevaluated using the NASA Langley time-dependent photochemical box model. Special attention is given to previously diagnosed discrepancies between observed and predicted HO2 which increase with higher NO(x) levels and at high solar zenith angles. This analysis shows that much of the model discrepancy at high NO(x) during SUCCESS can be attributed to modeling observations at time-scales too long to capture the nonlinearity of HO(x) chemistry under highly variable conditions for NO(x). Discrepancies at high NO(x) during SONEX can be moderated to a large extent by complete use of all available precursor observations. Differences in kinetic rate coefficients and photolysis frequencies available for previous studies versus current recommendations also explain some of the disparity. Each of these causes is shown to exert greater influence with increasing NO(x) due to both the chemical nonlinearity between HO(x) and NO(x) and the increased sensitivity of HO(x) to changes in sources at high NO(x). In contrast, discrepancies at high solar zenith angles will persist until an adequate nighttime source of HO(x) can be identified. It is important to note that this analysis falls short of fully eliminating the issue of discrepancies between observed and predicted HO(x) for high NO(x) environments. These discrepancies are not resolved with the above causes in other data sets from ground-based field studies. Nevertheless, these results highlight important considerations in the application of box models to observationally based predictions of HO(x) radicals.

Reduced caveolin-1 promotes hyper-inflammation due to abnormal heme oxygenase-1 localizationin LPS challenged macrophages with dysfunctional CFTR

PubMed Central

Zhang, Ping-Xia; Murray, Thomas S.; Villella, Valeria Rachela; Ferrari, Eleonora; Esposito, Speranza; D'Souza, Anthony; Raia, Valeria; Maiuri, Luigi; Krause, Diane S.; Egan, Marie E.; Bruscia, Emanuela M.

2013-01-01

We have previously reported that TLR4 signaling is increased in lipopolysaccharide (LPS) -stimulated Cystic Fibrosis (CF) macrophages (MΦs), contributing to the robust production of pro-inflammatory cytokines. The heme oxygenase (HO-1)/carbon monoxide (CO) pathway modulates cellular redox status, inflammatory responses, and cell survival. The HO-1 enzyme, together with the scaffold protein caveolin 1 (CAV-1), also acts as a negative regulator of TLR4 signaling in MΦs. Here, we demonstrate that in LPS-challenged CF MΦs, HO-1 does not compartmentalize normally to the cell surface and instead accumulates intracellularly. The abnormal HO-1 localization in CF MΦs in response to LPS is due to decreased CAV-1 expression, which is controlled by the cellular oxidative state, and is required for HO-1 delivery to the cell surface. Overexpression of HO-1 or stimulating the pathway with CO-releasing molecules (CORM2)enhancesCAV-1 expression in CF MΦs, suggesting a positive-feed forward loop between HO-1/CO induction and CAV-1 expression. These manipulations reestablished HO-1 and CAV-1 cell surface localization in CF MΦ's. Consistent with restoration of HO-1/CAV-1 negative regulation of TLR4 signaling, genetic or pharmacological (CORM2)-induced enhancement of this pathway decreased the inflammatory response of CF MΦs and CF mice treated with LPS. In conclusion, our results demonstrate that the counter-regulatory HO-1/CO pathway, which is critical in balancing and limiting the inflammatory response, is defective in CF MΦs through a CAV-1-dependent mechanism, exacerbating the CF MΦ's response to LPS. This pathway could be a potential target for therapeutic intervention for CF lung disease. PMID:23606537

Authors and editors assort on gender and geography in high-rank ecological publications

PubMed Central

Belou, Rebecca M.

2018-01-01

Peer-reviewed publication volume and caliber are widely-recognized proxies for academic merit, and a strong publication record is essential for academic success and advancement. However, recent work suggests that publication productivity for particular author groups may also be determined in part by implicit biases lurking in the publication pipeline. Here, we explore patterns of gender, geography, and institutional rank among authors, editorial board members, and handling editors in high-impact ecological publications during 2015 and 2016. A higher proportion of lead authors had female first names (33.9%) than editorial board members (28.9%), and the proportion of female first names among handling editors was even lower (21.1%). Female editors disproportionately edited publications with female lead authors (40.3% of publications with female lead authors were handled by female editors, though female editors handled only 34.4% of all studied publications). Additionally, ecological authors and editors were overwhelmingly from countries in the G8, and high-ranking academic institutions accounted for a large portion of both the published work, and its editorship. Editors and lead authors with female names were typically affiliated with higher-ranking institutions than their male peers. This description of author and editor features provides a baseline for benchmarking future trends in the ecological publishing culture. PMID:29420647

Authors and editors assort on gender and geography in high-rank ecological publications.

PubMed

Manlove, Kezia R; Belou, Rebecca M

2018-01-01

Peer-reviewed publication volume and caliber are widely-recognized proxies for academic merit, and a strong publication record is essential for academic success and advancement. However, recent work suggests that publication productivity for particular author groups may also be determined in part by implicit biases lurking in the publication pipeline. Here, we explore patterns of gender, geography, and institutional rank among authors, editorial board members, and handling editors in high-impact ecological publications during 2015 and 2016. A higher proportion of lead authors had female first names (33.9%) than editorial board members (28.9%), and the proportion of female first names among handling editors was even lower (21.1%). Female editors disproportionately edited publications with female lead authors (40.3% of publications with female lead authors were handled by female editors, though female editors handled only 34.4% of all studied publications). Additionally, ecological authors and editors were overwhelmingly from countries in the G8, and high-ranking academic institutions accounted for a large portion of both the published work, and its editorship. Editors and lead authors with female names were typically affiliated with higher-ranking institutions than their male peers. This description of author and editor features provides a baseline for benchmarking future trends in the ecological publishing culture.

EGR-1 regulates Ho-1 expression induced by cigarette smoke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Huaqun, E-mail: chenhuaqun@njnu.edu.cn; Wang, Lijuan; Gong, Tao

2010-05-28

As an anti-oxidant molecule, heme oxygenase-1 (HO-1) has been implicated in the protection of lung injury by cigarette smoke (CS). The mechanisms regulating its expression have not been defined. In this report, the role of early growth response 1 (EGR-1) in the regulation of Ho-1 expression was investigated. In C57BL/6 mice with CS exposure, HO-1 was greatly increased in bronchial epithelial cells and alveolar inflammatory cells. In primary cultured mouse lung fibroblasts and RAW264.7 cells exposed to cigarette smoke water extract (CSE), an increase in HO-1 protein level was detected. In addition, CSE induced HO-1 expression was decreased in Egr-1more » deficient mouse embryo fibroblasts (Egr-1{sup -/-} MEFs). Nuclear localization of EGR-1 was examined in mouse lung fibroblasts after exposure to CSE. Luciferase reporter activity assays showed that the enhancer region of the Ho-1 gene containing a proposed EGR-1 binding site was responsible for the induction of HO-1. A higher increase of alveolar mean linear intercept (Lm) was observed in lung tissues, and a larger increase in the number of total cells and monocytes/macrophages from bronchial alveolar lavage fluid was found in CS-exposed mice by loss of function of EGR-1 treatment. In summary, the present data demonstrate that EGR-1 plays a critical role in HO-1 production induced by CS.« less

Management of oxidative stress by heme oxygenase-1 in cisplatin-induced toxicity in renal tubular cells.

PubMed

Schaaf, G J; Maas, R F M; de Groene, E M; Fink-Gremmels, J

2002-08-01

Induction of heme oxygenase-1 (HO-1) may serve as an immediate protective response during treatment with the cytostatic drug cisplatin (CDDP). Oxidative pathways participate in the characteristic nephrotoxicity of CDDP. In the present study, cultured tubular cells (LLC-PK1) were used to investigate whether induction of HO provided protection against CDDP by maintaining the cellular redox balance. The antioxidants, alpha-tocopherol (TOCO) and N-acetylcysteine (NAC), were used to demonstrate that elevation of ROS levels contribute to the development of CDDP-induced cytotoxicity. Chemical modulators of HO activity were used to investigate the role of HO herein. Hemin was used to specifically induce HO-1, while exposure of the cells to tin-protoporphyrin (SnPP) was shown to inhibit HO activity. Hemin treatment prior to CDDP-exposure significantly decreased the generation of ROS to control levels, while inhibition of HO increased the ROS levels beyond the levels measured in cells treated with CDDP alone. Furthermore, HO induction protected significantly against the cytotoxicity of CDDP, although this protection was limited. Similar results were obtained when the cells were preincubated with TOCO, suggesting that mechanisms other than impairment of the redox ratio are important in CDDP-induced loss of cell viability in vitro. In addition, SnPP treatment exacerbated the oxidative response and cytotoxicity of CDDP, especially at low CDDP concentrations. We therefore conclude that HO is able to directly limit the CDDP-induced oxidative stress response and thus serves as safeguard of the cellular redox balance.

Holmium laser lithotripsy (HoLL) of ureteral calculi

NASA Astrophysics Data System (ADS)

Kuntz, Rainer M.; Lehrich, Karin; Fayad, Amr

2001-05-01

The effectiveness and side effects of ureteroscopic HoLL of ureteral stones should be evaluated. In 63 patients (17 female, 46 males) a total of 75 stones of 3-20 mm diameter were treated with ureteroscopic HoLL. 18.7 percent of stones were located in the proximal third, 24.0 percent in the middle third and 57.3 percent in the distal third of the ureter. HoLL was performed with small diameter semirigid and flexible ureteroscopes, 220 or 365 nm flexible laser fibers and a holmium:YAG laser at a power of 5-15 W (0.5-1.0 J, 10- 15 Hz). 47 of 63 patients (74.6 percent) were immediately free of stones, and 8 others (12.6 percent) lost their residual fragments spontaneously within two weeks. Another 2 patients received additional chmolitholysis for uric acid stone fragments, i.e. 90.5 percent of patients were stone free by one sitting of ureterscopic HoLL. Of the remaining 6 patients (9.5 percent) who still had residual calculi 4 weeks after HoLL, 2 asymptomatic patients refused any additional treatment, 2 patients preferred treatment with ESWL, and 2 patients had a successful second HoLL, thereby raising the success rate of ureteroscopic HoLL to 93.7 percent. 2 patients showed contrast medium extravasation on retrograde ureterograms, due to guide wire perforation. No ureteral stricture occurred. In conclusion, transurethral ureteroscopic HoLL proved to be a safe and successful minimal invasive treatment of ureteral calculi.

Hydroxylated and methyl sulfone PCB metabolites in adipose and whole blood of polar bear (Ursus maritimus) from East Greenland.

PubMed

Sandala, G M; Sonne-Hansen, C; Dietz, R; Muir, D C G; Valters, K; Bennett, E R; Born, E W; Letcher, R J

2004-09-20

Persistent methyl sulfone (MeSO2-) and hydroxylated (HO-) polychlorinated biphenyl (PCB) metabolites have emerged as important classes of environmental contaminants in vertebrate, aquatic biota and humans. In the present study, PCB, MeSO2-PCB and HO-PCB concentrations and congener patterns were determined in the whole blood and adipose tissue of male (n = 7) and female (n = 12) polar bears (Ursus maritimus) of random age (3-25 years of age), and collected in 1999-2001 from the Ittoqqortoormiit/Scoresby Sound area in central East Greenland. There was no significant difference (P < 0.05) between males and females with respect to PCB or PCB metabolite concentrations in either tissue. The mean sum (Sigma) PCB concentrations were 7020+/-3366 ng/g lipid weight (lw) (range 2708-18148 ng/g lw) and 46.1+/-44.6 ng/g wet weight (ww) (range 12.6-204.2 ng/g ww) in adipose and blood, respectively. The mean Sigma-HO-PCB concentration in whole blood was 182.3+/-72.1 ng/g ww (range 93.8-382.1 ng/g ww). The mean Sigma-HO-PCB to Sigma-PCB concentration ratios in whole blood were 4.59+/-3.58 (range 1.03-11.88) and 8.30+/-5.56 (range 2.16-19.47) in females and males, respectively, which are the highest ratios reported so far for polar bears from any population, or for any free-ranging animal. Sigma-HO-PCB concentrations were greater than all other major classes of organochlorines (i.e. Sigma-PCBs, Sigma-MeSO2-PCBs, Sigma-chlordanes (CHLs), Sigma-hexachlorocyclohexanes (HCHs) and Sigma-chlorobenzenes (CBzs). The mean Sigma-MeSO2-PCB concentrations were 699+/-836 ng/g lw (range 127-3920 ng/g lw) and 10.9+/-9.6 ng/g ww (range 4.3-52.1 ng/g ww) in the adipose and blood, respectively. Regardless of age and sex, in both adipose and whole blood the MeSO2-PCB congener pattern was dominated by 3'- and 4'-MeSO2-CB101 and -CB87, and 4-MeSO2-CB149 (approx. 70% of the Sigma-MeSO2-PCBs). Minor differences in the MeSO2-PCB congener pattern were observed between blood and adipose, which suggests the possible influence of metabolite structure on mobilization and/or deposition to the adipose tissue. Sixteen HO-PCB congeners and one di-HO-PCB congener were identified, and five HO-PCB isomers and one di-HO-PCB isomer were detected. However, congener patterns were dominated by 4'-OH-CB120, 4-HO-CB146/3-HO-CB153, 4-OH-CB187, 4'-HO-CB172, 4-HO-CB193 and 4,4'-di-HO-CB202 (> 10 ng/g ww). HO-PCB congener patterns in whole blood were not significantly different (P < 0.05) between males and females. Other chlorinated phenolic contaminants, pentachlorophenol (0.3+/-0.3 ng/g ww) and 4-HO-heptachlorostyrene (7.5+/-2.9 ng/g ww) were also detected in blood. To our knowledge, this is to first report comparing PCBs, MeSO2-PCBs and HO-PCBs in whole blood and adipose tissue in a free-ranging wildlife species. HO-PCBs and MeSO2-PCBs are both important circulating contaminants in polar bears from this eastern Greenland population. Given the known toxicities of PCB metabolites, this population of polar bear may be experiencing health risks due to exposure to a complex loading of organohalogen contaminants that include HO-PCB and MeSO2-PCB metabolites.

Effects of Remote Ischemic Preconditioning on Heme Oxygenase-1 Expression and Cutaneous Wound Repair

PubMed Central

Cremers, Niels A. J.; Wever, Kimberley E.; Wong, Ronald J.; van Rheden, René E. M.; Vermeij, Eline A.; van Dam, Gooitzen M.; Carels, Carine E.; Lundvig, Ditte M. S.; Wagener, Frank A. D. T. G.

2017-01-01

Skin wounds may lead to scar formation and impaired functionality. Remote ischemic preconditioning (RIPC) can induce the anti-inflammatory enzyme heme oxygenase-1 (HO-1) and protect against tissue injury. We aim to improve cutaneous wound repair by RIPC treatment via induction of HO-1. RIPC was applied to HO-1-luc transgenic mice and HO-1 promoter activity and mRNA expression in skin and several other organs were determined in real-time. In parallel, RIPC was applied directly or 24h prior to excisional wounding in mice to investigate the early and late protective effects of RIPC on cutaneous wound repair, respectively. HO-1 promoter activity was significantly induced on the dorsal side and locally in the kidneys following RIPC treatment. Next, we investigated the origin of this RIPC-induced HO-1 promoter activity and demonstrated increased mRNA in the ligated muscle, heart and kidneys, but not in the skin. RIPC did not change HO-1 mRNA and protein levels in the wound 7 days after cutaneous injury. Both early and late RIPC did not accelerate wound closure nor affect collagen deposition. RIPC induces HO-1 expression in several organs, but not the skin, and did not improve excisional wound repair, suggesting that the skin is insensitive to RIPC-mediated protection. PMID:28218659

Nervous system disruption and concomitant behavioral abnormality in early hatched pufferfish larvae exposed to heavy oil.

PubMed

Kawaguchi, Masahumi; Sugahara, Yuki; Watanabe, Tomoe; Irie, Kouta; Ishida, Minoru; Kurokawa, Daisuke; Kitamura, Shin-Ichi; Takata, Hiromi; Handoh, Itsuki C; Nakayama, Kei; Murakami, Yasunori

2011-08-01

Spills of heavy oil (HO) over the oceans have been proven to have an adverse effect on marine life. It has been hypothesized that exposure of early larvae of sinking eggs to HO leads largely to normal morphology, whereas abnormal organization of the developing neural scaffold is likely to be found. HO-induced disruption of the nervous system, which controls animal behavior, may in turn cause abnormalities in the swimming behavior of hatched larvae. To clarify the toxicological effects of HO, we performed exposure experiments and morphological and behavioral analyses in pufferfish (Takifugu rubripes) larvae. Fertilized eggs of pufferfish were exposed to 50 mg/L of HO for 8 days and transferred to fresh seawater before hatching. The hatched larvae were observed for their swimming behavior, morphological appearance, and construction of muscles and nervous system. In HO-exposed larvae, we did not detect any anomaly of body morphology. However, they showed an abnormal swimming pattern and disorganized midbrain, a higher center controlling movement. Our results suggest that HO-exposed fishes suffer developmental disorder of the brain that triggers an abnormal swimming behavior and that HO may be selectively toxic to the brain and cause physical disability throughout the life span of these fishes.

Heme oxygenase-1 regulates mitochondrial quality control in the heart

PubMed Central

Hull, Travis D.; Boddu, Ravindra; Guo, Lingling; Tisher, Cornelia C.; Traylor, Amie M.; Patel, Bindiya; Joseph, Reny; Prabhu, Sumanth D.; Suliman, Hagir B.; Piantadosi, Claude A.; George, James F.

2016-01-01

The cardioprotective inducible enzyme heme oxygenase-1 (HO-1) degrades prooxidant heme into equimolar quantities of carbon monoxide, biliverdin, and iron. We hypothesized that HO-1 mediates cardiac protection, at least in part, by regulating mitochondrial quality control. We treated WT and HO-1 transgenic mice with the known mitochondrial toxin, doxorubicin (DOX). Relative to WT mice, mice globally overexpressing human HO-1 were protected from DOX-induced dilated cardiomyopathy, cardiac cytoarchitectural derangement, and infiltration of CD11b+ mononuclear phagocytes. Cardiac-specific overexpression of HO-1 ameliorated DOX-mediated dilation of the sarcoplasmic reticulum as well as mitochondrial disorganization in the form of mitochondrial fragmentation and increased numbers of damaged mitochondria in autophagic vacuoles. HO-1 overexpression promotes mitochondrial biogenesis by upregulating protein expression of NRF1, PGC1α, and TFAM, which was inhibited in WT animals treated with DOX. Concomitantly, HO-1 overexpression inhibited the upregulation of the mitochondrial fission mediator Fis1 and resulted in increased expression of the fusion mediators, Mfn1 and Mfn2. It also prevented dynamic changes in the levels of key mediators of the mitophagy pathway, PINK1 and parkin. Therefore, these findings suggest that HO-1 has a novel role in protecting the heart from oxidative injury by regulating mitochondrial quality control. PMID:27110594

Low temperature specific heat of frustrated antiferromagnet HoInCu4

NASA Astrophysics Data System (ADS)

Weickert, Franziska; Fritsch, Veronika; Bambaugh, Ryan; Sarrao, John; Thompson, Joe D.; Movshovich, Roman

2014-03-01

We present low temperature specific heat measurements of single crystal HoInCu4, down to 35 mK and in magnetic field up to 12 Tesla. Ho atoms are arranged in an FCC lattice of the edge-sharing tetrahedra, and undergo an antiferromagnetic ordering at TN = 0.76 K, with the frustration parameter f = -ΘCW /TN of 14.3. Magnetic AF order is suppressed in field H0 ~ 4 T. The low temperature Schottky anomaly due to Ho evolves smoothly as a function of field through H0 and TN. The peak value of the anomaly remains roughly constant from 0 T to 12 T. The temperature of the anomaly's peak remains constant at TSch ~ 170 mK for H

Suspected hypertrophic osteopathy in an ancient canid: Differential diagnosis of possible etiologies.

PubMed

Lawler, Dennis F; Reetz, Jennifer A; Sackman, Jill E; Evans, Richard H; Widga, Christopher

2015-06-01

Hypertrophic osteopathy (HO) has been reported in numerous mammalian species, but no reports address the range of conditions that can lead to HO, or the implications of those conditions, for archaeological diagnosis. We describe suspected HO from skeletal remains of an ancient large domestic dog recovered in Iowa, USA, at the Cherokee Sewer site. Canid remains from this site date 7430-7020calBP. The site is believed to have been a temporary, low-intensity campsite where bison were procured. Over 100 specimens from two small dogs, two large dogs, and a coyote, are present in the archaeofaunal assemblage. We document five pathological metapodials; an affected left ulna, radius, tuber calcaneus, accessory carpal, radial carpal; and an affected right central, second, and third tarsal within in a proliferative mass. HO was suspected based on gross morphology, radiography, and computed tomography. HO is a paraneoplastic syndrome with undetermined underlying pathogenesis; neuroendocrine complication of a number of neoplastic and non-neoplastic diseases is suspected. We review known disease associations of HO to provide a balanced field for considering differential diagnosis of suspect archaeological specimens, and suggest that definitive diagnosis of HO, or suspected HO, may be impossible in many instances where only skeletal remains are available for study. Copyright © 2015 Elsevier Inc. All rights reserved.

Tuning into single-band red upconversion luminescence in Yb(3+)/Ho(3+) activated nano-glass-ceramics through Ce(3+) doping.

PubMed

Chen, Daqin; Zhou, Yang; Wan, Zhongyi; Ji, Zhenguo; Huang, Ping

2015-03-28

Yb(3+)/Ho(3+) activated glass ceramics containing β-YF3 nanocrystals were successfully fabricated. The green ((5)S2/(5)F4→(5)I8) upconversion emission is dominant in the glass ceramics and is about 160 times stronger than that of the precursor glass, resulting from the partition of lanthanide activators into a low-phonon-energy crystalline lattice and the subsequent low probability of multi-phonon nonradiative relaxation from the (5)S2/(5)F4 and (5)I6 states to the lower ones. Upon the introduction of Ce(3+) ions into nano-glass-ceramics, two efficient cross-relaxation processes between Ho(3+) and Ce(3+), i.e., Ho(3+):(5)S2/(5)F4 + Ce(3+):(2)F5/2→Ho(3+):(5)F5 + Ce(3+):(2)F7/2 and Ho(3+):(5)I6 + Ce(3+):(2)F5/2→Ho(3+):(5)I7 + Ce(3+):(2)F7/2, are demonstrated to greatly suppress the population of the green-emitting (5)S2/(5)F4 state and to enhance the population of the red-emitting (5)F5 one, leading to the intense single-band red UC radiation of Ho(3+).

Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application.

PubMed

Zielhuis, S W; Nijsen, J F W; de Roos, R; Krijger, G C; van Rijk, P P; Hennink, W E; van het Schip, A D

2006-03-27

Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising systems for the treatment of liver malignancies. The microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method. After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. In this paper, the aspects of the production of a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10 patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS production process (sieving procedure, temperature control during evaporation and raw materials) were considered and the pharmaceutical quality of the microspheres was evaluated. The pharmaceutical characteristics (residual solvents, possible bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were in compliance with the requirements of the European Pharmacopoeia. Moreover, neutron irradiated Ho-PLLA-MS retained their morphological integrity and the holmium remained stably associated with the microspheres; it was observed that after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS which are produced as described in this paper, can be clinically applied, with respect to their pharmaceutical quality.

Characterization of low temperature metallic magnetic calorimeters having gold absorbers with implanted 163Ho ions

NASA Astrophysics Data System (ADS)

Gastaldo, L.; Ranitzsch, P. C.-O.; von Seggern, F.; Porst, J.-P.; Schäfer, S.; Pies, C.; Kempf, S.; Wolf, T.; Fleischmann, A.; Enss, C.; Herlert, A.; Johnston, K.

2013-05-01

For the first time we have investigated the behavior of fully micro-fabricated low temperature metallic magnetic calorimeters (MMCs) after undergoing an ion-implantation process. This experiment had the aim to show the possibility to perform a high precision calorimetric measurement of the energy spectrum following the electron capture of 163Ho using MMCs having the radioactive 163Ho ions implanted in the absorber. The isotope 163Ho decays through electron capture to 163Dy and features the smallest known QEC value. This peculiarity makes 163Ho a very interesting candidate to investigate the value of the electron neutrino mass by the analysis of the energy spectrum. The implantation of 163Ho ions was performed at ISOLDE-CERN. The performance of a detector that underwent an ion-implantation process is compared to the one of a detector without implanted ions. The results show that the implantation dose of ions used in this experiment does not compromise the properties of the detector. Moreover the performance of the detector prototype having the 163Ho ions implanted in the absorber is already close to the requirements needed for an experiment with sub-eV sensitivity to the electron neutrino mass. Based on these results, an optimized detector design for future 163Ho experiments is presented.

Heme oxygenase/carbon monoxide signaling pathways: regulation and functional significance.

PubMed

Ryter, Stefan W; Otterbein, Leo E; Morse, Danielle; Choi, Augustine M K

2002-01-01

Carbon monoxide (CO), a gaseous second messenger, arises in biological systems during the oxidative catabolism of heme by the heme oxygenase (HO) enzymes. HO exists as constitutive (HO-2, HO-3) and inducible isoforms (HO-1), the latter which responds to regulation by multiple stress-stimuli. HO-1 confers protection in vitro and in vivo against oxidative cellular stress. Although the redox active compounds that are generated from HO activity (i.e. iron, biliverdin-IXalpha, and bilirubin-IXa) potentially modulate oxidative stress resistance, increasing evidence points to cytoprotective roles for CO. Though not reactive, CO regulates vascular processes such as vessel tone, smooth muscle proliferation, and platelet aggregation, and possibly functions as a neurotransmitter. The latter effects of CO depend on the activation of guanylate cyclase activity by direct binding to the heme moiety of the enzyme, stimulating the production of cyclic 3':5'-guanosine monophosphate. CO potentially interacts with other intracellular hemoprotein targets, though little is known about the functional significance of such interactions. Recent progress indicates that CO exerts novel anti-inflammatory and anti-apoptotic effects dependent on the modulation of the p38 mitogen activated protein kinase (MAPK)-signaling pathway. By virtue of these effects, CO confers protection in oxidative lung injury models, and likely plays a role in HO-1 mediated tissue protection.

Analysis of bone-cartilage-stromal progenitor populations in trauma induced and genetic models of heterotopic ossification

PubMed Central

Agarwal, Shailesh; Loder, Shawn; Li, Shuli; Shrestha, Swati; Li, Jon; Zhao, Bin; Mishina, Yuji; James, Aaron; Levi, Benjamin

2016-01-01

Heterotopic ossification (HO), the formation of extra-skeletal bone in soft tissues, is a pathologic process occurring after substantial burns or trauma, or in patients with type I bone morphogenetic protein (BMP) receptor hyperactivating mutations. Identifying the cells responsible for de novo bone formation during adulthood is of critical importance for therapeutic and regenerative purposes. Using a model of trauma-induced HO with hindlimb Achilles’ tenotomy and dorsal burn injury and a genetic non-trauma HO model (Nfatc1-Cre/caAcvr1fl/wt), we demonstrate enrichment of previously defined bone-cartilage-stromal progenitor cells (BCSP: AlphaV+/CD105+/Tie2-/CD45-/Thy1-/6C3-) at the site of HO formation when compared with marrow isolated from the ipsilateral hindlimb, or from tissue of the contralateral, uninjured hindlimb. Upon transplantation into tenotomy sites soon after injury, BCSPs isolated from neonatal mice or developing HO incorporate into the developing lesion in cartilage and bone and express chondrogenic and osteogenic transcription factors. Additionally, BCSPs isolated from developing HO similarly incorporate into new HO lesions upon transplantation. Finally, adventitial cells, but not pericytes, appear to play a supportive role in HO formation. Our findings indicate that BCSPs contribute to de novo bone formation during adulthood and may hold substantial regenerative potential. PMID:27068890

HO:LULF and HO:LULF Laser Materials

NASA Technical Reports Server (NTRS)

Barnes, Norman P. (Inventor); Morrison, Clyde A. (Inventor); Filer, Elizabeth D. (Inventor); Jani, Mahendra G. (Inventor); Murray, Keith E. (Inventor); Lockard, George E. (Inventor)

1998-01-01

A laser host material LULF (LuLiF4) is doped with holmium (Ho) and thulium (Tm) to produce a new laser material that is capable of laser light production in the vicinity of 2 microns. The material provides an advantage in efficiency over conventional Ho lasers because the LULF host material allows for decreased threshold and upconversion over such hosts as YAG and YLF. The addition of Tm allows for pumping by commonly available GaAlAs laser diodes. For use with flashlamp pumping, erbium (Er) may be added as an additional dopant. For further upconversion reduction, the Tm can be eliminated and the Ho can be directly pumped.

Urbanization and Insurgency: The Turkish Case, 1976-1980

DTIC Science & Technology

1991-01-01

Political Socialization of West German Terrorism," in Peter Merkl (ed.), Political Violence and Terror, University of California Press, Berkeley...25, 1987. Wasmund, Klaus, "The Political Socialization of West German Terrorism," in Peter Merki (ed.), Political Violence and Terror, University of

Systemic Thinking: Enhancing Intelligence Preparation and Estimates

DTIC Science & Technology

2010-04-30

informally based on previous combat experience of the staff participants. 47 Peter Checkland , Systems Thinking, Systems Practice (John Wiley & Sons...Deparment, 2009, 3-5; http://journals.isss.org/index.php/proceedings52nd/article/view/1032/322 (accessed 23 March 2010). Checkland , Peter

Evaluation of Night Vision Devices for Image Fusion Studies

DTIC Science & Technology

2004-12-01

July 2004. http://www.sensorsmag.com/articles/0400/34/main.shtml Task, Harry L., Hartman, Richard T., Marasco , Peter L., Methods for Measuring...Press, Bellingham, Washington, 1998. Burt, Peter J. & Kolczynski, Raymond J., David Sarnoff Research Center, Enhanced Image Capture through Fusion

78 FR 38337 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

...) 90 Hennepin Avenue, Minneapolis, Minnesota 55480-0291: 1. Peter F. Lindholm, Long Lake, Minnesota, individually and as trustee of Peter F. Lindholm 2012 Irrevocable trust; to retain voting shares of Maple Banc...

75 FR 52534 - Su Van Ho: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

... Salmonella bacteria, with verification of such exportation or destruction by FDA. Mr. Ho concealed and... with Salmonella bacteria. As a result of his conviction, on June 10, 2010, FDA sent Mr. Ho a notice by...

Preparing Students To Work on Newspaper Copy Desks: Are Educators Meeting Editors' Expectations?

ERIC Educational Resources Information Center

Auman, Ann E.; Cook, Betsy B.

A study surveyed two groups in the fall of 1994, journalism educators and newspaper editors. Educators completed a survey regarding the course content and skill areas emphasized in beginning level copy editing courses, while editors were asked to respond to questions regarding the skills they expect entry-level copy editors to have. Respondents…

Web-Based Media Contents Editor for UCC Websites

NASA Astrophysics Data System (ADS)

Kim, Seoksoo

The purpose of this research is to "design web-based media contents editor for establishing UCC(User Created Contents)-based websites." The web-based editor features user-oriented interfaces and increased convenience, significantly different from previous off-line editors. It allows users to edit media contents online and can be effectively used for online promotion activities of enterprises and organizations. In addition to development of the editor, the research aims to support the entry of enterprises and public agencies to the online market by combining the technology with various UCC items.

Impacts of doping concentration on the saturable characteristics of Tm-Ho codoped fiber saturable absorber

NASA Astrophysics Data System (ADS)

Tao, Mengmeng; Feng, Guobin; Yu, Ting; Ye, Xisheng; Wang, Zhenbao; Shen, Yanlong; Zhao, Jun

2018-03-01

Impacts of Tm ion concentration and Ho ion concentration on the saturable behaviors of Tm-Ho codoped fiber saturable absorbers and the output characteristics of the passively Q-switched laser systems are investigated and analyzed both at the initial lasing state and the stable passive Q-switching state. Simulations show that, varying concentrations of Tm and Ho ions have different impacts on the temporal evolution processes but similar effects on the macroscopic characteristics of the laser system. The root for the impacts of dopant concentrations is the population of the 3H6 energy level and the cavity loss it induces. For Tm ions, the rise of the Tm concentration improves the population of the 3H6 energy level directly, while, for Ho ions, higher Ho concentration leads to larger recovery rate of the 3H6 energy level, thus increasing the population of the 3H6 energy level indirectly. As for limited total dopant concentration, the Tm:Ho concentration ratio can be optimized for different applications.

FAGE measurements of tropospheric HO with measurements and model of interferences

NASA Technical Reports Server (NTRS)

Hard, T. M.; Mehrabzadeh, A. A.; Chan, C. Y.; O'Brien, R. J.

1992-01-01

Ambient HO measurements by low-pressure laser-excited fluorescence with chemical modulation, and supporting ozone and water-vapor data, are presented for periods in May and August 1987. The observed peak daytime ambient HO concentrations are in the range (2.5 to 8) x 10 exp 6 molecules/cu cm and show small negative offsets due to photochemical interference. Direct measurements of the interference at fixed (O3) give the dependence on ambient (H2O) and on the modulating reagent (isobutane). At ambient (O3) = 30 ppb and 10 torr H2O, with excitation and detection at a total pressure of 4 torr, the net interference is equal to (HO) = -1.3 x 10 exp 6 molecules/cu cm. Production of HO by the reaction of isobutane with O(1D) accounts for the negative interference. Quenching of HO fluorescence by the modulating reagent contributes a smaller positive term to the interference; kinetic measurements of the quenching rate coefficient are reported. The experimental interference results are compared with a detailed kinetic model of HO production, excitation, relaxation, and detection; reasonable agreement is found.

Heterotopic ossification in civilians with lower limb amputations.

PubMed

Matsumoto, Mary E; Khan, Mohammed; Jayabalan, Prakash; Ziebarth, Jessica; Munin, Michael C

2014-09-01

To report the incidence of symptomatic heterotopic ossification (HO) in a defined civilian amputee population, describe its characteristics, and compare these findings to published data in military amputees. Retrospective chart analysis from July 1998 to July 2009. Ambulatory amputee clinic within a large university medical center. Adults with lower limb amputation (N=158). Not applicable. Patients with symptomatic HO confirmed by radiographs. A total of 261 patients were evaluated; 158 met inclusion criteria, with 59% having traumatic etiology, 18% vascular etiology, 22% infection, and 1% tumor. Symptomatic HO was diagnosed in 36 (22.8%) patients, and 94% patients had mild HO on radiographic scoring. Rate of HO in amputations related to trauma was not increased compared with those of other etiologies. Surgical resection of the ectopic bone was required in 4 (11%) patients. HO is seen commonly after civilian lower limb amputation regardless of etiology. The prevalence was less than that observed in previous reports from military populations. This is the first report estimating the prevalence of HO in adult civilian amputees. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Nitric oxide and iron modulate heme oxygenase activity as a long distance signaling response to salt stress in sunflower seedling cotyledons.

PubMed

Singh, Neha; Bhatla, Satish C

2016-02-29

Nitric oxide is a significant component of iron signaling in plants. Heme is one of the iron sensors in plants. Free heme is highly toxic and can cause cell damage as it catalyzes the formation of reactive oxygen species (ROS). Its catabolism is carried out by heme oxygenase (HOs; EC 1.14.99.3) which uses heme both as a prosthetic group and as a substrate. Two significant events, which accompany adaptation to salt stress in sunflower seedlings, are accumulation of ROS and enhanced production of nitric oxide (NO) in roots and cotyledons. Present investigations on the immunolocalization of heme oxygenase distribution in sunflower seedling cotyledons by confocal laser scanning microscopic (CLSM) imaging provide new information on the differential spatial distribution of the inducible form of HO (HO-1) as a long distance in response to NaCl stress. The enzyme is abundantly distributed in the specialized cells around the secretory canals (SCs) in seedling cotyledons. Abundance of tyrosine nitrated proteins has also been observed in the specialized cells around the secretory canals in cotyledons derived from salt stressed seedlings. The spatial distribution of tyrosine nitrated proteins and HO-1 expression further correlates with the abundance of mitochondria in these cells. Present findings, thus, highlight a link among distribution of HO-1 expression, abundance of tyrosine nitrated proteins and mitochondria in specialized cells around the secretory canal as a long distance mechanism of salt stress tolerance in sunflower seedlings. Enhanced spatial distribution of HO-1 in response to NaCl stress in seedling cotyledons is in congruence with the observed increase in specific activity of HO-1 in NaCl stressed conditions. The enzyme activity is further enhanced by hemin (HO-1 inducer) both in the absence or presence of NaCl stress and inhibited by zinc protoporphyrin. Western blot analysis of cotyledon homogenates using anti-HO-1 polyclonal antibody shows one major band (29 kDa) of HO-1. NaCl-modulated HO-1 activity correlates with endogenous NO content in the cotyledons. Increased NO accumulation by hemin treatment also correlates with enhanced activity of HO-1 in both control and NaCl stress conditions. Present work indicates that NO positively modulates HO-1 activity in sunflower seedling cotyledons. NaCl stress tends to antagonize NO action on HO-1 activity. NO (from sodium nitroprusside; SNP) is probably positively modulating HO-1 activity by way of its interaction/binding with heme group. Present work also shows enhanced NO accumulation in seedling cotyledons both in the absence or presence of iron in the growth medium, in response to NaCl stress. Thus, a probable link between endogenous NO, NaCl stress and iron-homeostasis by way of modulation of HO-1 activity at early stage of sunflower seedling growth has been proposed. Copyright © 2016 Elsevier Inc. All rights reserved.

Employee Attitudes of the Organizational Culture: Assessment of a TQM implementation Process

DTIC Science & Technology

1990-09-01

68 Analysis of Hypotheses..............70 Null Hypotheses Hola -Holi .............. 71 T-test...............................71 Summary of...Analyses for Hola -Holi 72 Null Hypotheses Ho2a-Ho2i .............. 73 One-way Analysis of Variance ......... 73 Summary of Analyses for Ho2a-Ho2i .... 77...supervisory and non- supervisory organizational members with regard to their attitudes about the organization’s quality culture. Hola . There will be no

Ho-nanoparticle-doping for improved high-energy laser fibers

NASA Astrophysics Data System (ADS)

Friebele, E. Joseph; Baker, Colin C.; Burdett, Ashley A.; Rhonehouse, Daniel L.; Bowman, Steven R.; Kim, Woohong; Sanghera, Jasbinder S.; Kucera, Courtney; Vargas, Amber; Ballato, John; Hemming, Alexander; Simakov, Nikita; Haub, John

2017-02-01

A significant issue for holmium-doped fiber lasers (HoDFLs) operating near 2 μm is multiphonon quenching due to the high phonon energy 1100 cm-1 of the silica host, which complicates power scaling due to reduced lifetimes and increased heating. Nanoparticle (NP) doping is a new technique where the structure surrounding the Ho ions is developed chemically prior to doping into the silica core. We have incorporated Ho3+ ions into various NPs, such as LaF3, Al2O3 and Lu2O3, to shield them from the silica glass matrix. Results indicate slightly longer lifetimes with Ho:LaF3 NPs and the possibility of further improvement with oxide NPs. We report the first of lasing in a Ho:Lu2O3 NP-doped fiber pumped at 1.95 μm and operating at 2.09 μm with a record slope efficiency of 85.2%.

77 FR 22320 - Findings of Research Misconduct

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Research Misconduct... Research Integrity (ORI) has taken final action in the following case: Peter J. Francis, M.D., Ph.D... Dr. Peter J. Francis, Associate Professor, Casey Eye Institute, OHSU, engaged in research misconduct...

ARC-2010-ACD10-0047-002

NASA Image and Video Library

2010-03-09

ARC Sculpture by Peter Gutkin 'Nice Ice in New York' circa 1970's. This sculputre was donated to Ames Research Center by the artist. Peter Gutkin has designed special interiors, exhibits, and display furniture for Ames since 1979. He currently maintains an office in San Francisco, CA.

Engineered Resilient Systems: Knowledge Capture and Transfer

DTIC Science & Technology

2014-08-29

development, but the work has not progressed significantly. 71 Peter Kall and Stein W. Wallace, Stochastic Programming, John Wiley & Sons, Chichester, 1994...John Wiley and Sons: Hoboken, 2008. Peter Kall and Stein W. Wallace, Stochastic Programming, John Wiley & Sons, Chichester, 1994. Rhodes, D.H., Lamb

Beatrix Potter: Seeing Beauty in the Simplest Things.

ERIC Educational Resources Information Center

Brodie, Carolyn S.

2002-01-01

Discusses the life and works of Beatrix Potter. Suggests ideas for related extension activities and provides an annotated bibliography, including books in the Peter Rabbit series; selected publications based on the Peter Rabbit series; Web resources; books about Beatrix Potter; and additional print resources. (LRW)

Iran’s Nuclear Program: An Assessment of the Threat to the United States

DTIC Science & Technology

2009-12-01

Mohammad Reza Pahlavi. Peter Haggett, Encyclopedia of World Geography, Volume 15 (Oxfordshire: Andromeda Oxford, 2002), 2,044. 16...Peter. Encyclopedia of World Geography, Volume 15. Oxfordshire: Andromeda Oxford, 2002. Hersh, Seymour. The Samson Option: Israel’s Nuclear Arsenal

Operational Art in Cyber Defense

DTIC Science & Technology

2013-04-16

a personal curiosity. I used the masculine when referring to the Commander and the adversary throughout this paper for brevity. Alanis 1...issue 63, (4th quarter 2011): 70-73. 13 Carl von Clausewitz, On War, ed. Michael Howard and Peter Paret, trans . Michael Howard and Peter Paret

Peter Waterman and T-Matrix Methods

NASA Technical Reports Server (NTRS)

Mishchenko, M. I.; Martin, P.A.

2013-01-01

This paper summarizes the scientific legacy of Peter C. Waterman (1928-2012) who introduced concepts and theoretical techniques that have had a major impact on the fields of scattering by particles and particle groups, optical particletcharacterization, radiative transfer, and remote sensing. A biographical sketch is also included.

Respect in Education

ERIC Educational Resources Information Center

Giesinger, Johannes

2012-01-01

This article discusses the educational significance of the moral demand for respect. In "Ethics and Education," Richard Peters presents a conception of educational respect that was recently taken up by Krassimir Stojanov. This article responds to both Peters' and Stojanov's contributions and proposes another understanding of educational respect:…

Peter Jarvis and the Understanding of Adult Learning

ERIC Educational Resources Information Center

Illeris, Knud

2017-01-01

By comparing Peter Jarvis' understanding of learning with two other approaches--which Jarvis himself has referred to as "the most comprehensive": Etienne Wenger's "social theory of learning" and my own psychologically oriented theory of "the three dimensions of learning"--it becomes evident that Jarvis' understanding…

ARC-2009-ACD09-0108-037

NASA Image and Video Library

2009-02-08

An SUV-sized Asteroid 2008TC# Impacts on October 7, 2008 in the Nubian Desert, Northern Sudan: Dr. Peter Jenniskens, NASA/SETI joined Muawia Shaddas of the University of Khartoum in leading an expedition on a search for samples. Peter Jenniskens Photo Credit: NASA/SETI/P. Jenniskens

Superfund Record of Decision (EPA Region 5): Reilly Tar and Chemical Corporation Site, St. Peter Aquifer, St. Louis Park, MN. (Third remedial action), September 1990

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-09-28

The 80-acre Reilly Tar and Chemical (St. Louis Park) site is a former coal tar distillation and wood preserving plant in St. Louis Park, Minnesota. The site overlies a complex system of aquifers, including the St. Peter aquifer that provide drinking water to area residences. The St. Peter Aquifer contains one municipal well, which is used during periods of peak demand, however, the majority of the drinking water in St. Louis Park is obtained from deeper aquifers. From 1917 to 1972, wastewater containing creosote and coal tar was discharged to onsite surface water, and as a result, small wastewater spillsmore » occurred into onsite soil. The ROD addresses Operable Unit 4 (OU4), remediation of the St. Peter aquifer. A subsequent ROD will address any remaining site problems as OU3. The primary contaminants of concern affecting the ground water are organics including PAHs and phenols.« less

Reflections on the nature of non-linear responses of the climate to forcing

NASA Astrophysics Data System (ADS)

Ditlevsen, Peter

2017-04-01

On centennial to multi-millennial time scales the paleoclimatic record shows that climate responds in a very non-linear way to the external forcing. Perhaps most puzzling is the change in glacial period duration at the Middle Pleistocene Transition. From a dynamical systems perspective, this could be a change in frequency locking between the orbital forcing and the climatic response or it could be a non-linear resonance phenomenon. In both cases the climate system shows a non-trivial oscillatory behaviour. From the records it seems that this behaviour can be described by an effective dynamics on a low-dimensional slow manifold. These different possible dynamical behaviours will be discussed. References: Arianna Marchionne, Peter Ditlevsen, and Sebastian Wieczorek, "Three types of nonlinear resonances", arXiv:1605.00858 Peter Ashwin and Peter Ditlevsen, "The middle Pleistocene transition as a generic bifurcation on a slow manifold", Climate Dynamics, 45, 2683, 2015. Peter D. Ditlevsen, "The bifurcation structure and noise assisted transitions in the Pleistocene glacial cycles", Paleoceanography, 24, PA3204, 2009

HOx Observation and Model Comparison During INTEX-A 2004

NASA Technical Reports Server (NTRS)

Ren, Xinrong; Olson, Jennifer R.; Crawford, James H.; Brune, William H.; Mao, Jingqiu; Long, Robert B.; Chen, Zhong; Chen, Gao; Avery, Melody A.; Sachse, Glen W.;

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 3 2012-07-01 2012-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

Academic Degradation and the Retreat of the Editors: Academic Irregularities and the Spreading of Academic Corruption from an Editor's Perspective

ERIC Educational Resources Information Center

Xun, Gong

2007-01-01

Against the backdrop of the grave academic crisis in China, editors have become the objects of wooing, favor-currying, connections-seeking, and collusions; they have been targeted for attacks, plots, extortions, and encroachments. Editing and publishing have become avenues for academic irregularities and academic corruption. Editors have the power…

Heme Oxygenase Inhibition Sensitizes Neuroblastoma Cells to Carfilzomib.

PubMed

Barbagallo, Ignazio; Giallongo, Cesarina; Volti, Giovanni Li; Distefano, Alfio; Camiolo, Giuseppina; Raffaele, Marco; Salerno, Loredana; Pittalà, Valeria; Sorrenti, Valeria; Avola, Roberto; Di Rosa, Michelino; Vanella, Luca; Di Raimondo, Francesco; Tibullo, Daniele

2018-06-10

Neuroblastoma (NB) is an embryonic malignancy affecting the physiological development of adrenal medulla and paravertebral sympathetic ganglia in early infancy. Proteasome inhibitors (PIs) (i.e., carfilzomib (CFZ)) may represent a possible pharmacological treatment for solid tumors including NB. In the present study, we tested the effect of a novel non-competitive inhibitor of heme oxygenase-1 (HO-1), LS1/71, as a possible adjuvant therapy for the efficacy of CFZ in neuroblastoma cells. Our results showed that CFZ increased both HO-1 gene expression (about 18-fold) and HO activity (about 8-fold), following activation of the ER stress pathway. The involvement of HO-1 in CFZ-mediated cytotoxicity was further confirmed by the protective effect of pharmacological induction of HO-1, significantly attenuating cytotoxicity. In addition, HO-1 selective inhibition by a specific siRNA increased the cytotoxic effect following CFZ treatment in NB whereas SnMP, a competitive pharmacological inhibitor of HO, showed no changes in cytotoxicity. Our data suggest that treatment with CFZ produces ER stress in NB without activation of CHOP-mediated apoptosis, whereas co-treatment with CFZ and LS1/71 led to apoptosis activation and CHOP expression induction. In conclusion, our study showed that treatment with the non-competitive inhibitor of HO-1, LS1 / 71, increased cytotoxicity mediated by CFZ, triggering apoptosis following ER stress activation. These results suggest that PIs may represent a possible pharmacological treatment for solid tumors and that HO-1 inhibition may represent a possible strategy to overcome chemoresistance and increase the efficacy of chemotherapic regimens.

High oleic ready-to-use therapeutic food maintains docosahexaenoic acid status in severe malnutrition: a randomized, blinded trial

PubMed Central

Hsieh, Ji-Cheng; Liu, Lei; Zeilani, Mamane; Ickes, Scott; Trehan, Indi; Maleta, Ken; Craig, Christina; Thakwalakwa, Chrissie; Singh, Lauren; Brenna, J. Thomas; Manary, Mark J.

2015-01-01

Objective Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. RUTF contains large amounts of linoleic acid and very little α-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status. Methods We conducted a prospective, randomized, double-blinded, clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid (PL) fatty acid status was measured upon enrollment and after 4 weeks and compared between the two intervention groups. Results Among the 141 children enrolled, 48/71 receiving HO-RUTF and 50/70 receiving RUTF recovered. Plasma PL samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and −25% in the HO-RUTF and RUTF groups, respectively (P = 0.04). For EPA, the change in content was 63% and −24% in the HO-RUTF and RUTF groups (P < 0.001). For arachidonic acid, the change in content was −3% and 13% in the HO-RUTF and RUTF groups (P < 0.009). Conclusions The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation as they suggest HO-RUTF support improved PUFA status, necessary for neural development and recovery. PMID:25633498

Solution 1H NMR investigation of the active site molecular and electronic structures of substrate-bound, cyanide-inhibited HmuO, a bacterial heme oxygenase from Corynebacterium diphtheriae.

PubMed

Li, Yiming; Syvitski, Ray T; Chu, Grace C; Ikeda-Saito, Masao; Mar, Gerd N La

2003-02-28

The molecular structure and dynamic properties of the active site environment of HmuO, a heme oxygenase (HO) from the pathogenic bacterium Corynebacterium diphtheriae, have been investigated by (1)H NMR spectroscopy using the human HO (hHO) complex as a homology model. It is demonstrated that not only the spatial contacts among residues and between residues and heme, but the magnetic axes that can be related to the direction and magnitude of the steric tilt of the FeCN unit are strongly conserved in the two HO complexes. The results indicate that very similar contributions of steric blockage of several meso positions and steric tilt of the attacking ligand are operative. A distal H-bond network that involves numerous very strong H-bonds and immobilized water molecules is identified in HmuO that is analogous to that previously identified in hHO (Li, Y., Syvitski, R. T., Auclair, K., Wilks, A., Ortiz de Montellano, P. R., and La Mar, G. N. (2002) J. Biol. Chem. 277, 33018-33031). The NMR results are completely consistent with the very recent crystal structure of the HmuO.substrate complex. The H-bond network/ordered water molecules are proposed to orient the distal water molecule near the catalytically key Asp(136) (Asp(140) in hHO) that stabilizes the hydroperoxy intermediate. The dynamic stability of this H-bond network in HmuO is significantly greater than in hHO and may account for the slower catalytic rate in bacterial HO compared with mammalian HO.

Role of the heme oxygenases in abnormalities of the mesenteric circulation in cirrhotic rats.

PubMed

Sacerdoti, David; Abraham, Nader G; Oyekan, Adebayo O; Yang, Liming; Gatta, Angelo; McGiff, John C

2004-02-01

Carbon monoxide (CO), a product of heme metabolism by heme-oxygenase (HO), has biological actions similar to those of nitric oxide (NO). The role of CO in decreasing vascular responses to constrictor agents produced by experimental cirrhosis induced by carbon tetrachloride was evaluated before and after inhibition of HO with tin-mesoporphyrin (SnMP) in the perfused superior mesenteric vasculature (SMV) of cirrhotic and normal rats and in normal rats transfected with the human HO-1 (HHO-1) gene. Perfusion pressure and vasoconstrictor responses of the SMV to KCl, phenylephrine (PE), and endothelin-1 (ET-1) were decreased in cirrhotic rats. SnMP increased SMV perfusion pressure and restored the constrictor responses of the SMV to KCl, PE, and ET-1 in cirrhotic rats. The relative roles of NO and CO in producing hyporeactivity of the SMV to PE in cirrhotic rats were examined. Vasoconstrictor responses to PE were successively augmented by stepwise inhibition of CO and NO production, suggesting a complementary role for these gases in the regulation of reactivity of the SMV. Expression of constitutive but not of inducible HO (HO-1) was increased in the SMV of cirrhotic rats as was HO activity. Administration of adenovirus containing HHO-1 gene produced detection of HHO-1 RNA and increased HO activity in the SMV within 7 days. Rats transfected with HO-1 demonstrated reduction in both perfusion pressure and vasoconstrictor responses to PE in the SMV. We propose that HO is an essential component in mechanisms that modulate reactivity of the mesenteric circulation in experimental hepatic cirrhosis in rats.

Functional imaging: monitoring heme oxygenase-1 gene expression in vivo

NASA Astrophysics Data System (ADS)

Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

1999-07-01

The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

Adverse effect on syngeneic islet transplantation by transgenic coexpression of decoy receptor 3 and heme oxygenase-1 in the islet of NOD mice.

PubMed

Huang, S-H; Lin, G-J; Chien, M-W; Chu, C-H; Yu, J-C; Chen, T-W; Hueng, D-Y; Liu, Y-L; Sytwu, H-K

2013-03-01

Decoy receptor 3 (DcR3) blocks both Fas ligand- and LIGHT-induced pancreatic β-cell damage in autoimmune diabetes. Heme oxygenase 1 (HO-1) possesses antiapoptotic, anti-inflammatory, and antioxidative effects that protect cells against various forms of attack by the immune system. Previously, we have demonstrated that transgenic islets overexpressing DcR3 or murine HO-1 (mHO-1) exhibit longer survival times than nontransgenic islets in syngeneic islet transplantation. In this study, we evaluated whether DcR3 and mHO-1 double-transgenic islets of NOD mice could provide better protective effects and achieve longer islet graft survival than DcR3 or mHO-1 single-transgenic islets after islet transplantation. We generated DcR3 and mHO-1 double-transgenic NOD mice that specifically overexpress DcR3 and HO-1 in islets. Seven hundred islets isolated from double-transgenic, single-transgenic, or nontransgenic NOD mice were syngeneically transplanted into the kidney capsules of newly diabetic female recipients. Unexpectedly, there was no significant difference in the survival time between double-transgenic or nontransgenic NOD islet grafts, and the survival times of double-transgenic NOD islet grafts were even shorter than those of DcR3 or mHO-1 single-transgenic islets. Our data indicate that transplantation of double-transgenic islets that coexpress HO-1 and DcR3 did not result in a better outcome. On the contrary, this strategy even caused an adverse effect in syngeneic islet transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakao, Atsunori; Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Kaczorowski, David J.

2008-03-14

Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H{sub 2}O{sub 2}-induced cell death of mvECs in association with HO-1 induction. Thesemore » protective effects were completely reversed by nuclear factor-{kappa}B (NF-{kappa}B) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-{kappa}B activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease.« less

Norharmane rhenium(I) polypyridyl complexes: synthesis, structural and spectroscopic characterization.

PubMed

Maisuls, Iván; Wolcan, Ezequiel; Piro, Oscar E; Etcheverría, Gustavo A; Petroselli, Gabriela; Erra-Ballsels, Rosa; Cabrerizo, Franco M; Ruiz, Gustavo T

2015-10-21

Two novel Re(i) complexes with the general formula fac-[Re(CO)3(L)(nHo)]CF3SO3, where L = 2,2'-bipyridine (bpy) or 1,10 phenanthroline (phen) and nHo (9H-pyrido[3,4-b]indole; norharmane) have been synthesized. The Re(i)-nHo complexes were characterized by structural X-ray diffraction, (1)H and (13)C NMR, UV-vis absorption and FT-IR spectroscopy, and by a combination of two mass spectrometry techniques, namely ESI-MS and UV-MALDI-MS. All characterizations showed that nHo is coordinated to the metal atom by the pyridine nitrogen of the molecule. X-ray structural analysis revealed that the crystal lattices for both complexes are further stabilized by a strong >N-HO bond between the pyrrole NH group of the pyridoindole ligand and one oxygen atom of the trifluoromethanesulfonate counter-ion. Ground state geometry optimization by DFT calculations showed that in fluid solution the nHo ligand may rotate freely. The nature of the electronic transitions of Re(CO)3(bpy)(nHo)(+) were established by TD-DFT calculations. The set of the most important electronic transitions present in this complex are comprised of π→π* electronic transitions centered on bpy and nHo moieties, LLCTnHo→COs, MLLCTRe(CO)3→bpy and LLCTnHo→bpy transitions. Additionally, TD-DFT calculations predict the existence of another two intense MLLCTRe(CO)3→nHo electronic transitions. Calculated UV-vis absorption spectra are in good agreement with the corresponding experimental data for the bpy-containing complex.

Development of flashlamp-pumped Q-switched Ho:Tm:Cr:YAG lasers for mid-infrared LIDAR application

NASA Technical Reports Server (NTRS)

Choi, Young S.; Kim, Kyong H.; Whitney, Donald A.; Hess, Robert V.; Barnes, Norman P.; Bair, Clayton H.; Brockman, Philip

1989-01-01

A flashlamp-pumped 2.1 micron Ho:Tm:Cr:YAG laser was studied for both normal mode and Q-switched operations under a wide variety of experimental conditions in order to optimize performance. Laser output energy, slope efficiency, threshold and pulselength were determined as a function of operating temperature, output mirror reflectivity, input electrical energy and Q-switch opening time. The measured normal-mode laser thresholds of a Ho(3+) (0.45 atomic percent):Tm(3+) (2.5 atomic percent):Cr(3+) (0.8 atomic percent):YAG crystal ranged form 26 to 50 J between 120 and 200 K with slope efficiencies up to 0.36 percent with a 60 percent reflective output mirror. Under Q-switched operation the slope efficiency was 90 percent of the normal-mode result. Development of solid state lasers with Ho(3+), Tm(3+) and/or Er(3+) doped crystals has been pursued by NASA for eye-dafe mid-infrared LIDAR (light detection and ranging) application. As a part of the project, the authors have been working on evaluating Ho(3+):Tm(3+):Cr(3+):YAG crystals for normal-mode and Q-switched 2.1 micron laser operations in order to determine an optimum Tm(3+) concentration under flashlamp pumping conditions. Lasing properties of the Ho(3+) in the mid-infrared region have been studied by many research groups since the early 1960's. However, the technology of those lasers is still premature for lidar application. In order to overcome the inefficiency related to narrow absorption bands of the Ho(3+), Tm(3+) and Er(3+), the erbium has been replaced by chromium. The improvement in flashlamp-pumped Ho(3+) laser efficiency has been demonstrated recently by several research groups by utilizing the broad absorption spectrum of Cr(3+) which covers the flashlamp's emission spectrum. Efficient energy transfer to the Tm(3+) and then the Ho(3+) occurs subsequently. It is known that high Tm(3+) concentration and low Ho(3+) concentration are preferred to achieve a quantum efficiency approaching two and to avoid large reabsorption losses. However, determination of the optimum Tm(3+) concentration required to ensure efficient energy transfer from Cr(3+) to Tm(3+) and from Tm(3+) to Ho(3+) has not been made in the Ho:Tm:CR:YAG crystal. The results obtained so far are given.

Transgenic expression of human heme oxygenase-1 in pigs confers resistance against xenograft rejection during ex vivo perfusion of porcine kidneys.

PubMed

Petersen, Björn; Ramackers, Wolf; Lucas-Hahn, Andrea; Lemme, Erika; Hassel, Petra; Queisser, Anna-Lisa; Herrmann, Doris; Barg-Kues, Brigitte; Carnwath, Joseph W; Klose, Johannes; Tiede, Andreas; Friedrich, Lars; Baars, Wiebke; Schwinzer, Reinhard; Winkler, Michael; Niemann, Heiner

2011-01-01

The major immunological hurdle to successful porcine-to-human xenotransplantation is the acute vascular rejection (AVR), characterized by endothelial cell (EC) activation and perturbation of coagulation. Heme oxygenase-1 (HO-1) and its derivatives have anti-apoptotic, anti-inflammatory effects and protect against reactive oxygen species, rendering HO-1 a promising molecule to control AVR. Here, we report the production and characterization of pigs transgenic for human heme oxygenase-1 (hHO-1) and demonstrate significant protection in porcine kidneys against xenograft rejection in ex vivo perfusion with human blood and transgenic porcine aortic endothelial cells (PAEC) in a TNF-α-mediated apoptosis assay. Transgenic and non-transgenic PAEC were tested in a TNF-α-mediated apoptosis assay. Expression of adhesion molecules (ICAM-1, VCAM-1, and E-selectin) was measured by real-time PCR. hHO-1 transgenic porcine kidneys were perfused with pooled and diluted human AB blood in an ex vivo perfusion circuit. MHC class-II up-regulation after induction with IFN-γ was compared between wild-type and hHO-1 transgenic PAEC. Cloned hHO-1 transgenic pigs expressed hHO-1 in heart, kidney, liver, and in cultured ECs and fibroblasts. hHO-1 transgenic PAEC were protected against TNF-α-mediated apoptosis. Real-time PCR revealed reduced expression of adhesion molecules like ICAM-1, VCAM-1, and E-selectin. These effects could be abrogated by the incubation of transgenic PAECs with the specific HO-1 inhibitor zinc protoporphorine IX (Zn(II)PPIX, 20 μm). IFN-γ induced up-regulation of MHC class-II molecules was significantly reduced in PAECs from hHO-1 transgenic pigs. hHO-1 transgenic porcine kidneys could successfully be perfused with diluted human AB-pooled blood for a maximum of 240 min (with and without C1 inh), while in wild-type kidneys, blood flow ceased after ∼60 min. Elevated levels of d-Dimer and TAT were detected, but no significant consumption of fibrinogen and antithrombin was determined. Microthrombi could not be detected histologically. These results are encouraging and warrant further studies on the biological function of heme oxygenase-I expression in hHO-1 transgenic pigs in the context of xenotransplantation. © 2011 John Wiley & Sons A/S.

Heme oxygenase-1 system and gastrointestinal tumors

PubMed Central

Zhu, Xiao; Fan, Wen-Guo; Li, Dong-Pei; Lin, Marie CM; Kung, Hsiangfu

2010-01-01

Heme oxygenase-1 (HO-1) system catabolizes heme into three products: carbon monoxide, biliverdin/bilirubin and free iron. It is involved in many physiological and pathophysiological processes. A great deal of data has demonstrated the roles of HO-1 in the formation, growth and metastasis of tumors. The interest in this system by investigators involved in gastrointestinal tumors is fairly recent, and few papers on HO-1 have touched upon this subject. This review focuses on the current understanding of the physiological significance of HO-1 induction and its possible roles in the gastrointestinal tumors studied to date. The implications for possible therapeutic manipulation of HO-1 in gastrointestinal tumors are also discussed. PMID:20518085

Anisotropic magnetocaloric effect in HoAlGa polycrystalline compound

NASA Astrophysics Data System (ADS)

Yan, Zhang; Xinqi, Zheng; JieFu, Xiong; Shulan, Zuo; Qiaoyan, Dong; Tongyun, Zhao; Baogen, Shen

2018-05-01

In this work, a nonnegligible anisotropic magnetocaloric effect (MCE) in HoAlGa polycrystalline compounds has been observed. With temperature increasing, the HoAlGa compound undergoes two kinds of magnetic transitions at 19 K and 31 K, respectively, the later has been recognized as an ordinary antiferromagnetic to paramagnetic (AFM-PM) transition. The -ΔS peak of HoAGa reaches 5.4 J/kg K and 1.5 J/kg K at 35 K along parallel and perpendicular texture directions respectively, for a field change of 0-5 T. The result indicates that the HoAlGa polycrystalline compounds with excellent anisotropic MCE can be expected to have effective magnetic refrigeration applications in low temperature range.

Reliability and Validity of the HoNOS-LD and HoNOS in a Sample of Individuals with Mild to Borderline Intellectual Disability and Severe Emotional and Behavior Disorders

ERIC Educational Resources Information Center

Tenneij, Nienke; Didden, Robert; Veltkamp, Eline; Koot, Hans M.

2009-01-01

In this study, psychometric properties of the Health of the Nation Outcome scales (HoNOS) and Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) were investigated in a sample (n = 79) of (young) adults with mild to borderline intellectual disability (ID) and severe behavior and mental health problems who were…

Early Diagnosis and Intervention Strategies for Post-Traumatic Heterotopic Ossification in Severely Injured Extremities

DTIC Science & Technology

2013-10-01

study will recruit wounded warriors with severe extremity trauma, which places them at high risk for heterotopic ossification (HO); bone formation at...involved in HO; 2) to define accurate and practical methods to predict where HO will develop; and 3) to define potential therapies for prevention or...elicit HO. These tools also need to provide effective methods for early diagnosis or risk assessment (prediction) so that therapies for prevention or

High-power and highly efficient diode-cladding-pumped Ho3+-doped silica fiber lasers.

PubMed

Jackson, Stuart D; Bugge, Frank; Erbert, Götz

2007-11-15

We demonstrate high-power operation from a singly Ho3+-doped silica fiber laser that is cladding pumped directly with diode lasers operating at 1150 nm. Internal slope efficiencies approaching the Stokes limit were produced, and the maximum output power was 2.2W. This result was achieved using a low Ho3+-ion concentration and La3+-ion codoping, which together limit the transfer of energy between excited Ho3+ ions.

Heme oxygenase 1 defects lead to reduced chlorophyll in Brassica napus.

PubMed

Zhu, Lixia; Yang, Zonghui; Zeng, Xinhua; Gao, Jie; Liu, Jie; Yi, Bin; Ma, Chaozhi; Shen, Jinxiong; Tu, Jinxing; Fu, Tingdong; Wen, Jing

2017-04-01

We previously described a Brassica napus chlorophyll-deficient mutant (ygl) with yellow-green seedling leaves and mapped the related gene, BnaC.YGL, to a 0.35 cM region. However, the molecular mechanisms involved in this chlorophyll defect are still unknown. In this study, the BnaC07.HO1 gene (equivalent to BnaC.YGL) was isolated by the candidate gene approach, and its function was confirmed by genetic complementation. Comparative sequencing analysis suggested that BnaC07.HO1 was lost in the mutant, while a long noncoding-RNA was inserted into the promoter of the homologous gene BnaA07.HO1. This insert was widely present in B. napus cultivars and down-regulated BnaA07.HO1 expression. BnaC07.HO1 was highly expressed in the seedling leaves and encoded heme oxygenase 1, which was localized in the chloroplast. Biochemical analysis showed that BnaC07.HO1 can catalyze heme conversion to form biliverdin IXα. RNA-seq analysis revealed that the loss of BnaC07.HO1 impaired tetrapyrrole metabolism, especially chlorophyll biosynthesis. According, the levels of chlorophyll intermediates were reduced in the ygl mutant. In addition, gene expression in multiple pathways was affected in ygl. These findings provide molecular evidences for the basis of the yellow-green leaf phenotype and further insights into the crucial role of HO1 in B. napus.

Vasculoprotective effects of heme oxygenase-1 in a murine model of hyperoxia-induced bronchopulmonary dysplasia

PubMed Central

Fernandez-Gonzalez, Angeles; Alex Mitsialis, S.; Liu, Xianlan

2012-01-01

Bronchopulmonary dysplasia (BPD) is characterized by simplified alveolarization and arrested vascular development of the lung with associated evidence of endothelial dysfunction, inflammation, increased oxidative damage, and iron deposition. Heme oxygenase-1 (HO-1) has been reported to be protective in the pathogenesis of diseases of inflammatory and oxidative etiology. Because HO-1 is involved in the response to oxidative stress produced by hyperoxia and is critical for cellular heme and iron homeostasis, it could play a protective role in BPD. Therefore, we investigated the effect of HO-1 in hyperoxia-induced lung injury using a neonatal transgenic mouse model with constitutive lung-specific HO-1 overexpression. Hyperoxia triggered an increase in pulmonary inflammation, arterial remodeling, and right ventricular hypertrophy that was attenuated by HO-1 overexpression. In addition, hyperoxia led to pulmonary edema, hemosiderosis, and a decrease in blood vessel number, all of which were markedly improved in HO-1 overexpressing mice. The protective vascular response may be mediated at least in part by carbon monoxide, due to its anti-inflammatory, antiproliferative, and antiapoptotic properties. HO-1 overexpression, however, did not prevent alveolar simplification nor altered the levels of ferritin and lactoferrin, proteins involved in iron binding and transport. Thus the protective mechanisms elicited by HO-1 overexpression primarily preserve vascular growth and barrier function through iron-independent, antioxidant, and anti-inflammatory pathways. PMID:22287607

In vivo regulation of the heme oxygenase-1 gene in humanized transgenic mice

PubMed Central

Kim, Junghyun; Zarjou, Abolfazl; Traylor, Amie M.; Bolisetty, Subhashini; Jaimes, Edgar A.; Hull, Travis D.; George, James F.; Mikhail, Fady M.; Agarwal, Anupam

2012-01-01

Heme oxygenase-1 (HO-1) catalyzes the rate-limiting step in heme degradation producing equimolar amounts of carbon monoxide, iron, and biliverdin. Induction of HO-1 is a beneficial response to tissue injury in diverse animal models of diseases including acute kidney injury. In vitro analysis has shown that the human HO-1 gene is transcriptionally regulated by changes in chromatin conformation but whether such control occurs in vivo is not known. To enable such analysis, we generated transgenic mice, harboring an 87-kb bacterial artificial chromosome expressing human HO-1 mRNA and protein and bred these mice with HO-1 knockout mice to generate humanized BAC transgenic mice. This successfully rescued the phenotype of the knockout mice including reduced birth rates, tissue iron overload, splenomegaly, anemia, leukocytosis, dendritic cell abnormalities and survival after acute kidney injury induced by rhabdomyolysis or cisplatin nephrotoxicity. Transcription factors such as USF1/2, JunB, Sp1, and CTCF were found to associate with regulatory regions of the human HO-1 gene in the kidney following rhabdomyolysis. Chromosome Conformation Capture and ChIP-loop assays confirmed this in the formation of chromatin looping in vivo. Thus, these bacterial artificial chromosome humanized HO-1 mice are a valuable model to study the human HO-1 gene providing insight to the in vivo architecture of the gene in acute kidney injury and other diseases. PMID:22495295

High-pulse-energy 3.9-μm lasers in Ho:BYF

NASA Astrophysics Data System (ADS)

Stutz, Russell; Miller, Harold C.; Dinndorf, Kenneth M.; Cassanho, Arlete; Jenssen, Hans P.

2004-07-01

Experimental results describing pulsed lasers operating near 3.9 μm on the Ho3+ (5I5-5I6) transition in highly-doped (> 10 at. %) barium yttrium fluoride (BaY2F8 or BYF) will be presented. The 5I5 manifolds in Ho:BYF were pumped using a flashlamp excited, free-running Cr:LiSAF laser tuned to the Ho3+ absorption peak near 889nm. Ho3+ concentrations of 10%, 20%, 30% and 40% in BYF were lased in a simple end-pumped resonator. Some similar data was also obtained in 10% and 20% Ho:YLF. The highest 3.9 μm pulse energy obtained in the comparative study was 55 mJ (at ~10% optical-to-optical efficiency) using the 30% Ho:BYF crystal. A dual end-pumped laser in 30% Ho:BYF was also demonstrated, providing a pulse energy of 90 mJ in a near diffraction limited beam (M2 ~ 1.2). Emission decay data was taken to shed light on the observed dependence of laser efficiency on holmium concentration and excitation density. The lifetimes of both lasing levels (5I5 and 5I6) deviate rather significantly from their low-concentration values. Plausible energy transfer processes that may be responsible for the observed trends in the laser and emission data will also be discussed.

Mica Nanoparticle, STB-HO Eliminates the Human Breast Carcinoma Cells by Regulating the Interaction of Tumor with its Immune Microenvironment.

PubMed

Kang, Tae-Wook; Kim, Hyung-Sik; Lee, Byung-Chul; Shin, Tae-Hoon; Choi, Soon Won; Kim, Yoon-Jin; Lee, Hwa-Yong; Jung, Yeon-Kwon; Seo, Kwang-Won; Kang, Kyung-Sun

2015-12-03

Mica, an aluminosilicate mineral, has been proven to possess anti-tumor and immunostimulatory effects. However, its efficacy and mechanisms in treating various types of tumor are less verified and the mechanistic link between anti-tumor and immunostimulatory effects has not been elucidated. We sought to investigate the therapeutic effect of STB-HO (mica nanoparticles) against one of the most prevalent cancers, the breast cancer. STB-HO was orally administered into MCF-7 xenograft model or directly added to culture media and tumor growth was monitored. STB-HO administration exhibited significant suppressive effects on the growth of MCF-7 cells in vivo, whereas STB-HO did not affect the proliferation and apoptosis of MCF-7 cells in vitro. To address this discrepancy between in vivo and in vitro results, we investigated the effects of STB-HO treatment on the interaction of MCF-7 cells with macrophages, dendritic cells (DCs) and natural killer (NK) cells, which constitute the cellular composition of tumor microenvironment. Importantly, STB-HO not only increased the susceptibility of MCF-7 cells to immune cells, but also stimulated the immunocytes to eliminate cancer cells. In conclusion, our study highlights the possible role of STB-HO in the suppression of MCF-7 cell growth via the regulation of interactions between tumor cells and anti-tumor immune cells.

Mica Nanoparticle, STB-HO Eliminates the Human Breast Carcinoma Cells by Regulating the Interaction of Tumor with its Immune Microenvironment

PubMed Central

Kang, Tae-Wook; Kim, Hyung-Sik; Lee, Byung-Chul; Shin, Tae-Hoon; Choi, Soon Won; Kim, Yoon-Jin; Lee, Hwa-Yong; Jung, Yeon-Kwon; Seo, Kwang-Won; Kang, Kyung-Sun

2015-01-01

Mica, an aluminosilicate mineral, has been proven to possess anti-tumor and immunostimulatory effects. However, its efficacy and mechanisms in treating various types of tumor are less verified and the mechanistic link between anti-tumor and immunostimulatory effects has not been elucidated. We sought to investigate the therapeutic effect of STB-HO (mica nanoparticles) against one of the most prevalent cancers, the breast cancer. STB-HO was orally administered into MCF-7 xenograft model or directly added to culture media and tumor growth was monitored. STB-HO administration exhibited significant suppressive effects on the growth of MCF-7 cells in vivo, whereas STB-HO did not affect the proliferation and apoptosis of MCF-7 cells in vitro. To address this discrepancy between in vivo and in vitro results, we investigated the effects of STB-HO treatment on the interaction of MCF-7 cells with macrophages, dendritic cells (DCs) and natural killer (NK) cells, which constitute the cellular composition of tumor microenvironment. Importantly, STB-HO not only increased the susceptibility of MCF-7 cells to immune cells, but also stimulated the immunocytes to eliminate cancer cells. In conclusion, our study highlights the possible role of STB-HO in the suppression of MCF-7 cell growth via the regulation of interactions between tumor cells and anti-tumor immune cells. PMID:26631982

Hemeoxygenase-1 Mediates an Adaptive Response to Spermidine-Induced Cell Death in Human Endothelial Cells

PubMed Central

Yang, Hana; Lee, Seung Eun; Kim, Gun-Dong; Park, Hye Rim; Park, Yong Seek

2013-01-01

Spermidine (SPD) is a ubiquitous polycation that is commonly distributed in living organisms. Intracellular levels of SPD are tightly regulated, and SPD controls cell proliferation and death. However, SPD undergoes oxidation in the presence of serum, producing aldehydes, hydrogen peroxide, and ammonia, which exert cytotoxic effect on cells. Hemeoxygenase-1 (HO-1) is thought to have a protective effect against oxidative stress. Upregulation of HO-1 in endothelial cells is considered to be beneficial in the cardiovascular disease. In the present study, we demonstrate that the ubiquitous polyamine, SPD, induces HO-1 in human umbilical vein endothelial cells (HUVECs). SPD-induced HO-1 expression was examined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Involvement of reactive oxygen species, serum amine oxidase, PI3K/Akt signaling pathway, and transcription factor Nrf2 in the induction of HO-1 by SPD was also investigated. Furthermore, small interfering RNA knockdown of Nrf2 or HO-1 and treatment with the specific HO-1 inhibitor ZnPP exhibited a noteworthy increase of death of SPD-stimulated HUVECs. In conclusion, these results suggest that SPD induces PI3K/Akt-Nrf2-mediated HO-1 expression in human endothelial cells, which may have a role in cytoprotection of the cells against oxidative stress-induced death. PMID:23983896

Vibrational non-equilibrium in the hydrogen-oxygen reaction. Comparison with experiment

NASA Astrophysics Data System (ADS)

Skrebkov, Oleg V.

2015-03-01

A theoretical model is proposed for the chemical and vibrational kinetics of hydrogen oxidation based on consistent accounting of the vibrational non-equilibrium of the HO2 radical that forms as a result of the bimolecular recombination H+O2 → HO2. In the proposed model, the chain branching H+O2 = O+OH and inhibiting H+O2+M = HO2+M formal reactions are treated (in the terms of elementary processes) as a single multi-channel process of forming, intramolecular energy redistribution between modes, relaxation, and unimolecular decay of the comparatively long-lived vibrationally excited HO2 radical, which is able to react and exchange energy with the other components of the mixture. The model takes into account the vibrational non-equilibrium of the starting (primary) H2 and O2 molecules, as well as the most important molecular intermediates HO2, OH, O2(1Δ), and the main reaction product H2O. It is shown that the hydrogen-oxygen reaction proceeds in the absence of vibrational equilibrium, and the vibrationally excited HO2(v) radical acts as a key intermediate in a fundamentally important chain branching process and in the generation of electronically excited species O2(1Δ), O(1D), and OH(2Σ+). The calculated results are compared with the shock tube experimental data for strongly diluted H2-O2 mixtures at 1000 < T < 2500 K, 0.5 < p < 4 atm. It is demonstrated that this approach is promising from the standpoint of reconciling the predictions of the theoretical model with experimental data obtained by different authors for various compositions and conditions using different methods. For T < 1500 K, the nature of the hydrogen-oxygen reaction is especially non-equilibrium, and the vibrational non-equilibrium of the HO2 radical is the essence of this process. The quantitative estimation of the vibrational relaxation characteristic time of the HO2 radical in its collisions with H2 molecules has been obtained as a result of the comparison of different experimental data on induction time measurements with the relevant calculations.

Expression and characterization of full-length human heme oxygenase-1: the presence of intact membrane-binding region leads to increased binding affinity for NADPH cytochrome P450 reductase.

PubMed

Huber, Warren J; Backes, Wayne L

2007-10-30

Heme oxygenase-1 (HO-1) is the chief regulatory enzyme in the oxidative degradation of heme to biliverdin. In the process of heme degradation, HO-1 receives the electrons necessary for catalysis from the flavoprotein NADPH cytochrome P450 reductase (CPR), releasing free iron and carbon monoxide. Much of the recent research involving heme oxygenase has been done using a 30 kDa soluble form of the enzyme, which lacks the membrane binding region (C-terminal 23 amino acids). The goal of this study was to express and purify a full-length human HO-1 (hHO-1) protein; however, due to the lability of the full-length form, a rapid purification procedure was required. This was accomplished by use of a glutathione-s-transferase (GST)-tagged hHO-1 construct. Although the procedure permitted the generation of a full-length HO-1, this form was contaminated with a 30 kDa degradation product that could not be eliminated. Therefore, attempts were made to remove a putative secondary thrombin cleavage site by a conservative mutation of amino acid 254, which replaces arginine with lysine. This mutation allowed the expression and purification of a full-length hHO-1 protein. Unlike wild type (WT) HO-1, the R254K mutant could be purified to a single 32 kDa protein capable of degrading heme at the same rate as the WT enzyme. The R254K full-length form had a specific activity of approximately 200-225 nmol of bilirubin h-1 nmol-1 HO-1 as compared to approximately 140-150 nmol of bilirubin h-1 nmol-1 for the WT form, which contains the 30 kDa contaminant. This is a 2-3-fold increase from the previously reported soluble 30 kDa HO-1, suggesting that the C-terminal 23 amino acids are essential for maximal catalytic activity. Because the membrane-spanning domain is present, the full-length hHO-1 has the potential to incorporate into phospholipid membranes, which can be reconstituted at known concentrations, in combination with other endoplasmic reticulum resident enzymes.

On the role of the termolecular reactions 2O2 + H2 → 2HO2 and 2O2 + H2 → H + HO2 + O2 in formation of the first radicals in hydrogen combustion: ab initio predictions of energy barriers.

PubMed

Monge-Palacios, M; Rafatijo, Homayoon

2017-01-18

We have investigated the role of termolecular reactions in the early chemistry of hydrogen combustion. We performed molecular chemical dynamics simulations using ReaxFF in LAMMPS to identify potential initial reactions for a 1 : 4 mixture of H 2  : O 2 in the NVT ensemble at density 276.3 kg m -3 and ∼3000 K (∼4000 atm) and ∼4000 K (∼5000 atm), and then characterized the saddle points for those reactions using ab initio methods: CCSD(T) = FC/cc-pVTZ//MP2/6-31G, CCSD(T) = FULL/aug-cc-pVTZ//CCSD = FC/cc-pVTZ and CASSCF MP2/6-31G//MP2/6-31G. The main initial reaction is H 2 + O 2 → H + HO 2 , frequently occurring in the presence of a second O 2 as a third body; that is, 2O 2 + H 2 → H + HO 2 + O 2 . The second most frequent reaction is 2O 2 + H 2 → 2HO 2 . We found three saddle points on the triplet PES of these termolecular reactions: one for 2O 2 + H 2 → H + HO 2 + O 2 and two for 2O 2 + H 2 → 2HO 2 . In the latter case, one has a symmetric structure consistent with simultaneous formation of two HO 2 and the other corresponds to a bimolecular reaction between O 2 and H 2 that is "interrupted" by a second O 2 before going to completion. The classical barrier height of the symmetric saddle point for 2O 2 + H 2 → 2HO 2 is 49.8 kcal mol -1 . The barrier to H 2 + O 2 → H + HO 2 is 58.9 kcal mol -1 . The termolecular reaction will be competitive with H 2 + O 2 → H + HO 2 only at sufficiently high pressures.

Beneficial use of serum ferritin and heme oxygenase-1 as biomarkers in adult-onset Still's disease: A multicenter retrospective study.

PubMed

Kirino, Yohei; Kawaguchi, Yasushi; Tada, Yoshifumi; Tsukamoto, Hiroshi; Ota, Toshiyuki; Iwamoto, Masahiro; Takahashi, Hiroki; Nagasawa, Kohei; Takei, Shuji; Horiuchi, Takahiko; Ichida, Hisae; Minota, Seiji; Ueda, Atsuhisa; Ohta, Akihide; Ishigatsubo, Yoshiaki

2018-01-11

Heme oxygenase (HO)-1 is a heme-degrading enzyme highly expressed in monocyte/macrophage, serum levels of which may be promising biomarker for adult-onset Still's disease (AOSD). We here report data on the use of serum ferritin and HO-1 levels in AOSD. Under the Hypercytokinemia Study Group collaboration, we collected sera from a total of 145 AOSD patients. Three independent experts judged whether the patients were definite AOSD depending on the clinical information. These 91 'definite AOSD' patients were further divided into active, remission, and relapse groups. Forty-six cases of systemic vasculitis, sepsis, etc. were included as disease controls. Serum ferritin and HO-1 levels were measured using ELISA. Associations between clinical symptoms, serum ferritin, and HO-1 were explored. Multivariate regression analysis was performed to identify independent variables associated with definite AOSD diagnosis. Serum ferritin and HO-1 levels were significantly higher in active and relapsed AOSD cases compared to disease controls, and were reduced by the treatment. Although a significant correlation was found between serum ferritin and HO-1 levels, a discrepancy was found in some cases such as iron-deficiency anemia. Receiver operating characteristic analysis identified optimal levels of serum ferritin (>819 ng/ml; sensitivity 76.1% and specificity 73.8%), and serum HO-1 (>30.2 ng/ml; sensitivity 84.8% and specificity 83.3%) that differentiated AOSD from controls. Interestingly, 88.9% of patients with AOSD who relapsed exceeded the cut-off value of serum HO-1 > 30.2 ng/ml, but only 50.0% exceeded serum ferritin >819 ng/ml (p = .013), suggesting that serum HO-1 levels may be a convenient indicator of AOSD disease status. Multivariate analysis identified neutrophilia, RF/ANA negativity, sore throat, and elevated serum HO-1 as independent variables associated with AOSD diagnosis. We confirmed that serum ferritin and HO-1 serve as highly specific and sensitive biomarkers for AOSD. A future prospective study with large sample size is necessary to determine whether these biomarkers could be included in Yamaguchi's Criteria.

Augmented-reality-based skills training for robot-assisted urethrovesical anastomosis: a multi-institutional randomised controlled trial.

PubMed

Chowriappa, Ashirwad; Raza, Syed Johar; Fazili, Anees; Field, Erinn; Malito, Chelsea; Samarasekera, Dinesh; Shi, Yi; Ahmed, Kamran; Wilding, Gregory; Kaouk, Jihad; Eun, Daniel D; Ghazi, Ahmed; Peabody, James O; Kesavadas, Thenkurussi; Mohler, James L; Guru, Khurshid A

2015-02-01

To validate robot-assisted surgery skills acquisition using an augmented reality (AR)-based module for urethrovesical anastomosis (UVA). Participants at three institutions were randomised to a Hands-on Surgical Training (HoST) technology group or a control group. The HoST group was given procedure-based training for UVA within the haptic-enabled AR-based HoST environment. The control group did not receive any training. After completing the task, the control group was offered to cross over to the HoST group (cross-over group). A questionnaire administered after HoST determined the feasibility and acceptability of the technology. Performance of UVA using an inanimate model on the daVinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) was assessed using a UVA evaluation score and a Global Evaluative Assessment of Robotic Skills (GEARS) score. Participants completed the National Aeronautics and Space Administration Task Load Index (NASA TLX) questionnaire for cognitive assessment, as outcome measures. A Wilcoxon rank-sum test was used to compare outcomes among the groups (HoST group vs control group and control group vs cross-over group). A total of 52 individuals participated in the study. UVA evaluation scores showed significant differences in needle driving (3.0 vs 2.3; P = 0.042), needle positioning (3.0 vs 2.4; P = 0.033) and suture placement (3.4 vs 2.6; P = 0.014) in the HoST vs the control group. The HoST group obtained significantly higher scores (14.4 vs 11.9; P 0.012) on the GEARS. The NASA TLX indicated lower temporal demand and effort in the HoST group (5.9 vs 9.3; P = 0.001 and 5.8 vs 11.9; P = 0.035, respectively). In all, 70% of participants found that HoST was similar to the real surgical procedure, and 75% believed that HoST could improve confidence for carrying out the real intervention. Training in UVA in an AR environment improves technical skill acquisition with minimal cognitive demand. © 2014 The Authors. BJU International © 2014 BJU International.

The Armed Force of the Philippines and Special Operations

DTIC Science & Technology

2004-12-01

Reader: Peter J . Gustaitis THIS PAGE INTENTIONALLY LEFT BLANK i REPORT DOCUMENTATION PAGE Form Approved...by: Kalev I. Sepp Thesis Advisor Peter J . Gustaitis Second Reader Gordon McCormick Chairman, Department of Defense Analysis iv...Father Blanco Rescue Operation: Basilan Province, May 7-15, 1993

76 FR 1165 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

..., individually and as co-trustee of The Charles R. Gesell Irrevocable Trust, and The Peter J. Gesell Irrevocable... Irrevocable Trust and The Peter J. Gesell Irrevocable Trust as part of The Gesell Family Group; to retain...

Optimizing the DoD Supply Chain for the Future Joint Force

DTIC Science & Technology

2013-05-01

4 Sunil Chopra and Peter Meindl, Supply Chain Management: Strategy, Planning, and Operation, 5th ed. (Boston: Pearson Education, Inc., 2013), 339...Arlington, VA: Lexington Institute, 2005. Chopra, Sunil and Peter Meindl. Supply Chain Management: Strategy, Planning, and Operation. 5th ed. Boston

Biomechanics of Distance Running.

ERIC Educational Resources Information Center

Cavanagh, Peter R., Ed.

Contributions from researchers in the field of running mechanics are included in the 13 chapters of this book. The following topics are covered: (1) "The Mechanics of Distance Running: A Historical Perspective" (Peter Cavanagh); (2) "Stride Length in Distance Running: Velocity, Body Dimensions, and Added Mass Effects" (Peter Cavanagh, Rodger…

ARC-2009-ACD09-0108-040

NASA Image and Video Library

2009-02-08

An SUV-sized Asteroid 2008TC# Impacts on October 7, 2008 in the Nubian Desert, Northern Sudan: Dr. Peter Jenniskens, NASA/SETI joined Muawia Shaddas of the University of Khartoum in leading an expedition on a search for samples. Peter Jenniskens meteorite. Photo Credit: NASA/SETI/P. Jenniskens

Editors on Unix

NASA Astrophysics Data System (ADS)

Clayton, C. A.

The purpose of this document is to give new users advice on how to choose which editor to use on Unix machines. Under Unix the default editors are considered to be unfriendly and many users prefer to use other more sophisticated alternatives. However, many such alternatives exist; there is not one single editor that everyone finds acceptable and hence each user must decide for himself or herself which to adopt.

The Lives and Hard Times of Magazine Editors in the Big Apple: A Report on the Society of Magazine Editors' Educators Seminar.

ERIC Educational Resources Information Center

English, John W.

This report chronicles the first Society of Magazine Editors' educators seminar, which was held in New York from May 13-17, 1974, and was attended by ten journalism faculty. The industry's concerns, as expressed through editors, are paper, printing, postage, people, and profit. The Magazine Publishers Association (MPA) seems mostly concerned with…

Views of Iranian medical journal editors on medical research publication.

PubMed

Etemadi, Arash; Raiszadeh, Farbod; Alaeddini, Farshid; Azizi, Fereidoun

2004-01-01

Medical journal editors play an important role in optimizing research publication. This study evaluates the views of Iranian medical journal editors, and their knowledge of medical publication standards. In May 2001, 51 editors from all journals approved by the Ministry of Health were invited to participate, 27 of whom completed the study. A self-administered questionnaire, based on the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URMS) was used which consisted of 28 questions in 9 subject fields. These fields included: peer review, conflicts of interest, authorship criteria, publication ethics, duplicate publication, mass media, advertising, competing manuscripts, and the Internet. The knowledge of the editors was assessed by a scoring system, with a range of -46 to +44 points. Twenty-three of the participants were editors-in-chief and 4 were managing editors. Their average age was 47.3 +/- 8.7 years and 25 were male. All journals were peer-reviewed, most having 2 or 3 reviewers for each manuscript. Of the journals, 92.6% accepted or rejected an article on the basis of the views of most reviewers and 52%, sometimes or always, used a statistician as a reviewer. Most of the editors believed that writing the first draft and designing the study are authorship criteria, and most of them believed that these 2 are stated in URMS. Seven journals (25.9%) never published advertisements. Among journals that sold advertisements, the most popular policy (85%) was the rejection of advertisements because they advertised harmful products. Out of 27 journals, 12 were accessible on the Internet, and 7 had independent websites. Of the editors, 81.5% thought that a website is useful for their journal. The average knowledge score of the editors was 6.5 +/- 7.5. None had a negative score, 33% scored zero, 45% obtained average scores and 22% obtained good scores. The results show that peer review is favored by all the editors studied, though it seems that journals do not follow clear-cut policies in this regard. Most of the editors, agreed with the statements of URMS to some extent and generally most have average to high knowledge of URMS.

A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mourad, Waleed F., E-mail: Waleed246@gmail.com; Department of Radiation Oncology, Beth Israel Medical Center, New York, NY; Packianathan, Satyaseelan

2012-03-01

Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patientsmore » were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.« less

Holmium laser enucleation of the prostate for treatment for large-sized benign prostate hyperplasia; is it a realistic endourologic alternative in developing country?

PubMed

Elshal, Ahmed M; Mekkawy, Ramy; Laymon, Mahmoud; Barakat, Tamer S; Elsaadany, Mohamed M; El-Assmy, Ahmed; El-Nahas, Ahmed R

2016-03-01

To assess the functional outcome and cumulative health-resource-related cost of holmium laser enucleation of the prostate (HoLEP) in comparison with transvesical open prostatectomy (TVOP) in a developing country. Matching of 92 HoLEP and 91 TVOP procedures was performed using resected prostate tissue weight as a sole matching criterion. Safety, efficacy, and accordingly health-related cost-efficiency of both procedures were statistically compared. Preoperative criteria and mean prostate size (166.7 ± 49.7, 161.4 ± 35.7 ml) were similar in HoLEP and TVOP, respectively; however, HoLEP treated more comorbid patients. Blood transfusion was 2.1 and 26.1 % after HoLEP and TVOP, respectively (P = 0.001). Median time to catheter removal and hospital stay was 2 days after HoLEP and 5 and 9 days, respectively, after TVOP (P < 0.001). On modified Clavien scale, grade per grade, there was no statistically significant difference between the two groups apart from local wound complications in TVOP group. High-grade complications (≥ grade 3) were reported in 3.2 and 6.5 % in HoLEP and TVOP, respectively (P = 0.49). Resected prostate tissue weight was independently associated with high-grade periprocedure complications (OR[95 %CI] 1.22[1.02:1.49], P = 0.03). Last follow-up symptom score, peak urine flow rate, residual urine, % PSA reduction, and need for reoperation were comparable between the two groups. HoLEP costs the hospital in the first 3 months 4111.8EP (575US$) versus 4305.4EP (602US$) for TVOP (P = 0.09). In high-volume hospital, HoLEP procedure seems to be equally safe and effective as TVOP with the advantages of minimally invasive procedures. Two years after adopting the technique, HoLEP equally costs the hospital as TVOP. Significant hospital cost savings are anticipated in subsequent cases.

Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

PubMed

Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

2015-09-01

The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of Nephrology.

Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pandey, Amit V., E-mail: amit@pandeylab.org; Flueck, Christa E.; Mullis, Primus E.

2010-09-24

Research highlights: {yields} Mutations in POR identified from patients lead to reduced HO-1 activities. {yields} POR mutation Y181D affecting FMN binding results in total loss of HO-1 activity. {yields} POR mutations A287P, C569Y and V608F, lost 50-70% activity. {yields} Mutations in FAD binding domain, R457H, Y459H and V492E lost all HO-1 activity. {yields} POR polymorphisms P228L, R316W, G413S, A503V and G504R have normal activity. -- Abstract: Human heme oxygenase-1 (HO-1) carries out heme catabolism supported by electrons supplied from the NADPH through NADPH P450 reductase (POR, CPR). Previously we have shown that mutations in human POR cause a rare formmore » of congenital adrenal hyperplasia. In this study, we have evaluated the effects of mutations in POR on HO-1 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified HO-1 to measure heme degradation in a coupled assay using biliverdin reductase. Here we show that mutations in POR found in patients may reduce HO-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had total loss of HO-1 activity, while POR mutations A287P, C569Y and V608F lost 50-70% activity. The POR variants P228L, R316W and G413S, A503V and G504R identified as polymorphs had close to WT activity. Loss of HO-1 activity may result in increased oxidative neurotoxicity, anemia, growth retardation and iron deposition. Further examination of patients affected with POR deficiency will be required to assess the metabolic effects of reduced HO-1 activity in affected individuals.« less

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction.

PubMed

Liu, Xiaoli; Simpson, Jeremy A; Brunt, Keith R; Ward, Christopher A; Hall, Sean R R; Kinobe, Robert T; Barrette, Valerie; Tse, M Yat; Pang, Stephen C; Pachori, Alok S; Dzau, Victor J; Ogunyankin, Kofo O; Melo, Luis G

2007-07-01

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

Abnormal neural activity of brain regions in treatment-resistant and treatment-sensitive major depressive disorder: a resting-state fMRI study.

PubMed

Guo, Wen-bin; Liu, Feng; Chen, Jin-dong; Gao, Keming; Xue, Zhi-min; Xu, Xi-jia; Wu, Ren-rong; Tan, Chang-lian; Sun, Xue-li; Liu, Zhe-ning; Chen, Hua-fu; Zhao, Jing-ping

2012-10-01

Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions. Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study. ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively. Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hot water, UV-C and superatmospheric oxygen packaging as hurdle techniques for maintaining overall quality of fresh-cut pomegranate arils.

PubMed

Maghoumi, Mahshad; Gómez, Perla A; Artés-Hernández, Francisco; Mostofi, Younes; Zamani, Zabihalah; Artés, Francisco

2013-03-30

In recent years there has been increasing consumer pressure to avoid the use of agrochemicals such as chlorine on fresh plant products for extending their shelf life. The combined use of eco-sustainable techniques may be an alternative. The effect of hot water (HW), ultraviolet-C (UV-C) light and high oxygen packaging (HO) on the overall quality of fresh-cut pomegranate arils stored under modified atmosphere packaging (MAP) for up to 14 days at 5 °C was studied. Arils extracted manually, washed with chlorine (100 µL L⁻¹ NaClO, pH 6.5, 5 °C water), rinsed and drained were exposed to single or combined (double and triple) hurdle techniques. The HW treatment consisted of a 30 s immersion in water at 55 °C followed by air surface drying. A 4.54 kJ m⁻² dose was used for the UV-C treatment before packaging. Active MAP with initial 90 kPa O₂ was used in the HO treatment. The respiration rate remained relatively constant throughout shelf life, with no differences among treatments. CO₂ accumulation was higher within HO packages. HW induced a slight reduction in total soluble solids, while no changes in titratable acidity were found. HO-treated arils had the highest phenolic content, while the lowest was found in HW-treated arils. The lowest antioxidant activity was found in HW + UV-C + HO and the highest in UV-C + HO and HO treatments. HW alone or in combination with UV-C and HO inhibited mesophile, mould and yeast growth, while UV-C + HO was most effective for controlling yeast and mould growth. UV-C and HO either alone or in combination are promising techniques to preserve the quality of pomegranate arils for up to 14 days at 5 °C. © 2012 Society of Chemical Industry.

Potential energy surface and quantum dynamics study of rovibrational states for HO(3) (X (2)A'').

PubMed

Braams, Bastiaan J; Yu, Hua-Gen

2008-06-07

An analytic potential energy surface has been constructed by fitting to about 28 thousand energy points for the electronic ground-state (X (2)A'') of HO(3). The energy points are calculated using a hybrid density functional HCTH and a large basis set aug-cc-pVTZ, i.e., a HCTH/aug-cc-pVTZ density functional theory (DFT) method. The DFT calculations show that the trans-HO(3) isomer is the global minimum with a potential well depth of 9.94 kcal mol(-1) with respect to the OH + O(2) asymptote. The equilibrium geometry of the cis-HO(3) conformer is located 1.08 kcal mol(-1) above that of the trans-HO(3) one with an isomerization barrier of 2.41 kcal mol(-1) from trans- to cis-HO(3). By using this surface, a rigorous quantum dynamics (QD) study has been carried out for computing the rovibrational energy levels of HO(3). The calculated results determine a dissociation energy of 6.15 kcal mol(-1), which is in excellent agreement with the experimental value of Lester et al. [J. Phys. Chem. A, 2007, 111, 4727.].

White up-conversion emission in Ho3+/Tm3+/Yb3+ tri-doped glass ceramics embedding BaF2 nanocrystals

NASA Astrophysics Data System (ADS)

Li, Chenxia; Xu, Shiqing; Ye, Rengguang; Deng, Degang; Hua, Youjie; Zhao, Shilong; Zhuang, Songlin

2011-04-01

Ho3+/Tm3+/Yb3+ tri-doped glass ceramics with white light emitting have been developed and demonstrated. Pumped by 980 nm laser diode (LD), intensive red, green and blue up-conversions (UC) were obtained. The green emission is assigned to Ho3+ ion and the blue emission is assigned to Tm3+ ion, whereas the red emission is the combination contribution of the Ho3+ and Tm3+ ions. The RGB intensities could be adjusted by tuning the rare-earth ion concentration and pump power intensity. Thus, multicolor of the luminescence, including perfect white light with CIE-X=0.329 and CIE-Y=0.342 in the 1931 CIE chromaticity diagram can be obtained in 0.15 Ho3+/0.2Tm3+/3Yb3+ tri-doped glass ceramics embedding BaF2 nanocrystals pumped by a single infrared laser diode source of 980 nm at 500 mW. The up-conversion luminescence mechanism of Yb3+ sensitize Ho3+ and Tm3+ ions and the energy transfer from Ho3+ to Tm3+ in oxy-fluoride silicate glass ceramics were analyzed.

Chemokine Signaling during Midline Epithelial Seam Disintegration Facilitates Palatal Fusion

PubMed Central

Suttorp, Christiaan M.; Cremers, Niels A.; van Rheden, René; Regan, Raymond F.; Helmich, Pia; van Kempen, Sven; Kuijpers-Jagtman, Anne M.; Wagener, Frank A.D.T.G.

2017-01-01

Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO), which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO) mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling. PMID:29164113

Molecular docking and molecular dynamics studies on the interactions of hydroxylated polybrominated diphenyl ethers to estrogen receptor alpha.

PubMed

Lu, Qun; Cai, Zhengqing; Fu, Jie; Luo, Siyi; Liu, Chunsheng; Li, Xiaolin; Zhao, Dongye

2014-03-01

Environmental estrogens have attracted great concerns. Recent studies have indicated that some hydroxylated polybrominated diphenyl ethers (HO-PBDEs) can interact with estrogen receptor (ER), and exhibit estrogenic activity. However, interactions between HO-PBDEs and ER are not well understood. In this work, molecular docking and molecular dynamics (MD) simulations were performed to characterize interactions of two HO-PBDEs (4'-HO-BDE30 and 4'-HO-BDE121) with ERα. Surflex-Dock was employed to reveal the probable binding conformations of the compounds at the active site of ERα; MD simulation was used to determine the detailed binding process. The driving forces of the binding between HO-PBDEs and ERα were van der Waals and electrostatic interactions. The decomposition of the binding free energy indicated that the hydrogen bonds between the residues Glu353, Gly521 and ligands were crucial for anchoring the ligands into the active site of ERα and stabilizing their conformations. The results showed that different interaction modes and different specific interactions with some residues were responsible for the different estrogenic activities of the two HO-PBDEs. Copyright © 2013 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinstein, J.; Bielski, H.J.

The rates of reaction of HO/sub 2/ and O/sub 2//sup -/ with hydrogen peroxide, known as the Haber--Weiss reactions, were studied by /sup 60/Co ..gamma.. radiolysis as a function of pH at 23.5/sup 0/C. The numerical values for the two rate constants, k/sub HO/sub 2/+H/sub 2/O/sub 2// = (0.50 +- 0.09) M/sup -1/ s/sup -1/ and k/sub O/sub 2/-+H/sub 2/O/sub 2// = (0.13 +- 0.07) M/sup -1/ s/sup -1/, were computed from molecular oxygen yields which result from the radiation-induced chain decomposition of aqueous hydrogen peroxide solutions. The experimental results are consistent with a chain mechanism which takes into accountmore » the dissociation of HO/sub 2/ in equilibrium O/sub 2//sup -/ + H/sup +/ (pK = 4.7) and the competition between the Haber--Weiss reactions (HO/sub 2/ + H/sub 2/O/sub 2/ and O/sub 2//sup -/ + H/sub 2/O/sub 2/) and the recombination reactions of the superoxide and perhydroxyl radicals (HO/sub 2/ + HO/sub 2/ and HO/sub 2/ + O/sub 2//sup -/).« less

How is research publishing going to progress in the next 20 years?: transcription of session for editors, associate editors, publishers and others with an interest in scientific publishing held at IADR meeting in Seattle on Wednesday, 20 March 2013.

PubMed

Eaton, Kenneth A; Rex Holland, G; Giannobile, William V; Hancocks, Stephen; Robinson, Peter G; Lynch, Christopher D

2014-03-01

On March 20th 2013, a one-hour session for Editors, Associate Editors, Publishers and others with an interest in scientific publishing was held at the IADR International Session in Seattle. Organised by Kenneth Eaton and Christopher Lynch (Chair and Secretary, respectively, of the British Dental Editors Forum), the meeting sought to bring together leading international experts in dental publishing, as well as authors, reviewers and students engaged in research. The meeting was an overwhelming success, with more than 100 attendees. A panel involving four leading dental editors led a discussion on anticipated developments in publishing dental research with much involvement and contribution from audience members. This was the third such meeting held at the IADR for Editors, Associate Editors, Publishers and others with an interest in scientific publishing. A follow-up session will take place in Cape Town on 25 June 2014 as part of the annual IADR meeting. The transcript of the Seattle meeting is reproduced in this article. Where possible speakers are identified by name. At the first time of mention their role/position is also stated, thereafter only their name appears. We are grateful to Stephen Hancocks Ltd. for their generous sponsorship of this event. For those who were not able to attend the authors hope this article gives a flavour of the discussions and will encourage colleagues to attend future events. Involvement is open to Editors, Associate Editors, Publishers and others with an interest in scientific publishing. It is a very open group and all those with an interest will be welcome to join in. Copyright © 2014 Elsevier Ltd. All rights reserved.

Heterogeneous Uptake of HO2 Radicals onto Submicron Atmospheric Aerosols

NASA Astrophysics Data System (ADS)

Matthews, P. S.; George, I. J.; Brooks, B.; Whalley, L. K.; Baeza-Romero, M. T.; Heard, D. E.

2012-12-01

OH and HO2 (HOx) radicals are closely coupled and OH is responsible for the majority of the oxidation in the troposphere and controls the concentrations of many trace species. Therefore, it is important to be able to accurately predict HOx concentrations. However, some field measurement studies have reported significantly lower HO2 radical concentrations than calculated by constrained box models using detailed chemical mechanisms. Although the inclusion of halogen chemistry into the mechanisms can explain much of the differences in the marine boundary layer (MBL) (1,2), HO2 uptake by aerosols has been suggested as a possible sink in the MBL (2), the Arctic troposphere (3) and the upper troposphere (4). There have been very few laboratory studies (5,6) on HO2 uptake by aerosols and the rates and mechanism is still uncertain. The HO2 uptake coefficients were measured for a variety of atmospherically relevant inorganic and organic aerosols. The measurements were performed using an aerosol flow tube combined with a Fluorescence Assay by Gas Expansion (FAGE) detector. The sensitive FAGE cell allowed low HO2 concentrations (108-109 molecule cm-3) to be injected into the flow tube using a moveable injector. By moving the injector along the flow tube, position dependent HO2 decays were able to be recorded which when plotted against the total aerosol surface area allowed an uptake coefficient to be obtained. The aerosols were generated using an atomiser or by homogeneous nucleation and the total aerosol surface area was measured using a Scanning Mobility Particle Sizer. The HO2 uptake coefficient (γ) was measured at room temperature for dry inorganic salts and dry organics (γ< 0.004), wet inorganic salts and wet organics (γ= 0.002-0.005), wet copper doped ammonium sulfate aerosols (γ= 0.28± 0.05) and ammonium sulfate aerosols doped with different molar amounts of iron (γ= 0.003-0.06). The pH dependence of the HO2 uptake coefficient was investigated, however no dependence was observed. A time dependence has been observed, with higher HO2 uptake coefficients measured at short reaction times with the uptake coefficient decreasing at longer times. A HO2 concentration dependence has also been observed whereby a higher uptake coefficient is measured at lower HO2 concentrations. The time dependence and HO2 concentration dependence may suggest an aerosol saturation mechanism. The HO2 uptake temperature dependence is currently being investigated, as well as uptake on to a wider range of inorganic and organic aerosols. This work was supported by the National Environment Research Council under grant number NE/F020651/1. PSJM is grateful to NERC for a research studentship. References (1) Sommariva, R. et al. Atmos. Chem. Phys.2006, 6, 1135-1153. (2) Whalley, L.K. et al. Atmos. Chem. Phys. 2010, 10, 1555-1576. (3) Mao, J. et al. Atmos. Chem. Phys. 2010, 10, 5823-5838. (4) Jaegle, L. et al. J. Geophys. Atm. 2000, 105, 3877-3892. (5) Taketani, F. et al. J. Phys. Chem. 2008, 112, 2370-2377. (6) Thornton, J. et al. J. Geophys. Atm. 2005, 110, D08309.

Telling the Public--It's Science Week

ERIC Educational Resources Information Center

Auty, Geoff

2011-01-01

This article describes an opportunity to engage the public in demonstrating and explaining some aspects of science. About 10 years ago, the author met Peter Evennett in the ASE Conference exhibition. Peter was a member of the Leeds Philosophical and Literary Society and currently its president. As a contribution to "Science Week" (which…

Team Leader: Tom Peters--TAP Information Services

ERIC Educational Resources Information Center

Library Journal, 2005

2005-01-01

Tom Peters packs 36 hours of work into the confines of a 24-hour day. Without breaking a sweat, he juggles multiple collaborative projects, which currently include an Illinois academic library shared storage facility; a multistate virtual reference and instruction service for blind and visually impaired individuals (InfoEyes); a virtual meeting…

Peter Drucker, Knowledge Work, and the Structure of Schools.

ERIC Educational Resources Information Center

Tucker, Marc S.

1988-01-01

Discusses Peter Drucker's recommendations in "The Age of Discontinuity" (1969) concerning the decline of manual work, the ascendancy of knowledge work, and the relationship between economic stability and an educated, productive work force. Applies Drucker's principles to the movement to restructure schools, which aims to make line…

Instruction in the Making: Peter Ramus and the Beginnings of Modern Schooling.

ERIC Educational Resources Information Center

Hamilton, David

This paper examines educational practice between 1450-1650, highlighting 16th century educationist, Peter Ramus, whose work is remembered in the "History of Western Philosophy" as fostering a "pedagogic marvel." Ramus' work has received scant attention from English-speaking educationists, and his niche within the educational…

R. S. Peters: The Reasonableness of Ethics

ERIC Educational Resources Information Center

Haynes, Felicity

2013-01-01

This article will begin by examining the extent to which R. S. Peters merited the charge of analytic philosopher. His background in social psychology allowed him to become more pragmatic and grounded in social conventions and ordinary language than the analytic philosophers associated with empiricism, and his gradual shift from requiring internal…

ARC-2009-ACD09-0108-039

NASA Image and Video Library

2009-02-08

An SUV-sized Asteroid 2008TC# Impacts on October 7, 2008 in the Nubian Desert, Northern Sudan: Dr. Peter Jenniskens, NASA/SETI joined Muawia Shaddas of the University of Khartoum in leading an expedition on a search for samples. (Peter Jenniskens pointing - finds the brick) Photo Credit: NASA/SETI/P. Jenniskens

ARC-2009-ACD09-0108-038

NASA Image and Video Library

2009-02-08

An SUV-sized Asteroid 2008TC# Impacts on October 7, 2008 in the Nubian Desert, Northern Sudan: Dr. Peter Jenniskens, NASA/SETI joined Muawia Shaddas of the University of Khartoum in leading an expedition on a search for samples. Peter Jenniskens finds the brick. Photo Credit: NASA/SETI/P. Jenniskens

Workplace Evolution without Practitioners

ERIC Educational Resources Information Center

Walker, Barrington D.

2014-01-01

In general management theory, the choosing of a nominee for a job based on their current and typically exceptional performance within a given occupation rather than on qualifications for an intended position is referred to as "The Peter Principle" (Peter and Hull, 1969). If an incumbent is incapable of performing at the anticipated level…

Globalisation in Africa: Reflecting on Peter Jarvis's Superstructure and Substructure Model

ERIC Educational Resources Information Center

Preece, Julia

2017-01-01

This paper reflects on Peter Jarvis' book "Globalisation, lifelong learning and the learning society," volume 2--in which he describes human learning within a global context and factors contributing to globalisation. He describes the relationship of power between countries manifested as the superstructure and sub structure. The paper…

Marginal Experiments: Peter Brook and Stepping out Theatre Company

ERIC Educational Resources Information Center

Harpin, Anna

2010-01-01

This article juxtaposes the recent work of Peter Brook with a Bristol-based mental health service-user collective--Stepping Out Theatre Company. Informed by field-work with the company, this chapter explores the aesthetic and political relationship between professional, experimental theatre work and community-based performance practice. Drawing…

The Brigade Combat Team - Stability and Security Force Assistance Operations

DTIC Science & Technology

2010-02-22

it makes absolute sense to embed these transition teams within the brigade, assigned within the brigade. The beauty of this is that it allows the...accessed October 19, 2009). 22 COL Peter Newell, “Department of Defense Bloggers Roundtable with COL Peter Newell, Subject: Completion of Advise and

Teaching Behavior Analysis and Psychology in Social Context: An Interview with Peter Harzem.

ERIC Educational Resources Information Center

Buskist, William

2000-01-01

Presents an interview with Peter Harzem, the Hudson Professor of Psychology at Auburn University (Alabama). Addresses such issues as teaching students about behavior analysis, the differences between classical and operant conditioning, reinforcement and behaviorism, and how one can become a better teacher. (CMK)

The Possibilities of Transformation: Critical Research and Peter McLaren

ERIC Educational Resources Information Center

Porfilio, Brad J.

2006-01-01

The purpose of this paper is to unveil how Peter McLaren's revolutionary brand of pedagogy, multiculturalism, and research colored my two-year qualitative research study, which unearthed twenty White female future teachers' experiences and perceptions in relationship to computing technology and male-centered computing culture. His ideas positioned…

Richard Peters and Valuing Authenticity

ERIC Educational Resources Information Center

Degenhardt, M. A. B.

2009-01-01

Richard Peters has been praised for the authenticity of his philosophy, and inquiry into aspects of the development of his philosophy reveals a profound authenticity. Yet authenticity is something he seems not to favour. The apparent paradox is resolved by observing historical changes in the understanding of authenticity as an important value.…

A Critique of Peter Jarvis's Conceptualisation of the Lifelong Learner in the Contemporary Cultural Context

ERIC Educational Resources Information Center

Bagnall, Richard G.

2017-01-01

This paper examines Peter Jarvis's conceptualisation of lifelong learners, who are seen as being the individual products of their learning engagements, constrained by their individual biological potentials. They are presented as seeking existentially authentic resolution to dialectically oppositional disjunctures between their individual…

76 FR 13271 - Gulf & Ohio Railways, Inc., H. Peter Claussen and Linda C. Claussen-Continuance in Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. FD 35414] Gulf & Ohio Railways, Inc., H. Peter Claussen and Linda C. Claussen--Continuance in Control Exemption--Lancaster & Chester Railroad, LLC AGENCY: Surface Transportation Board, DOT. ACTION: Correction to notice of exemption...

On the Worthwhileness of Theoretical Activities

ERIC Educational Resources Information Center

Hand, Michael

2009-01-01

R.S. Peters' arguments for the worthwhileness of theoretical activities are intended to justify education per se, on the assumption that education is necessarily a matter of initiating people into theoretical activities. If we give up this assumption, we can ask whether Peters' arguments might serve instead to justify the academic curriculum over…

ARC-2009-ACD09-0108-036

NASA Image and Video Library

2009-02-08

An SUV-sized Asteroid 2008TC# Impacts on October 7, 2008 in the Nubian Desert, Northern Sudan: Dr. Peter Jenniskens, NASA/SETI joined Muawia Shaddas of the University of Khartoum in leading an expedition on a search for samples. Peter Jenniskens finds meteorites 1) Photo Credit: NASA/SETI/P. Jenniskens

ARC-2009-ACD09-0108-035

NASA Image and Video Library

2009-02-08

An SUV-sized Asteroid 2008TC# Impacts on October 7, 2008 in the Nubian Desert, Northern Sudan: Dr. Peter Jenniskens, NASA/SETI joined Muawia Shaddas of the University of Khartoum in leading an expedition on a search for samples. Peter Jenniskens examines 2nd trip finds) Photo Credit: NASA/SETI/P. Jenniskens

Heme oxygenase attenuates angiotensin II-mediated superoxide production in cultured mouse thick ascending loop of Henle cells.

PubMed

Kelsen, Silvia; Patel, Bijal J; Parker, Lawson B; Vera, Trinity; Rimoldi, John M; Gadepalli, Rama S V; Drummond, Heather A; Stec, David E

2008-10-01

Heme oxygenase (HO)-1 induction can attenuate the development of angiotensin II (ANG II)-dependent hypertension. However, the mechanism by which HO-1 lowers blood pressure is not clear. The goal of this study was to test the hypothesis that induction of HO-1 can reduce the ANG II-mediated increase in superoxide production in cultured thick ascending loop of Henle (TALH) cells. Studies were performed on an immortalized cell line of mouse TALH (mTALH) cells. HO-1 was induced in cultured mTALH cells by treatment with cobalt protoporphyrin (CoPP, 10 microM) or hemin (50 microM) or by transfection with a plasmid containing the human HO-1 isoform. Treatment of mTALH cells with 10(-9) M ANG II increased dihydroethidium (DHE) fluorescence (an index of superoxide levels) from 35.5+/-5 to 136+/-18 relative fluorescence units (RFU)/microm2. Induction of HO-1 via CoPP, hemin, or overexpression of the human HO-1 isoform significantly reduced ANG II-induced DHE fluorescence to 64+/-5, 64+/-8, and 41+/-4 RFU/microm2, respectively. To determine which metabolite of HO-1 is responsible for reducing ANG II-mediated increases in superoxide production in mTALH cells, cells were preincubated with bilirubin or carbon monoxide (CO)-releasing molecule (CORM)-A1 (each at 100 microM) before exposure to ANG II. DHE fluorescence averaged 80+/-7 RFU/microm2 after incubation with ANG II and was significantly decreased to 55+/-7 and 53+/-4 RFU/microm2 after pretreatment with bilirubin and CORM-A1. These results demonstrate that induction of HO-1 in mTALH cells reduces the levels of ANG II-mediated superoxide production through the production of both bilirubin and CO.

Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

PubMed

Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

2015-08-01

To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

Relationship between boundary layer heights and growth rates with ground-level ozone in Houston, Texas

NASA Astrophysics Data System (ADS)

Haman, C. L.; Couzo, E.; Flynn, J. H.; Vizuete, W.; Heffron, B.; Lefer, B. L.

2014-05-01

Measurements and predictions of ambient ozone (O3), planetary boundary layer (PBL) height, the surface energy budget, wind speed, and other meteorological parameters were made near downtown Houston, Texas, and were used to investigate meteorological controls on elevated levels of ground-level O3. Days during the study period (1 April 2009 to 31 December 2010 for measurements and 15 April 2009 to 17 October 2009 for modeled) were classified into low (LO3) and high ozone (HO3) days. The majority of observed high HO3 days occurred in a postfrontal environment. Observations showed there is not a significant difference in daily maximum PBL heights on HO3 and LO3 days. Modeling results showed large differences between maximum PBL heights on HO3 and LO3 days. Nighttime and early morning observed and modeled PBL heights are consistently lower on HO3 days than on LO3 days. The observed spring LO3 days had the most rapid early morning PBL growth (~350 m h-1) while the fall HO3 group had the slowest (~200 m h-1). The predicted maximum average hourly morning PBL growth rates were greater on HO3 (624 m h-1) days than LO3 days (361 m h-1). Observed turbulent mixing parameters were up to 2-3 times weaker on HO3 days, which indicate large-scale subsidence associated with high-pressure systems (leading to clear skies and weak winds) substantially suppresses mixing. Lower surface layer ventilation coefficients were present in the morning on HO3 days in the spring and fall, which promotes the accumulation of O3 precursors near the surface.

Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector.

PubMed

Tang, Yao Liang; Tang, Yi; Zhang, Y Clare; Qian, Keping; Shen, Leping; Phillips, M Ian

2005-10-04

The goal of this study was to modify mesenchymal stem cells (MSCs) cells with a hypoxia-regulated heme oxygenase-1 (HO-1) plasmid to enhance the survival of MSCs in acute myocardial infarction (MI) heart. Although stem cells are being tested clinically for cardiac repair, graft cells die in the ischemic heart because of the effects of hypoxia/reoxygenation, inflammatory cytokines, and proapoptotic factors. Heme oxygenase-1 is a key component in inhibiting most of these factors. Mesenchymal stem cells from bone marrow were transfected with either HO-1 or LacZ plasmids. Cell apoptosis was assayed in vitro after hypoxia-reoxygen treatment. In vivo, 1 x 10(6) of male MSC(HO-1), MSC(LacZ), MSCs, or medium was injected into mouse hearts 1 h after MI (n = 16/group). Cell survival was assessed in a gender-mismatched transplantation model. Apoptosis, left ventricular remodeling, and cardiac function were tested in a gender-matched model. In the ischemic myocardium, the MSC(HO-1) group had greater expression of HO-1 and a 2-fold reduction in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling-positive cells compared with the MSC(LacZ) group. At seven days after implantation, the survival MSC(HO-1) was five-fold greater than the MSC(LacZ) group; MSC(HO-1) also attenuated left ventricular remodeling and enhanced the functional recovery of infarcted hearts two weeks after MI. A hypoxia-regulated HO-1 vector modification of MSCs enhances the tolerance of engrafted MSCs to hypoxia-reoxygen injury in vitro and improves their viability in ischemic hearts. This demonstration is the first showing that a physiologically inducible vector expressing of HO-1 genes improves the survival of stem cells in myocardial ischemia.

Lack of evidence for the presence of emerging HoBi-like viruses in North American fetal bovine serum lots.

PubMed

Bauermann, Fernando V; Flores, Eduardo F; Falkenberg, Shollie M; Weiblen, Rudi; Ridpath, Julia F

2014-01-01

The detection of an emerging pestivirus species, "HoBi-like virus," in fetal bovine serum (FBS) labeled as U.S. origin, but packaged in Europe, raised concerns that HoBi-like virus may have entered the United States. In the current study, 90 lots of FBS originating in North America (NA) were screened for pestivirus antigen and antibodies. Lots in group 1 (G1, 72 samples) and group 2 (G2, 9 samples) originated in NA and were packaged in the United States. Group 3 (G3) was composed of 9 lots collected in NA and processed in Europe. Lots in G1 were claimed negative for Bovine viral diarrhea virus (BVDV), while lots in G2 and G3 were claimed positive by the commercial processor. All lots in G1 and G2 tested negative by reverse transcription polymerase chain reaction (RT-PCR) using HoBi-like-specific primers. Two G1 lots tested positive by BVDV RT-PCR. One of these was also positive by virus isolation. All G2 lots were positive by BVDV RT-PCR. In addition, four G2 lots were VI positive while 1 lot was antigen-capture enzyme-linked immunosorbent assay (ELISA) positive. Two G3 lots were positive by HoBi-like-specific RT-PCR tests. All lots were negative for HoBi_D32/00 neutralizing antibodies. Seven lots (4 G1; 1 G2; 2 G3) had antibodies against BVDV by virus neutralization and/or antigen-capture ELISA. While there is no evidence of HoBi-like viruses in NA based on tested samples, further studies are required to validate HoBi-like virus-free status and develop means to prevent the spread of HoBi-like virus into NA.

Heme oxygenase-1 protects INF-gamma primed endothelial cells from Jurkat T-cell adhesion.

PubMed

Du, D; Chang, S; Chen, B; Zhou, H; Chen, Z K

2007-12-01

The heme oxygenase-1 (HO-1) system is associated with the rate-limiting step of conversion of heme, one of the most critical roles in cytoprotective mechanisms. Our study investigated its potential role in protection of endothelial cells from T cells. The recombinant plasmid pcDNA3-HO-1 was transfected into endothelial cells. Indirect fluorescent staining was used to examine the expression of HO-1 protein. Then endothelial cells primed by INF-gamma were mixed in culture with Jurkat T cells labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE). The number of adhesive Jurkat T cells was determined using FACS to evaluate the adhesion effect. After being cultured with endothelial cells, the cell cycle of Jurkat T cells was detected using FACS. Expression of HO-1 on endothelial cells conferred significant protection against Jurkat T-cell-mediated adhesion. The rate of Jurkat T-cell adhesions was reduced to 19.06%, in contrast with 31.42% in the control group (P<.05). After using ZnPP, an inhibitor of HO-1, the rate of Jurkat T-cell adhesion recovered to 29.08%. The binding activities between endothelial cells and Jurkat T cells was blocked by HO-1 expression. The proliferation of Jurkat T cells was inhibited after culture with endothelial cells, which had been transfected with HO-1, which blocked cell cycle entry of T cells. More than 60% of Jurkat T cells remained in G0/G1 compared with 40% among the control group. HO-1 directly protected endothelial cells primed by INF-gamma from Jurkat T cells and down-regulated the expression of HLA-DR on the surface of endothelial cells. These results indicated that transgenic expression of HO-1 may be useful to prevent lymphocytes from responding to endothelial cells.

Butein induction of HO-1 by p38 MAPK/Nrf2 pathway in adipocytes attenuates high-fat diet induced adipose hypertrophy in mice.

PubMed

Wang, Zheng; Ka, Sun-O; Lee, Youngyi; Park, Byung-Hyun; Bae, Eun Ju

2017-03-15

Adipose tissue inflammation and oxidative stress are key components in the development of obesity and insulin resistance. Heme oxygenase (HO)-1 in adipocytes protects against obesity and adipose dysfunction. In this study, we report the identification of butein, a flavonoid chalcone, as a novel inducer of HO-1 expression in adipocytes in vitro and in vivo. Butein upregulated HO-1 mRNA and protein expression in 3T3-L1 adipocytes, accompanied by Kelch-Like ECH-Associated Protein (Keap) 1 degradation and increase in the nuclear level of nuclear factor erythroid 2-related factor 2 (Nrf2). Butein modulation of Keap1 and Nrf2 as well as HO-1 upregulation was reversed by pretreatment with p38 MAPK inhibitor SB203580, indicating the involvement of p38 MAPK in butein activation of Nrf2 in adipocytes. In addition, HO-1 activation by butein led to the inhibitions of reactive oxygen species and adipocyte differentiation, as evidenced by the fact that butein repression of reactive oxygen species and adipogenesis was reversed by pretreatment with HO-1 inhibitor SnPP. Induction of HO-1 expression by butein was also demonstrated in the adipose tissue of C57BL/6 mice fed a high-fat diet administered along with butein for three weeks, and correlated with the inhibitions of adiposity and adipose tissue inflammation, which were reversed by co-administration of SnPP. Altogether, our results demonstrate that butein activates the p38 MAPK/Nrf2/HO-1 pathway to act as a potent inhibitor of adipose hypertrophy and inflammation in a diet-induced obesity model and thus has potential for suppressing obesity-linked metabolic syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of chemical fingerprints in long-range transport of burning induced upper tropospheric ozone from Colorado to the North Atlantic Ocean.

PubMed

Jeon, Wonbae; Choi, Yunsoo; Souri, Amir Hossein; Roy, Anirban; Diao, Lijun; Pan, Shuai; Lee, Hwa Woon; Lee, Soon-Hwan

2018-02-01

This study investigates a significant biomass burning (BB) event occurred in Colorado of the United States in 2012 using the Community Multi-scale Air Quality (CMAQ) model. The simulation reasonably reproduced the significantly high upper tropospheric O 3 concentrations (up to 145ppb) caused by BB emissions. We find the BB-induced O 3 was primarily affected by chemical reactions and dispersion during its transport. In the early period of transport, high NO x and VOCs emissions caused O 3 production due to reactions with the peroxide and hydroxyl radicals, HO 2 and OH. Here, NO x played a key role in O 3 formation in the BB plume. The results indicated that HO 2 in the BB plume primarily came from formaldehyde (HCHO+hv=2HO 2 +CO), a secondary alkoxy radical (ROR=HO 2 ). CO played an important role in the production of recycled HO 2 (OH+CO=HO 2 ) because of its abundance in the BB plume. The chemically produced HO 2 was largely converted to OH by the reactions with NO (HO 2 +NO=OH+NO 2 ) from BB emissions. This is in contrast to the surface, where HO 2 and OH are strongly affected by VOC and HONO, respectively. In the late stages of transport, the O 3 concentration was primarily controlled by dispersion. It stayed longer in the upper troposphere compared to the surface due to sustained depletion of NO x . Sensitivity analysis results support that O 3 in the BB plume is significantly more sensitive to NO x than VOCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Calculation of the rate constant for state-selected recombination of H+O2(v) as a function of temperature and pressure

NASA Astrophysics Data System (ADS)

Teitelbaum, Heshel; Caridade, Pedro J. S. B.; Varandas, António J. C.

2004-06-01

Classical trajectory calculations using the MERCURY/VENUS code have been carried out on the H+O2 reactive system using the DMBE-IV potential energy surface. The vibrational quantum number and the temperature were selected over the ranges v=0 to 15, and T=300 to 10 000 K, respectively. All other variables were averaged. Rate constants were determined for the energy transfer process, H+O2(v)-->H+O2(v''), for the bimolecular exchange process, H+O2(v)-->OH(v')+O, and for the dissociative process, H+O2(v)-->H+O+O. The dissociative process appears to be a mere extension of the process of transferring large amounts of energy. State-to-state rate constants are given for the exchange reaction, and they are in reasonable agreement with previous results, while the energy transfer and dissociative rate constants have never been reported previously. The lifetime distributions of the HO2 complex, calculated as a function of v and temperature, were used as a basis for determining the relative contributions of various vibrational states of O2 to the thermal rate coefficients for recombination at various pressures. This novel approach, based on the complex's ability to survive until it collides in a secondary process with an inert gas, is used here for the first time. Complete falloff curves for the recombination of H+O2 are also calculated over a wide range of temperatures and pressures. The combination of the two separate studies results in pressure- and temperature-dependent rate constants for H+O2(v)(+Ar)⇄HO2(+Ar). It is found that, unlike the exchange reaction, vibrational and rotational-translational energy are liabilities in promoting recombination.