WorldWideScience

Sample records for research foundation nrf

  1. Mesothelioma Applied Research Foundation

    Science.gov (United States)

    ... Foundation Experts Can Answer Your Questions! The Mesothelioma Applied Research Foundation's team of experts is available to answer ... a law firm. Read more about the Mesothelioma Applied Research Foundation . TO GET HELP CALL: (877) End-Meso ...

  2. Intracranial Hypertension Research Foundation

    Science.gov (United States)

    ... PARTNERSHIPS Meet our Fundraising Partners Tweet Welcome Intracranial hypertension (IH) is the general term for the neurological ... high. (Old names for IH include Benign Intracranial Hypertension and Pseudotumor Cerebri). The Intracranial Hypertension Research Foundation ...

  3. Lymphoma Research Foundation

    Science.gov (United States)

    ... Follow LRF Watch LRF Contact Us National Headquarters Wall Street Plaza 88 Pine Street, Suite 2400 | New York, NY 10005 212-349-2910 | 212-349-2886 Fax LRF@lymphoma.org LRF Helpline 800-500-9976 Helpline@lymphoma.org © 2012 Lymphoma Research Foundation | Privacy Policy

  4. Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    1979-01-01

    The last day of March 1978 marked the completion of the first 3 years of operation of the Radiation Effects Research Foundation in Hiroshima and Nagasaki. RERF was established on 1 April 1975 as successor to the Atomic Bomb Casualty Commission which had been in continuous operation since 1947. This record of the first 3 years of operation consists of selected reports and other documents prepared in the course of conducting the business of RERF and includes a brief history, a late radiation effects that might be conducted at RERF. The wisdom and thought given to the research program and its operation by the Scientific Council and the Board of Directors is reflected in the minutes of their meetings which are included in the Appendix. (Mori, K.)

  5. Multiple Myeloma Research Foundation

    Science.gov (United States)

    ... MMRF Founder Kathy Giusti named 1 of 100 Visionaries of our time by the Einstein Foundation Learn More September 8, 2017 Tom Brokaw gives inspiring speech at MMRF Leadership Circle Summit on how his life was changed, ...

  6. American Vitiligo Research Foundation

    Science.gov (United States)

    ... Place Vitiligo Voices Contact Welcome to The American Vitiligo Foundation Home Page Top Isabella T., California An ... 20.00 USD 20 for - 35.00 USD Vitiligo Doesn't Scare Me by Kim Kirkland Kim ...

  7. Diabetes Research Institute Foundation

    Science.gov (United States)

    ... Video Be Part of the Cure Commitment to Stem Cell Research Exercise + Drug Therapy Tibi Creates Garment to Benefit ... Million Brenda Novak's Online Auction Cord Blood-Derived Stem ... Highlights DRI Research Diamond Ball 2009 DRI/DRIF Press Releases Historic ...

  8. Progeria Research Foundation, Inc.

    Science.gov (United States)

    ... Million Views – Celebrate with Us! Sam’s talk, "My Philosophy for a Happy Life", has inspired over 25 ... July 11th, 2016 | 0 Comments PRF Continues Aggressive Research Agenda Events November 25, 2017 in Verona, NJ: ...

  9. FRAXA Research Foundation

    Science.gov (United States)

    ... on YouTube What is Fragile X? Symptoms Cause Diagnosis Treatment Meet our Kids Newsroom Our Research How Close ... Subscribe to e-News Shop Donate ... the most common inherited cause of autism. In Their Own Words: Reports from the International ...

  10. Experimental Research of Engine Foundations

    Directory of Open Access Journals (Sweden)

    Violeta-Elena Chiţan

    2004-01-01

    Full Text Available This paper tries a compact presentation of experimental research of engine-foundations. The dynamic phenomena are so complex, that the vibrations cannot be estimated in the design stage. The design engineer of an engine foundation must foresee through a dynamic analysis of the vibrations, those measures that lead to the avoidance or limiting of the bad effects caused by the vibrations.

  11. Sandia National Laboratories: Research: Research Foundations: Engineering

    Science.gov (United States)

    Foundations Bioscience Computing & Information Science Electromagnetics Engineering Science Geoscience Mexico Small Business Assistance Program Sandia Science & Technology Park Careers Community Library Events Careers View All Jobs Students & Postdocs Internships & Co-ops Fellowships

  12. NCI collaborates with Multiple Myeloma Research Foundation

    Science.gov (United States)

    The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

  13. Research Award: Foundations for Innovation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-09-07

    Sep 7, 2016 ... The Foundations for Innovation program wishes to better ... disciplines: science, technology and innovation policy; development studies; or economics. ... research to local, national, and/or regional policy debates in Africa.

  14. Orthopaedic research and education foundation and industry.

    Science.gov (United States)

    Wurth, Gene R; Sherr, Judy H; Coffman, Thomas M

    2003-07-01

    Members of orthopaedic industry commit a significant amount of funds each year to support research and education programs that are directly related to their product(s). In addition, industry supports organizations such as the Orthopaedic Research and Education Foundation. The relationship between the Orthopaedic Research and Education Foundation and industry began in the early 1980s. The support to the Orthopaedic Research and Education Foundation from industry primarily has come in the form of unrestricted grants. These grants best can be looked at as an investment rather than a contribution. This form of giving, once called corporate philanthropy is more accurately referred to as strategic philanthropy. Members of industry make these investments to enhance their reputations, build brand awareness, market their products and services, improve employee morale, increase customer loyalty, and establish strategic alliances. The specialty of orthopaedics is among the leaders in medicine in the amount of funding raised within the specialty for research and education programs. This is because of the amount of support from members of industry and the surgeons. During the past 15 years, 40% of the annual support to the Orthopaedic Research and Education Foundation has come from industry and the balance has come from surgeons and members of lay public. Future industry support of the Orthopaedic Research and Education Foundation and other organizations within the specialty of orthopaedics will be dependent on the continued demonstration of tangible returns in areas described.

  15. Sandia National Laboratories: Research: Research Foundations: Nanodevices

    Science.gov (United States)

    Technology Partnerships Business, Industry, & Non-Profits Government Universities Center for Mexico Small Business Assistance Program Sandia Science & Technology Park Careers Community support for research; technology advancement and maturation; and small-lot, fast-turn prototyping Our

  16. Annual report of Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    1980-01-01

    The Radiation Effects Research Foundation was established in April, 1975, as a private nonprofit Japanese Foundation supported equally by the Government of Japan through the Ministry of Health and Welfare, and the Government of the United States through the National Academy of Sciences under contract with the Energy Research and Development Administration. First, the messages from the chairman and the vice-chairman are described. In the annual report, the review of ABCC-RERF studies of atomic bomb survivors, the summary of research activities, the research projects, the technical report abstracts, the research papers published in Japanese and foreign journals, and the oral presentation and lectures, all from April 1, 1978, to March 31, 1979, are reported. Also the report from the Secretariat and the appendixes are given. The surveys and researches carried out in Hiroshima and Nagasaki have offered very valuable informations to the atomic bomb survivors. Many fears were eliminated, medical interests were given to the serious effects of the exposure to atomic bombs, and many things concerning the cancer induced by radiation were elucidated. The knowledges obtained will save many human lives in future by utilizing them for setting up the health and safety standard in the case of handling ionizing radiation. The progress in researches such as life span study, adult health study, pathology study, genetics program, special cancer program and so on is reported. (Kako, I.)

  17. Cultural humility: essential foundation for clinical researchers.

    Science.gov (United States)

    Yeager, Katherine A; Bauer-Wu, Susan

    2013-11-01

    Cultural humility is a process of self-reflection and discovery in order to build honest and trustworthy relationships. It offers promise for researchers to understand and eliminate health disparities, a continual and disturbing problem necessitating attention and action on many levels. This paper presents a discussion of the process of cultural humility and its important role in research to better understand the perspectives and context of the researcher and the research participant. We discern cultural humility from similar concepts, specifically cultural competence and reflexivity. We will also explore ways to cultivate cultural humility in the context of human subjects research. Mindfulness is one approach that can be helpful in enhancing awareness of self and others in this process. With a foundation in cultural humility, nurse researchers and other investigators can implement meaningful and ethical projects to better address health disparities. © 2013.

  18. Foundations of Logistics and Supply Chain Research

    DEFF Research Database (Denmark)

    Georgi, Christoph; Darkow, Inga-Lena; Kotzab, Herbert

    2013-01-01

    The purpose of this paper is to explore the current intellectual foundation of four leading academic journals within the field of logistics and supply chain management. We were interested to identify the most frequently quoted publications as well as their impact on logistics research. We examined...... 17,000 references of 412 papers and further analysed the 39 top-references with the means of multidimensional scaling (MDS), cluster- and factor analysis. We were able to identify a mix of textbooks and articles from academic journals and revealed a journal-specific citation pattern, not only...

  19. Foundations of intervention research in instrumental practice

    Directory of Open Access Journals (Sweden)

    Johannes Lunde Hatfield

    2016-01-01

    Full Text Available The goals of the present study are to evaluate, implement, and adapt psychological skills used in the realm of sports into music performance. This research project also aims to build foundations on how to implement future interventions to guide music students on how to optimize practice toward performance. A two-month psychological skills intervention was provided to two students from the national music academy’s bachelor program in music performance to better understand how to adapt and construct psychological skills training programs for performing music students. The program evaluated multiple intervention tools including the use of questionnaires, performance profiling, iPads, electronic practice logs, recording the perceived value of individual and combined work, as well as the effectiveness of different communication forms. Perceived effects of the intervention were collected through semi-structured interviews, observations, and logs.

  20. Netherlands Energy Research Foundation Annual Report 1987

    International Nuclear Information System (INIS)

    1988-06-01

    This Annual Report includes a brief survey of the nuclear research activities of the Netherlands Energy Research Center (ECN) in Petten during 1987. They cover the following subjects: reactor safety, processing, storage and disposal of radioactive waste, advanced nuclear reactors, radiation protection, nuclear analysis, and contributions to the European thermonuclear-fusion research. (H.W.). 20 figs.; 18 fotos; 1 tab

  1. Framework for systems engineering research

    CSIR Research Space (South Africa)

    Erasmus, L

    2013-08-01

    Full Text Available In this paper a framework is proposed to perform systems engineering research within South Africa. It is proposed that within the reference of the National Research Foundation (NRF) classification of research, systems engineering is a Field...

  2. Case Study Research: Foundations and Methodological Orientations

    Directory of Open Access Journals (Sweden)

    Helena Harrison

    2017-01-01

    Full Text Available Over the last forty years, case study research has undergone substantial methodological development. This evolution has resulted in a pragmatic, flexible research approach, capable of providing comprehensive in-depth understanding of a diverse range of issues across a number of disciplines. Change and progress have stemmed from parallel influences of historical transformations in approaches to research and individual researcher's preferences, perspectives, and interpretations of this design. Researchers who have contributed to the development of case study research come from diverse disciplines with different philosophical perspectives, resulting in a variety of definitions and approaches. For the researcher new to using case study, such variety can create a confusing platform for its application. In this article, we explore the evolution of case study research, discuss methodological variations, and summarize key elements with the aim of providing guidance on the available options for researchers wanting to use case study in their work. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1701195

  3. Qualitative Research in Counseling Psychology: Conceptual Foundations

    Science.gov (United States)

    Morrow, Susan L.

    2007-01-01

    Beginning with calls for methodological diversity in counseling psychology, this article addresses the history and current state of qualitative research in counseling psychology. It identifies the historical and disciplinary origins as well as basic assumptions and underpinnings of qualitative research in general, as well as within counseling…

  4. Content Analysis as a Foundation for Programmatic Research in Communication

    OpenAIRE

    Slater, Michael D.

    2013-01-01

    Previous arguments that content analyses provide the descriptive foundation for media effects research (McLeod & Reeves, 1980) are extended to include that content analyses can provide a sound and useful foundation for programmatic research by individual communication scientists. I discuss examples from my own work and from that of colleagues in communication and related disciplines. Use of messages sampled and coded in a content analysis in combination with survey data sets or as stimuli in ...

  5. Research award: Foundations for Innovation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... strengthen science, technology, engineering, and mathematics (STEM) skills ... What are barriers and enablers to academia/industry research collaborations for ... Prior field experience in a developing country will be considered an asset.

  6. Progeria Research Foundation Diagnostic Testing Program

    Science.gov (United States)

    ... Share the DVD Meet the Kids in the Movie Bring LATS to the classroom! Close News/Events ... this could severely affect their research results and interpretation. Through the PRF Diagnostics Program, each cell line ...

  7. Ontological and Epistemological Foundations of Qualitative Research

    Directory of Open Access Journals (Sweden)

    Irene Vasilachis de Gialdino

    2009-05-01

    Full Text Available The purpose of this paper is to describe the most relevant features of qualitative research in order to show how, from the Epistemology of the Known Subject perspective I propose, it is necessary to review first the ontological and then the epistemological grounds of this type of inquiry. I begin by following the path that leads from the Epistemology of the Knowing Subject to the Epistemology of the Known Subject, proposed as a new and non exclusive way of knowing. I pass on to describe the primary and secondary characteristics of qualitative research, expressing the need for an ontological rupture. Finally, cognitive interaction and cooperative knowledge construction are considered as two fundamental features in the process of qualitative research grounded on the Epistemology of the Known Subject. URN: urn:nbn:de:0114-fqs0902307

  8. MS Swaminathan Research Foundation : Organizational and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... carried out under project 105276. Building on the results of the assessment, this grant will provide core support to MSSRF's Coastal systems research and strategic planning, and promote synergies across programs through internal learning, particularly in the areas of knowledge management, networking and evaluation.

  9. The principle of an NRF rating system for the humanities and social ...

    African Journals Online (AJOL)

    The National Research Foundation (NRF) is proposing to introduce a ratings system for the humanities and social sciences comparable to that which pertains in the natural sciences. The article welcomes this development, and argues for full and open consultation with the research community regarding appropriate ratings ...

  10. Foundational principles of classical Ayurveda research

    Directory of Open Access Journals (Sweden)

    Somik Raha

    2013-01-01

    Full Text Available Double-blind randomized controlled trials (RCTs are viewed as the golden standard of drug research in Western medicine. However, RCTs are far from "golden" in many respects. They are impractical for many therapies, such as for surgeries and complex lifestyle changes. They encourage a one-size-fits-all approach to medical treatment that fails to address the huge diversity among individual patients in terms of their physical and emotional symptoms, social and cultural upbringing, and other factors. Perhaps, more importantly, they do not help doctors make the best medical decisions required to produce optimal patient outcomes. To guide a search for an alternate model of medical research, three principles based on Ayurveda, an ancient and powerful system of health care that has stood the test of time, are presented. These principles, arrived at after mining Ayurvedic epistemology, are: Inductive learning, whole systems thinking, and individually optimized therapy. In honor of the ancient sages or "Rishis," whose voice is used to deliver Ayurvedic knowledge in the ancient texts of Ayurveda, these are referred to as the "Rishi principles." Individually optimized therapy is interpreted using the lens of decision analysis. Common research methodologies are examined for embodiment of these principles.

  11. Ontological and epistemological foundations of qualitative research

    OpenAIRE

    Vasilachis, Irene

    2016-01-01

    The purpose of this paper is to describe the most relevant features of qualitative research in order to show how, from the Epistemology of the Known Subject perspective I propose, it is necessary to review first the ontological and then the epistemological grounds of this type of inquiry. I begin by following the path that leads from the Epistemology of the Knowing Subject to the Epistemology of the Known Subject, proposed as a new and non exclusive way of knowing. I pass on to describe the p...

  12. Annual report 1987 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Eggen, H.; Benschop, H.; Ebbing, G.

    1988-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of yound physicists. The research groups are classified in eight socalled research communities: nuclear physics, atomic physics, metals, semiconductors, solid state, thermonuclear research and plasma physics, theoretical high-energy physics. This annual report accounts for the management, financial and personnel affairs, and professional/organizational reports of the aforementioned research communities and corresponding research groups. (H.W.). refs.; figs.; tabs

  13. Content Analysis as a Foundation for Programmatic Research in Communication.

    Science.gov (United States)

    Slater, Michael D

    2013-06-01

    Previous arguments that content analyses provide the descriptive foundation for media effects research (McLeod & Reeves, 1980) are extended to include that content analyses can provide a sound and useful foundation for programmatic research by individual communication scientists. I discuss examples from my own work and from that of colleagues in communication and related disciplines. Use of messages sampled and coded in a content analysis in combination with survey data sets or as stimuli in experiments are highlighted. The particular potential for employing larger numbers of randomly sampled messages in experimental designs, and, with use of appropriate statistical methods, being able to generalize to populations of messages, is described.

  14. Expanding the Foundation: Climate Change and Opportunities for Educational Research

    Science.gov (United States)

    Henderson, Joseph; Long, David; Berger, Paul; Russell, Constance; Drewes, Andrea

    2017-01-01

    Human-caused climate change is a dominant global challenge. Unlike other disciplines and fields, there has as yet been only limited attention to climate change in educational research generally, and in educational foundations in particular. Education is key to assisting humanity in mitigating and adapting to climate change, and educational…

  15. Annual report'81 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Heijn, J.; Hooren, M.J.H. van

    1982-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of young physicists. The research groups are classified in eight so-called research communities: nuclear physics, atomic physics, metals, semiconductors, solid state, thermonuclear research and plasma physics, theoretic high-energy physics. Besides accounts of the management, financial and personnel affairs, and professional/organizational reports of the aforementioned research communities and corresponding research groups, this annual report presents a number of trend articles of which two are in INIS scope, entitled respectively: Non-perturbative methods in field theory; Balance between bulk and beam studies in atomic collision research. (H.W.) refs.; figs.; tabs

  16. Annual report '82 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Hooren, M.J.H. van; Miltenburg, J.W.

    1983-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of young physicists. The research groups are classified in eight so-called research communities: nuclear physics, atomic physics, metals, semiconductors, solid state, thermonuclear research and plasma physics, theoretic high-energy physics. Besides accounts of the management, financial and personnel affairs, and professional/organizationa reports of the aforementioned research communities and corresponding research groups, this annual report presents a number of trend articles one of them being in INIS scope, discusses some experiments with the 500 MeV electron accelerator MEA. (H.W.). refs.; figs.; tabs

  17. Annual report '85 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Eggen, J.J.H.; Hofman, E.A.E.; Zwaan, B.E. van der

    1986-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of young physicists. The research groups are classified in eight socalled research communities: nuclear physics, atomic physics, metals, semiconductors, solid state, thermonuclear research and plasma physics, theoretic high-energy physics. Besides accounts of the management, financial and personnel affairs, and professional/organizational reports of the aformentioned research communities and corresponding research groups, this annual report presents a number of trend articles one of which being in INIS scope, dealing with the evidence of non-nucleonic degrees of freedom in nuclei from 500 MeV electroscattering experiments at NIKHEF-K. (H.W.). refs.; figs.; tabs

  18. Annual report '84 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Hooren, M.J.H. van; Miltenburg, J.W.

    1984-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of young physicists. The research groups are classified in eight socalled research communities: nuclear physics, atomic physics, metals, semiconuctors, solid state, thermonuclear research and plasma physics, theoretic high-energy physics. Besides accounts of the management, financial and personnel affairs, and professional/organizational reports of the aforementioned research communities and corresponding research groups, this annual report presents a number of trend articles of which three are in INIS scope, respectively dealing with the experimental deiscovery of intermediate vector bosons at CERN, the study of macroscopic properties of nuclear matter by collision experiments of high-energetic nuclei, and how atoms can be made 'visible' by atomic-collision experiments. (H.W.). refs.; figs.; tabs

  19. Annual report '83 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Hooren, M.J.H. van; Miltenburg, J.W.

    1984-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of young physicists. The research groups are classified in eight so-called research communities: nuclear physics, atomic physics, metals, semiconductors, solid state, thermonuclear research and plasma physics, theoretic high-energy physics. Besides accounts of the management, financial and personnel affairs, and professional/organizational reports of the aforementioned research communities and corresponding research groups, this annual report presents a number of trend articles of which three are in INIS scope, respectively dealing with study of atomic collisions in electromagnetic-radiation fields, 3 He studies at extremely low temperatures, and a diagnostic system for measuring the electron temperature in a JET-plasma. (H.W.). refs.; figs.; tabs

  20. Annual report 1986 Foundation for fundamental research on matter

    International Nuclear Information System (INIS)

    Eggen, J.J.H.; Ebbing, G.E.G.

    1987-01-01

    The Dutch Foundation for Fundamental Research of Matter (FOM) makes it her aim to stimulate the fundamentally scientific research of matter in the Netherlands. She attempts to obtain this by coordinating of existing research projects and by involving her institutes and research groups in the education of young physicists. The research groups are classified in eight socalled research communities: nuclear physics, atomic physics, metals, semiconductors, solid state, thermonuclear research and plasma physics, theoretic high-energy physics. Besides accounts of the management, financial and personnel affairs, and professional/organizational reports of the aforementioned research communities and corresponding research groups, this annual report presents a number of trend articles of which one, treating superstring theory, is in INIS scope. (H.W.) refs.; figs.; tabs

  1. Nrf2: bane or blessing in cancer?

    Science.gov (United States)

    Xiang, MingJun; Namani, Akhileshwar; Wu, ShiJun; Wang, XiaoLi

    2014-08-01

    The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element pathway serves a major function in endogenous cytoprotection in normal cells. Nrf2 is a transcription factor that mainly regulates the expression of a wide array of genes that produce the antioxidants and other proteins responsible for the detoxification of xenobiotics and reactive oxygen species. Nrf2 mediates the chemoprevention of cancer in normal cells. Growing body of evidence suggests that Nrf2 is not only involved in the chemoprevention of normal cells but also promotes the growth of cancer cells. However, the mechanism underlying the function of Nrf2 in oncogenesis and tumor protection in cancer cells remains unclear and thus requires further study. This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs. This review also discusses the future challenges in Nrf2 research.

  2. Final Task Report on NRF Measurements of Photon Scattering Resonances in Plutonium at the High Voltage Research Laboratory of MIT

    International Nuclear Information System (INIS)

    Johnson, M S; McNabb, D P; Norman, E B

    2007-01-01

    Conclusions of this report are that there are 13 new transitions associated with NRF states in 239 Pu that have been discovered. These resonances are between 2- and 2.5-MeV relative to the ground state in 239 Pu. The strengths of most these resonances are between 15 and 20 eV b. This approximately is the strength required for using the transmission detection method for NRF [Pruet et al J. Appl. Phys. 99 12310 (2006)] for six-sigma alarm confidence levels. Future measurements on 239 Pu at higher photon energies are necessary to probe for NRF strengths at higher energies. Such resonances may be more advantageous to the NRF technique with FINDER if they are stronger or if the mean free path of these energetic photons is longer

  3. Intelligent Propulsion System Foundation Technology: Summary of Research

    Science.gov (United States)

    2008-01-01

    The purpose of this cooperative agreement was to develop a foundation of intelligent propulsion technologies for NASA and industry that will have an impact on safety, noise, emissions, and cost. These intelligent engine technologies included sensors, electronics, communications, control logic, actuators, smart materials and structures, and system studies. Furthermore, this cooperative agreement helped prepare future graduates to develop the revolutionary intelligent propulsion technologies that will be needed to ensure pre-eminence of the U.S. aerospace industry. This Propulsion 21 - Phase 11 program consisted of four primary research areas and associated work elements at Ohio universities: 1.0 Turbine Engine Prognostics, 2.0 Active Controls for Emissions and Noise Reduction, 3.0 Active Structural Controls and Performance, and 4.0 System Studies and Integration. Phase l, which was conducted during the period August 1, 2003, through September 30, 2004, has been reported separately.

  4. Research Data Reusability: Conceptual Foundations, Barriers and Enabling Technologies

    Directory of Open Access Journals (Sweden)

    Costantino Thanos

    2017-01-01

    Full Text Available High-throughput scientific instruments are generating massive amounts of data. Today, one of the main challenges faced by researchers is to make the best use of the world’s growing wealth of data. Data (reusability is becoming a distinct characteristic of modern scientific practice. By data (reusability, we mean the ease of using data for legitimate scientific research by one or more communities of research (consumer communities that is produced by other communities of research (producer communities. Data (reusability allows the reanalysis of evidence, reproduction and verification of results, minimizing duplication of effort, and building on the work of others. It has four main dimensions: policy, legal, economic and technological. The paper addresses the technological dimension of data reusability. The conceptual foundations of data reuse as well as the barriers that hamper data reuse are presented and discussed. The data publication process is proposed as a bridge between the data author and user and the relevant technologies enabling this process are presented.

  5. Space Weather Research at the National Science Foundation

    Science.gov (United States)

    Moretto, T.

    2015-12-01

    There is growing recognition that the space environment can have substantial, deleterious, impacts on society. Consequently, research enabling specification and forecasting of hazardous space effects has become of great importance and urgency. This research requires studying the entire Sun-Earth system to understand the coupling of regions all the way from the source of disturbances in the solar atmosphere to the Earth's upper atmosphere. The traditional, region-based structure of research programs in Solar and Space physics is ill suited to fully support the change in research directions that the problem of space weather dictates. On the observational side, dense, distributed networks of observations are required to capture the full large-scale dynamics of the space environment. However, the cost of implementing these is typically prohibitive, especially for measurements in space. Thus, by necessity, the implementation of such new capabilities needs to build on creative and unconventional solutions. A particularly powerful idea is the utilization of new developments in data engineering and informatics research (big data). These new technologies make it possible to build systems that can collect and process huge amounts of noisy and inaccurate data and extract from them useful information. The shift in emphasis towards system level science for geospace also necessitates the development of large-scale and multi-scale models. The development of large-scale models capable of capturing the global dynamics of the Earth's space environment requires investment in research team efforts that go beyond what can typically be funded under the traditional grants programs. This calls for effective interdisciplinary collaboration and efficient leveraging of resources both nationally and internationally. This presentation will provide an overview of current and planned initiatives, programs, and activities at the National Science Foundation pertaining to space weathe research.

  6. Activities and future plans of the radiation effects research foundation

    International Nuclear Information System (INIS)

    Nagataki, Shigenobu

    2000-01-01

    The Radiation Effects Research Foundation (RERF) was established in 1975 as a binational research foundation supported by Japan and the United States. It continues the work of the Atomic Bomb Casualty Commission (ABCC) which was established in 1974. ABCC-RERF studies focus on several fixed cohorts of survivors and their children: the Life Span Study (LSS) cohort (120,000 survivors); the In-Utero cohort (3,300 people born within 9 months of the bombings); the F 1 cohort (88,000 people born between mid-1946 and 1984), and the Adult Health Study (AHS) cohort (an ongoing clinical study of 17,000 LSS survivors and 1,100 people exposed in-utero). Epidemiological data have shown increased risks of leukemia and solid cancers by radiation exposure among the survivors. Excess leukemia risks, especially for children, were markedly elevated 5 to 10 years after exposure and have continued at reduced levels. Excess solid cancer rates became apparent within 10 years after exposure, increasing throughout life in rough proportion to background rates. For doses of interest in radiation protection excess leukemia risks exhibit an upward curving dose response pattern while the solid cancer excess appears to be linear by dose with no apparent threshold. In addition to malignancy, AHS data has shown dose-related increased risk for various non-malignant diseases; radiation cataracts, benign tumors of uterus, thyroid and parathyroid (hyperparathyroidism), and autoimmune thyroid diseases. Persons exposed in-utero exhibit a broad range of dose-related effects including delayed growth and development and higher rates of microcephaly. Studies of birth defects, chromosome aberrations, childhood mortality, and genetic variants of serum or erythrocyte proteins have provided no indication of heritable mutations in the F 1 cohort. Continued follow-up of survivors exposed as children (90% are still alive) is essential to understanding the temporal pattern of excess risks and lifetime risks, and may

  7. Self-Determination Theory as a Foundation for Personality Researchers.

    Science.gov (United States)

    Sheldon, Kennon M; Prentice, Mike

    2017-11-16

    In this introductory article we first describe the impetus for this special issue. What made us think that Self-Determination Theory (SDT) might provide a sort of foundation for the rest of personality psychology? For readers unfamiliar with SDT, we then provide a historical overview which covers the evolution of the six "mini-theories" that currently comprise SDT: cognitive evaluation theory, causality orientations theory, organismic integration theory, basic psychological needs theory, goal contents theory, and relational motivation theory. Following each section are preliminary suggestions about how each mini-theory might be useful or informative in other branches of personality. This special issue contains 9 articles, each of which makes its own attempt to newly link its area of personality research to SDT. Even if SDT is not the appropriate seed for greater consilience in personality psychology, we urge the field not to neglect the search for unifying principles (Sheldon, Chen, & Hilpert, 2011); it may finally be time to renew the search for a "grand theory" in personality. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  8. Radiation Effects Research Foundation bibliography of published papers, 1986

    International Nuclear Information System (INIS)

    1987-01-01

    The bibliography lists the titles of a total of 75 papers published by members of the Radiation Effects Research Foundation in 1986 (three of them published in 1985). The papers cover; 'The central nervous system and in utero exposure to ionizing radiation', 'Future directions for biostatistics and cancer epidemiology in Japan', 'Passive smoking and lung cancer among Japanese women', 'Late effects of atomic bomb radiation on human immune response', 'Delayed effects of atomic bomb radiation to human cellular immune competence', 'Characterization of three electrophoretic variants of human erythrocyte triosephosphate isomerase found in Japanese', 'A follow-up study of clonal T-lymphocytes with chromosome aberrations in Hiroshima A-bomb survivors', 'Comments on recent cytogenetic findings at RERF', 'Cytogenetic 'rogue' cells; What is their frequency, origin, and evolutionary sinificance?', 'A parallel analysis of cancer mortality among atomic bomb survivors and patients with ankylosing spondylitis given X-ray therapy', 'Cancer of the thyroid and salivary glands', 'Analysis of peripheral blood lymphocytes of atomic bomb survivors using monoclonal antibodies', 'Celluar immune competence of patients with lung cancer and other lung diseases. I. Analysis of peripheral blood lymphocyte subsets using monoclonal antibodies', etc. (N.K.) 75 refs

  9. Radiation Effects Research Foundation bibliography of published papers, 1987

    International Nuclear Information System (INIS)

    1988-08-01

    The report lists the titles and authors of the reports of studies made under the Radiation Effects Research Foundation. The list include 87 studies, which cover 'immunological diagnosis of lung cancer', 'electrophoretic variants of haptoglobin found in the children of atomic bomb survivors', 'rogue cells in the general human population', 'host variation of X-ray sensitivity among atomic bomb survivors with or without breast cancer', 'disorders in the endocrine gland and gonad of A-bomb survivors', 'incidence of vertebral compression fractures among atomic bomb survivors', 'measurement of the frequency of in vivo somatic mutation in atomic bomb survivors by T-cell cloning', 'mechanism of carcinogenesis in A-bomb survivors', 'effects of aging on blood pressure', 'expediting factors of blood sedimentation of heavily exposed survivors', 'record linkage between local cancer registry and tumor and tissue registries', 'reclassification of diagnosis and types of leukemia in atomic bomb survivors in Hiroshima', 'cytogenetic study in utero exposed individuals', 'estimation of indoor and outdoor A-bomb gamma-ray doses by thermoluminescence measurement', and many other studies. (N.K.) 87 refs

  10. Environmental Science and Research Foundation, Inc. annual technical report: Calendar year 1997

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, R.D.; Warren, R.W. [eds.

    1998-05-01

    This Annual Technical Report describes work conducted for the Department of Energy, Idaho Operations Office (DOE-ID), by the Environmental Science and Research Foundation (Foundation). The Foundation`s mission to DOE-ID provides support in several key areas. The Foundation conducts an environmental monitoring and surveillance program over an area covering much of the upper Snake River Plain, and provides environmental education and support services related to Idaho National Engineering and Environmental Laboratory (INEEL) natural resource issues. Also, the Foundation, with its University Affiliates, conducts ecological and radioecological research on the Idaho National Environmental Research Park. This research benefits major DOE-ID programs including Waste Management, Environmental Restoration, Spent Nuclear Fuels, and Land Management Issues. Summaries are included of the individual research projects.

  11. The impact of kidney foundations in alleviating the burden of CKD in India - an example, Tamilnad Kidney Research Foundation.

    Science.gov (United States)

    Abraham, Georgi; Vijayan, Madhusudan; Ravi, Rajalakshmi; Kumaraswami, Latha; Venkatesan, Malathy

    Chronic kidney disease (CKD) is a major public health problem in India. The CKD registry of India has been formed to understand the epidemiology of CKD in India. Due to health economics in India, the majority of CKD-affected patients cannot afford renal replacement therapy (RRT) services. There is an unmet need to improve the awareness of kidney disease in India, and the focus should be on prevention and early detection of CKD by screening high risk populations. The Tamilnad Kidney Research (TANKER) Foundation is a charitable trust established in 1993 with the aim to improve awareness and provide quality affordable treatment to underprivileged patients. TANKER is supported by contributions from well-wishers. It has three arms: i) treatment arm, ii) research arm, and iii) awareness and screening arm. TANKER Foundation offers free and subsidized dialysis twice weekly to 227 underprivileged patients. TANKER dialysis has been supported by state government funding schemes. TANKER actively supports and conducts research in nephrology. More than 100,000 people have benefitted from TANKER's kidney awareness programs. The screening programs have provided for early detection of CKD in both urban and rural areas. TANKER award functions are held annually to recognize research and exemplary service to society. The TANKER Foundation can be used as a model for developing countries to address the unmet needs in CKD management.

  12. Environmental Science and Research Foundation annual technical report: Calendar year 1996

    Energy Technology Data Exchange (ETDEWEB)

    Morris, R.C.; Blew, R.D. [eds.

    1997-07-01

    This Annual Technical Report describes work conducted for the Department of Energy, Idaho Operations Office (DOE-ID), by the Environmental Science and Research Foundation (Foundation). The Foundation`s mission to DOE-ID provides support in several key areas. The authors conduct an environmental monitoring and surveillance program over an area covering much of the upper Snake River Plain, and provide environmental education and support services related to Idaho National Engineering and Environmental Laboratory (INEEL) natural resource issues. Also, the Foundation, with its University Affiliates, conducts ecological and radioecological research in the Idaho National Environmental Research Park. This research benefits major DOE-ID programs including Waste Management, Environmental Restoration, Spent Nuclear Fuels, and Land Management Issues. The major accomplishments of the Foundation and its University Affiliates during the calendar year 1996 are discussed.

  13. Smart Contract Templates: foundations, design landscape and research directions

    OpenAIRE

    Clack, Christopher D.; Bakshi, Vikram A.; Braine, Lee

    2016-01-01

    In this position paper, we consider some foundational topics regarding smart contracts (such as terminology, automation, enforceability, and semantics) and define a smart contract as an automatable and enforceable agreement. We explore a simple semantic framework for smart contracts, covering both operational and non-operational aspects, and describe templates and agreements for legally-enforceable smart contracts, based on legal documents. Building upon the Ricardian Contract, we identify op...

  14. State University of New York Research Foundation: Controls over Direct Costs. Report 93-S-64.

    Science.gov (United States)

    New York State Office of the Comptroller, Albany. Div. of Management Audit.

    An evaluation was done of the State University of New York (SUNY) Research Foundation's controls over direct expenditures for research and sponsored activities. The Foundation is a private, non-profit educational corporation established to expand the educational mission of SUNY through fund raising, administration of gifts and grants, and…

  15. Environmental Science and Research Foundation, Inc. annual technical report: Calendar year 1997

    International Nuclear Information System (INIS)

    Reynolds, R.D.; Warren, R.W.

    1998-05-01

    This Annual Technical Report describes work conducted for the Department of Energy, Idaho Operations Office (DOE-ID), by the Environmental Science and Research Foundation (Foundation). The Foundation's mission to DOE-ID provides support in several key areas. The Foundation conducts an environmental monitoring and surveillance program over an area covering much of the upper Snake River Plain, and provides environmental education and support services related to Idaho National Engineering and Environmental Laboratory (INEEL) natural resource issues. Also, the Foundation, with its University Affiliates, conducts ecological and radioecological research on the Idaho National Environmental Research Park. This research benefits major DOE-ID programs including Waste Management, Environmental Restoration, Spent Nuclear Fuels, and Land Management Issues. Summaries are included of the individual research projects

  16. Research on the Teaching System of the University Computer Foundation

    Directory of Open Access Journals (Sweden)

    Ji Xiaoyun

    2016-01-01

    Full Text Available Inonal students, the teaching contents, classification, hierarchical teaching methods with the combination of professional level training, as well as for top-notch students after class to promote comprehensive training methods for different students, establish online Q & A, test platform, to strengthen the integration professional education and computer education and training system of college computer basic course of study and exploration, and the popularization and application of the basic programming course, promote the cultivation of university students in the computer foundation, thinking methods and innovative practice ability, achieve the goal of individualized educ the College of computer basic course teaching, the specific circumstances of the need for students, professiation.

  17. Environmental Science and Research Foundation annual technical report: Calendar year 1996

    International Nuclear Information System (INIS)

    Morris, R.C.; Blew, R.D.

    1997-01-01

    This Annual Technical Report describes work conducted for the Department of Energy, Idaho Operations Office (DOE-ID), by the Environmental Science and Research Foundation (Foundation). The Foundation's mission to DOE-ID provides support in several key areas. The authors conduct an environmental monitoring and surveillance program over an area covering much of the upper Snake River Plain, and provide environmental education and support services related to Idaho National Engineering and Environmental Laboratory (INEEL) natural resource issues. Also, the Foundation, with its University Affiliates, conducts ecological and radioecological research in the Idaho National Environmental Research Park. This research benefits major DOE-ID programs including Waste Management, Environmental Restoration, Spent Nuclear Fuels, and Land Management Issues. The major accomplishments of the Foundation and its University Affiliates during the calendar year 1996 are discussed

  18. NRF TRIGA packaging

    International Nuclear Information System (INIS)

    Clements, M.D.

    1995-11-01

    Training Reactor Isotopes, General Atomics (TRIGA reg-sign) Reactors are in use at four US Department of Energy (DOE) complex facilities and at least 23 university, commercial, or government facilities. The development of the Neutron Radiography Facility (NRF) TRIGA packaging system began in October 1993. The Hanford Site NRF is being shut down and requires an operationally user-friendly transportation and storage packaging system for removal of the TRIGA fuel elements. The NRF TRIGA packaging system is designed to remotely remove the fuel from the reactor and transport the fuel to interim storage (up to 50 years) on the Hanford Site. The packaging system consists of a cask and an overpack. The overpack is used only for transport and is not necessary for storage. Based upon the cask's small size and light weight, small TRIGA reactors will find it versatile for numerous refueling and fuel storage needs. The NRF TRIGA packaging design also provides the basis for developing a certifiable and economical packaging system for other TRIGA reactor facilities. The small size of the NRF TRIGA cask also accommodates placing the cask into a larger certified packaging for offsite transport. The Westinghouse Hanford Company NRF TRIGA packaging, as described herein can serve other DOE sites for their onsite use, and the design can be adapted to serve university reactor facilities, handling a variety of fuel payloads

  19. Radiation Effects Research Foundation bibliography of published papers, 1989

    International Nuclear Information System (INIS)

    1990-01-01

    This issue is the bibliography of the publication by the staffs of the Radiation Effects Research Institute (RERF) in 1989. Titles in original and English language with author names are enumerated. Indexes by research areas and by author name are also attached. (J.P.N.) 62 refs

  20. Research within the disciplines foundations for reference and library instruction

    CERN Document Server

    Keeran, Peggy

    2014-01-01

    Research within the Disciplines is designed to help reference librarians - and students studying to become librarians - gain that deeper understanding of disciplinary differences that allows them to comfortably solve information needs rather than merely responding to questions, and practical knowledge about how to work with researchers in a library setting.

  1. Radiation Effects Research Foundation bibliography of published papers, 1988

    International Nuclear Information System (INIS)

    1989-01-01

    This issue is the bibliography of the publication by the staffs of the Radiation Effects Research Institute (RERF) in 1988. Titles in original and English language with author names are enumerated. Indeces by research areas and by author name are also attached. (J.P.N.) 99 refs

  2. Environmental Science and Research Foundation. Annual technical report, April 11, 1994--December 31, 1994

    International Nuclear Information System (INIS)

    Reynolds, T.D.; Morris, R.C.; Markham, O.D.

    1995-06-01

    This Annual Technical Report describes work conducted for the Department of Energy, Idaho Operations Office, by the Environmental Science and Research Foundation (Foundation) for work under contract DE-AC07-94ID13268. The Foundation began, on April 11, 1994, to conduct environmental surveillance near to and distant from the Idaho National Engineering Laboratory, provide environmental public relations and education related to INEL natural resource issues, and conduct ecological and radioecological research benefiting major DOE-ID programs including Waste Management, Environmental Restoration, Spent Nuclear Fuels, and Infrastructure

  3. Environmental Science and Research Foundation. Annual technical report, April 11, 1994--December 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, T.D.; Morris, R.C.; Markham, O.D. [eds.

    1995-06-01

    This Annual Technical Report describes work conducted for the Department of Energy, Idaho Operations Office, by the Environmental Science and Research Foundation (Foundation) for work under contract DE-AC07-94ID13268. The Foundation began, on April 11, 1994, to conduct environmental surveillance near to and distant from the Idaho National Engineering Laboratory, provide environmental public relations and education related to INEL natural resource issues, and conduct ecological and radioecological research benefiting major DOE-ID programs including Waste Management, Environmental Restoration, Spent Nuclear Fuels, and Infrastructure.

  4. Establishing a research agenda for Foundation Phasei initial ...

    African Journals Online (AJOL)

    USER

    2016-08-19

    Aug 19, 2016 ... This paper profiles empirical research relating to initial ... post-1994 democratic government chose to locate all initial teacher education in higher education institutions .... philosophical aspects of teacher education, issues.

  5. Soutien institutionnel à l'Economic and Social Research Foundation ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Driving vaccine innovations to improve lives and livelihoods. Five world-class research teams are working to develop vaccines for neglected livestock diseases in the Global South. View moreDriving vaccine innovations to improve lives and livelihoods ...

  6. Afterword: returning to philosophical foundations in research ethics.

    Science.gov (United States)

    Eyal, Nir

    2017-02-01

    This is an afterword to the JME symposium on the benefit/risk ratio challenge in clinical research, and the case of HIV cure. It notes implications of the symposium for research ethics in general. 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/.

  7. Annual report of Radiation Effects Research Foundation, April 1, 1988 - March 31, 1989

    International Nuclear Information System (INIS)

    1990-01-01

    This annual report summarizes the research activities of the Radiation Effects Research Foundation in the fiscal year 1988. Outcome of the work is presented, covering the two major workshops for 'immunology' and for 'radiation-induced carcinogenesis' which were held in Hiroshima on November 28-29, 1988, and on March 16-18, 1989, respectively. Study meeting of 'medical radiation research program' and Japan-the U.S. joint meeting of 'DS 86' are reported, as well as the other scientific lectures and campus study seminars. Included are research abstracts published by the Research Foundation staff. The bibliography of papers, published in scientific journals and presented in scientific meetings, is provided. Appendices give the details of the aforementioned workshops, the continuing research issues, and the personnel list of the Radiation Effects Research Foundation. (N.K.)

  8. Laying the Foundations for Scientometric Research: A Data Science Approach

    Science.gov (United States)

    Perron, Brian E.; Victor, Bryan G.; Hodge, David R.; Salas-Wright, Christopher P.; Vaughn, Michael G.; Taylor, Robert Joseph

    2017-01-01

    Objective: Scientometric studies of social work have stagnated due to problems with the organization and structure of the disciplinary literature. This study utilized data science to produce a set of research tools to overcome these methodological challenges. Method: We constructed a comprehensive list of social work journals for a 25-year time…

  9. PRO development: rigorous qualitative research as the crucial foundation

    OpenAIRE

    Lasch, Kathryn Eilene; Marquis, Patrick; Vigneux, Marc; Abetz, Linda; Arnould, Benoit; Bayliss, Martha; Crawford, Bruce; Rosa, Kathleen

    2010-01-01

    Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented ...

  10. Disparate foundations of scientists' policy positions on contentious biomedical research.

    Science.gov (United States)

    Edelmann, Achim; Moody, James; Light, Ryan

    2017-06-13

    What drives scientists' position taking on matters where empirical answers are unavailable or contradictory? We examined the contentious debate on whether to limit experiments involving the creation of potentially pandemic pathogens. Hundreds of scientists, including Nobel laureates, have signed petitions on the debate, providing unique insights into how scientists take a public stand on important scientific policies. Using 19,257 papers published by participants, we reconstructed their collaboration networks and research specializations. Although we found significant peer associations overall, those opposing "gain-of-function" research are more sensitive to peers than are proponents. Conversely, specializing in fields directly related to gain-of-function research (immunology, virology) predicts public support better than specializing in fields related to potential pathogenic risks (such as public health) predicts opposition. These findings suggest that different social processes might drive support compared with opposition. Supporters are embedded in a tight-knit scholarly community that is likely both more familiar with and trusting of the relevant risk mitigation practices. Opponents, on the other hand, are embedded in a looser federation of widely varying academic specializations with cognate knowledge of disease and epidemics that seems to draw more heavily on peers. Understanding how scientists' social embeddedness shapes the policy actions they take is important for helping sides interpret each other's position accurately, avoiding echo-chamber effects, and protecting the role of scientific expertise in social policy.

  11. Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin

    Science.gov (United States)

    Rojo de la Vega, Montserrat; Zhang, Donna D.; Wondrak, Georg T.

    2018-01-01

    Environmental exposure to solar ultraviolet (UV) radiation causes acute photodamage, premature aging, and skin cancer, attributable to UV-induced genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2 [nuclear factor erythroid 2 (E2)-related factor 2] is the master regulator of the cellular antioxidant response protecting skin against various environmental stressors including UV radiation and electrophilic pollutants. NRF2 in epidermal keratinocytes can be activated using natural chemopreventive compounds such as the apocarotenoid bixin, an FDA-approved food additive and cosmetic ingredient from the seeds of the achiote tree (Bixa orellana). Here, we tested the feasibility of topical use of bixin for NRF2-dependent skin photoprotection in two genetically modified mouse models [SKH1 and C57BL/6J (Nrf2+/+ versus Nrf2-/-)]. First, we observed that a bixin formulation optimized for topical NRF2 activation suppresses acute UV-induced photodamage in Nrf2+/+ but not Nrf2-/- SKH1 mice, a photoprotective effect indicated by reduced epidermal hyperproliferation and oxidative DNA damage. Secondly, it was demonstrated that topical bixin suppresses PUVA (psoralen + UVA)-induced hair graying in Nrf2+/+ but not Nrf2-/- C57BL/6J mice. Collectively, this research provides the first in vivo evidence that topical application of bixin can protect against UV-induced photodamage and PUVA-induced loss of hair pigmentation through NRF2 activation. Topical NRF2 activation using bixin may represent a novel strategy for human skin photoprotection, potentially complementing conventional sunscreen-based approaches. PMID:29636694

  12. Annual report of Radiation Effects Research Foundation, April 1, 1989 - March 31, 1990

    International Nuclear Information System (INIS)

    1991-01-01

    This annual report summarizes the research activities of the Radiation Effects Research Foundation in the fiscal year, 1989. Outcome of the work is presented, covering epidemiology, Adult Health Survey Program, cytogenetics, genetic biochemical survey, immunology, cytobiology, and statistics. Symposium entitled 'update information on effects of radiation', held on October 8, 1989, and the final workshop on 'aging', held on March 29-31, 1990, are outlined, accompanied by the other scientific lectures and campus study seminars. The report also includes research abstracts published by the Research Foundation staff. Bibliography of papers, published in scientific journals and presented in scientific meetings, is provided. Appendices give the proceedings of the aforementioned workshop on 'aging', the continuing research issues, and the personal list of the Radiation Effects Research Foundation. (N.K.)

  13. Age-related retinopathy in NRF2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    2011-04-01

    Full Text Available Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms.Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice.Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

  14. PRO development: rigorous qualitative research as the crucial foundation.

    Science.gov (United States)

    Lasch, Kathryn Eilene; Marquis, Patrick; Vigneux, Marc; Abetz, Linda; Arnould, Benoit; Bayliss, Martha; Crawford, Bruce; Rosa, Kathleen

    2010-10-01

    Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity.

  15. Notification: Evaluation of EPA’s Use of Other Federal Agencies, Universities and Foundations for Research

    Science.gov (United States)

    Project #OPE-FY14-0048, September 19, 2014. The OIG plans to begin preliminary research on the EPA's use of other federal agencies, universities and foundations for agency research in the Office of Research and Development (ORD) on October 14, 2014.

  16. Post-Foundational Discourse Analysis: A Suggestion for a Research Program

    Directory of Open Access Journals (Sweden)

    Tomas Marttila

    2015-08-01

    Full Text Available Post-foundational discourse analysis, also labeled as Essex School in Discourse Analysis, has been observed to suffer from a considerable methodological deficit that limits its applicability in empirical research. The principal aim of this article is to overcome this methodological deficit by constructing the research program of the post-foundational discourse analysis that facilitates its operationalization in empirical research. In accordance with Imre LAKATOS (1970 and David HOWARTH (2004a, a research program is referred to an internally consistent and openly scrutinizable system of theoretical, methodological and phenomenal concepts that opens up the possibility to distinguish between the "negative" and the "positive" heuristics of empirical research. The first three sections develop the positive heuristics of the post-foundational discourse analysis by elucidating its theoretical foundations, methodological position and phenomenal framework. The concluding fourth section draws on the presented positive heuristics to outline the analytical stages and strategies of the post-foundational discourse analysis and discusses suitable methods for sampling and interpreting empirical data. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs150319

  17. Private Philanthropy and Basic Research in Mid-Twentieth Century America: The Hickrill Chemical Research Foundation.

    Science.gov (United States)

    Gortler, Leon; Weininger, Stephen J

    2017-02-01

    The Hickrill Chemical Research Foundation, located north of New York City on the estate of its patrons, Sylvan and Ruth Alice Norman Weil, had a short (1948-59) but productive life. Ruth Alice Weil received a Ph.D. in organic chemistry in 1947, directed by William von Eggers Doering of Columbia University. She intended that Hickrill contribute to cancer chemotherapy while providing resources for Doering's more speculative research. Ultimately, Doering's commitment to theoretical organic chemistry set Hickrill's research agenda. Lawrence Knox, an African American with a Harvard Ph.D., supervised the laboratory's daily activities. Hickrill's two dozen postdoctoral fellows produced path-breaking results in Hückel aromatic theory and reactive intermediate chemistry, fostering the postwar emphasis on "basic science." This essay places the Laboratory's successes in the wider context of postwar politics and scientific priorities. Private philanthropic support of basic science arose because it received little pre-World War II government support. In the immediate postwar period, modest organisations like Hickrill still met a need, but the increasing governmental defence- and non-defence-related support for science eventually rendered them unnecessary.

  18. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    International Nuclear Information System (INIS)

    Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

    2011-01-01

    Research highlights: → Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. → HDAC inhibition decreases Nrf2 protein stability. → HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. → HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H 2 O 2 ) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H 2 O 2 -induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  19. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, Nicolas [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Thimmulappa, Rajesh [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E. [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Ito, Kazuhiro [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Barnes, Peter J., E-mail: p.j.barnes@imperial.ac.uk [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom)

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  20. Connecting Creativity Research and Practice in Art Education: Foundations, Pedagogies, and Contemporary Issues

    Science.gov (United States)

    Bastos, Flávia, Ed.; Zimmerman, Enid, Ed.

    2015-01-01

    In three broad sections--Foundations, Pedagogies, and Contemporary Issues--the editors and chapter authors of "Connecting Creativity Research and Practice in Art Education" articulate the significance of reconsidering creativity as a crucial dimension of art education research and practice today. This book represents a groundbreaking…

  1. Promising and Established Investigators' Experiences Participating in the National Athletic Trainers' Association Foundation Research Mentor Program.

    Science.gov (United States)

    Nottingham, Sara L; Mazerolle, Stephanie M; Barrett, Jessica L

    2017-04-01

      Mentorship is a helpful resource for individuals who transition from doctoral student to tenure-track faculty member. The National Athletic Trainers' Association (NATA) Research & Education Foundation offers a Research Mentor Program to provide mentorship to promising investigators, particularly as they work to establish independent lines of research.   To gain the perspectives of promising and established investigators on their participation in the NATA Foundation Research Mentor Program.   Qualitative, phenomenological research.   Higher education institutions.   Seven promising investigators (5 women, 2 men) and 7 established investigators (2 women, 5 men), all of whom had completed the NATA Foundation Research Mentor Program. Data Collection and Analysis We developed and piloted intervi: ew guides designed to gain participants' perspectives on their experiences participating in the NATA Foundation Research Mentor Program. Semistructured telephone interviews were completed with each individual and transcribed verbatim. Data were analyzed using a phenomenological approach, and saturation was obtained. Trustworthiness was established with the use of member checking, multiple-analyst triangulation, and data-source triangulation.   Three themes emerged from the interviews: (1) motivation, (2) collaboration, and (3) resources. Participants were motivated to become involved because they saw the value of mentorship, and mentees desired guidance in their research. Participants believed that collaboration on a project contributed to a positive relationship, and they also desired additional program and professional resources to support novice faculty.   Promising and established investigators should be encouraged to engage in mentoring relationships to facilitate mentees' research agendas and professional development. The NATA Foundation and athletic training profession may consider providing additional resources for novice faculty, such as training on

  2. Bibliometric analyses of publications from Centres of Excellence funded by the Danish National Research Foundation

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg; Costas, Rodrigo; Henriksen, Dorte

    2013-01-01

    research. The main focus of the evaluation is on the Centre of Excellence (CoE) scheme and the impact it has had on the Danish research system. The key topics addressed are the role of the DNRF in the Danish research funding system, research quality, research training and recruitment, internationalisation......, the interaction with host institutions, and the governance and management of the DNRF. The evaluation concludes that the DNRF has had a very positive impact on the quality of research in Denmark and recommends that the foundation is re-funded. The evaluation is based on a bibliometric study, self......-assessment report by DNRF, numerous interviews and desk studies. Appendix 5: Bibliometric analyses of publications from Centres of Excellence funded by the Danish National Research Foundation...

  3. Educators' Use of Research and Other Evidence within Local Grant Foundation Applications

    Science.gov (United States)

    Malin, Joel R.

    2016-01-01

    In this study, educators' requests for foundation grant funding to purchase desired educational materials or services were examined. Specifically, this study sought to review to what extent, and in what manner, educators utilize research and other forms of evidence to support their decision making. Data analysis revealed several themes. Although…

  4. Pre-Service Elementary Mathematics Teachers' Metaphors on Scientific Research and Foundations of Their Perceptions

    Science.gov (United States)

    Bas, Fatih

    2016-01-01

    In this study, it is aimed to investigate pre-service elementary mathematics teachers' perceptions about scientific research with metaphor analysis and determine the foundations of these perceptions. This phenomenological study was conducted with 182 participants. The data were collected with two open-ended survey forms formed for investigating…

  5. RECOMMENDED FOUNDATION FILL MATERIALS CONSTRUCTION STANDARD OF THE FLORIDA RADON RESEARCH PROGRAM

    Science.gov (United States)

    The report summarizes the technical basis for a recommended foundation fill materials standard for new construction houses in Florida. he radon-control construction standard was developed by the Florida Radon Research Program (FRRP). ill material standards are formulated for: (1)...

  6. INSTRUMENTS OF SUPPORT FOR RESEARCH AND DEVELOPMENT FUNDED BY LEADING DOMESTIC AND INTERNATIONAL SCIENCE FOUNDATIONS

    Directory of Open Access Journals (Sweden)

    Irina E. Ilina

    2017-06-01

    Full Text Available Introduction: one of the key aspects of the knowledge economy development is the growing significance of the results of research and development. The education and basic research play a key role in this process. Funding for education and fundamental science is carried out mainly at the expense of the state resources, including a system of foundations for scientific, engineering and innovation activities in Russia. The purpose of this article is to present recommendations for improving the tools of domestic foundations in funding fundamental research and development, including education and training. The propositions are made with a comparative analysis of the domestic and foreign science foun dations’ activities. Materials and Methods: the authors used analysis, comparison, induction, deduction, graphical analysis, generalisation and other scientific methods during the study. Results: the lack of comparability between domestic and foreign scientific funds in the volume of funding allocated for basic research and development is revealed. This situation affects the scientific research. The foreign foundations have a wide range of instruments to support research projects at all stages of the life cycle of grants for education and training prior to release of an innovative product to market (the use of “innovation elevator” system. The Russian national scientific foundations have no such possibilities. The authors guess that the Russian organisations ignore some of the instruments for supporting research and development. Use of these tools could enhance the effectiveness of research projects. According to the study of domestic and foreign experience in supporting research and development, the authors proposed a matrix composed of instruments for support in the fields of basic scientific researches and education with such phases of the project life cycle as “research” and “development”. Discussion and Conclusions: the foreign science

  7. Building a Bright Future. The Hydro Research Foundation's Fellowship Program

    Energy Technology Data Exchange (ETDEWEB)

    Vaughn, Brenna [Hydro Research Foundation, Inc., Evergreen, CO (United States); Linke, Deborah M. [Hydro Research Foundation, Inc., Evergreen, CO (United States)

    2015-12-29

    The Hydro Fellowship Program (program) began as an experiment to discover whether the hydropower industry could find mechanisms to attract new entrants through conducting relevant research to benefit the industry. This nationwide, new-to-the-world program was started through funding from the Wind and Water Power Technologies Office of the Energy Efficiency and Renewable Energy (EERE) Office of the Department of Energy (DOE). Between 2010-2015, the Hydro Research Foundation (HRF) designed and implemented a program to conduct valuable research and attract new entrants to the hydro workforce. This historic grant has empowered and engaged industry members from 25 organizations by working with 91 students and advisors at 24 universities in 19 states. The work funded answered pressing research needs in the fields of civil, mechanical, environmental, and electrical engineering, as well as law, energy engineering and materials innovation. In terms of number of individuals touched through funding, 148 individuals were supported by this work through direct research, mentorship, oversight of the work, partnerships and the day-to-day program administration. Based on the program results, it is clear that the funding achieved the hoped-for outcomes and has the capacity to draw universities into the orbit of hydropower and continue the conversation about industry research and development needs. The Foundation has fostered unique partnerships at the host universities and has continued to thrive with the support of the universities, advisors, industry and the DOE. The Foundation has demonstrated industry support through mentorships, partnerships, underwriting the costs and articulating the universities’ support through in-kind cost sharing. The Foundation recommends that future work be continued to nurture these graduate level programs using the initial work and improvements in the successor program, the Research Awards Program, while stimulating engagement of academia at the

  8. NRF2 Pathway Activation and Adjuvant Chemotherapy Benefit in Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Cescon, David W; She, Desmond; Sakashita, Shingo; Zhu, Chang-Qi; Pintilie, Melania; Shepherd, Frances A; Tsao, Ming-Sound

    2015-06-01

    Genomic profiling of lung squamous cell carcinomas (SCC) has identified NRF2 pathway alterations, which activate oxidative response pathways, in one third of tumors. Preclinical data suggest these tumors may be resistant to platinum-based chemotherapy. We evaluated the clinical relevance of these findings and assessed whether NRF2 activation predicts benefit from adjuvant chemotherapy in SCC. Logistic regression (LR) and significance analysis of microarrays (SAM) were applied to all 104 TCGA (The Cancer Genome Atlas) SCC cases that had microarray gene expression and mutation data to identify genes associated with somatic NRF2 pathway alterations. The resulting signature (NRF2(ACT)) was tested in 3 independent SCC datasets to evaluate its prognostic and predictive effects. IHC and sequencing for NRF2 and KEAP1 were evaluated in one cohort (n = 43) to assess the relationship between gene expression, mutational status, and protein expression. Twenty-eight genes were identified by overlap between LR (291 genes) and SAM (30 genes), and these consistently separated SCC into 2 groups in all datasets, corresponding to putatively NRF pathway-activated and wild-type (WT) tumors. NRF2(ACT) was not prognostic. However, improved survival with adjuvant chemotherapy in the JBR.10-randomized trial appears limited to patients with the WT signature (HR 0.32, P = 0.16; NRF2(ACT) HR 2.28, P = 0.48; interaction P = 0.15). NRF2(ACT) was highly correlated with mutations in NRF2 and KEAP1, and with high NRF2 protein expression. A gene expression signature of NRF2 pathway activation is associated with benefit from adjuvant cisplatin/vinorelbine in SCC. Patients with NRF2 pathway-activating somatic alterations may have reduced benefit from this therapy. ©2015 American Association for Cancer Research.

  9. Engaging Girls in STEM: A Discussion of Foundational and Current Research on What Works

    Science.gov (United States)

    Sharma, M.; Peterson, K. A.; Bleacher, L. V.; Smith, D. A.

    2012-08-01

    This article summarizes a panel discussion with Jolene Jesse (Program Director, NSF Research on Gender in Science and Engineering program) and Laura Migus (Director of Equity & Diversity at the Association of Science Technology Centers) on research related to gender in science, technology, engineering and math (STEM). Moderated by Ms. Karen Peterson from the NSF-funded National Girls Collaborative Project, Dr. Jesse and Ms. Migus discussed foundational and current research on pressing questions about the lack of gender diversity in STEM advanced education and careers, and on strategies the EPO community could employ in designing and implementing programs to encourage more girls and women to engage in STEM for the long term.

  10. 75 FR 62838 - Award of a Single-Source Expansion Supplement to the Research Foundation of CUNY on Behalf of...

    Science.gov (United States)

    2010-10-13

    ...-Source Expansion Supplement to the Research Foundation of CUNY on Behalf of Hunter College School of... single-source program expansion supplement to the Research Foundation of CUNY on behalf of Hunter College... removal, of the relative's options to become a placement resource for the child. The supplemental funding...

  11. Topical Bixin Confers NRF2-Dependent Protection Against Photodamage and Hair Graying in Mouse Skin

    Directory of Open Access Journals (Sweden)

    Montserrat Rojo de la Vega

    2018-03-01

    Full Text Available Environmental exposure to solar ultraviolet (UV radiation causes acute photodamage, premature aging, and skin cancer, attributable to UV-induced genotoxic, oxidative, and inflammatory stress. The transcription factor NRF2 [nuclear factor erythroid 2 (E2-related factor 2] is the master regulator of the cellular antioxidant response protecting skin against various environmental stressors including UV radiation and electrophilic pollutants. NRF2 in epidermal keratinocytes can be activated using natural chemopreventive compounds such as the apocarotenoid bixin, an FDA-approved food additive and cosmetic ingredient from the seeds of the achiote tree (Bixa orellana. Here, we tested the feasibility of topical use of bixin for NRF2-dependent skin photoprotection in two genetically modified mouse models [SKH1 and C57BL/6J (Nrf2+/+ versus Nrf2-/-]. First, we observed that a bixin formulation optimized for topical NRF2 activation suppresses acute UV-induced photodamage in Nrf2+/+ but not Nrf2-/- SKH1 mice, a photoprotective effect indicated by reduced epidermal hyperproliferation and oxidative DNA damage. Secondly, it was demonstrated that topical bixin suppresses PUVA (psoralen + UVA-induced hair graying in Nrf2+/+ but not Nrf2-/- C57BL/6J mice. Collectively, this research provides the first in vivo evidence that topical application of bixin can protect against UV-induced photodamage and PUVA-induced loss of hair pigmentation through NRF2 activation. Topical NRF2 activation using bixin may represent a novel strategy for human skin photoprotection, potentially complementing conventional sunscreen-based approaches.

  12. Research on the Properties of the Waste Glass Concrete Composite Foundation

    Science.gov (United States)

    Jia, Shilong; Chen, Kaihui; Chen, Zhongliang

    2018-02-01

    The composite foundation of glass concrete can not only reuse the large number of waste glass, but also improve the bearing capacity of weak foundation and soil with special properties. In this paper, the engineering properties of glass concrete composite foundation are studied based on the development situation of glass concrete and the technology of composite foundation.

  13. Annual report of Radiation Effects Research Foundation, April 1, 1992 - March 31, 1993

    International Nuclear Information System (INIS)

    1994-01-01

    This is an annual report concerning research activities and achievement in the Radiation Effects Research Foundation (RERF) in Japan during the period April 1, 1992-March 31, 1993. Twenty-nine reports, including integrated report on the incidence of solid tumors (surveyed during the period 1958-1987) and the report on the incidence of leukemia (surveyed during the period 1950-1987), were approved in the fiscal year 1992. The present report deals with scientific achievement of each division of RERF; various activities including international cooperation programs, disease monitoring workshop, lectures, and in-house seminars; abstracts of new research topics, achievement reports, and review reports; a list of publications and presentations by staff members in academic meetings; and RERF organization affairs including activities, financial aspects, and a list of visitors to RERF. An Appendix gives the proceedings; a brief summary of disease monitoring workshop; ongoing and completed research topics; and a list of RERF personnel. (N.K.)

  14. An output evaluation of a health research foundation's enhanced grant review process for new investigators.

    Science.gov (United States)

    Hammond, Gregory W; Lê, Mê-Linh; Novotny, Tannis; Caligiuri, Stephanie P B; Pierce, Grant N; Wade, John

    2017-06-19

    We assessed the ability of the Manitoba Medical Service Foundation (MMSF, a small not-for-profit foundation affiliated with Manitoba Blue Cross) to determine the best candidates for selection to receive research funding support among new researchers applying to the Research Operating Grants Programme (ROGP). Using bibliometric and grants funding analyses, we retrospectively compared indices of academic outputs from five cohorts of MMSF-funded and not MMSF-funded applicants to the annual MMSF ROGP over 2008 to 2012, from 1 to 5 years after having received evaluation decisions from the MMSF enhanced grant review process. Those researchers funded by the MMSF competition (MMSF-funded) had a statistically significant greater number of publications, a higher h-index and greater national Tri-Council (TC) funding, versus those not selected for funding (not MMSF-funded). MMSF-funded applicants and the Manitoba research community have created a strong and rapid (within 1 to 5 years of receiving the MMSF grant) local economic return on investment associated with the MMSF ROGP that supports new investigators, of approximately nine-fold for TC grants by the principal investigator, and of 34-fold for the principal investigator on collaborative (total) TC grants. The use of small amounts of seed money for competitive research grants at early stages of an MMSF-funded applicant's career correlates with future short-term success of that applicant. The ability to correctly select promising candidates who subsequently demonstrate greater academic performance after the MMSF funding shows the selection process and the ROGP to be of merit. Multiple components may have contributed to this outcome, including a direct presentation and interview process of the candidate with five-person selection subcommittees, plus an assessment by an external reviewer (the enhanced grant review process). The selection methods used here may add value to the research grant selection processes of new

  15. Corporate Foundations

    DEFF Research Database (Denmark)

    Herlin, Heidi; Thusgaard Pedersen, Janni

    2013-01-01

    action between business and NGOs through convening, translation, collaboration, and mediation. Our study provides valuable insights into the tri-part relationship of company foundation NGO by discussing the implications of corporate foundations taking an active role in the realm of corporate social...... responsibility (CSR). The paper hence illuminates the fascinating and overlooked role of corporate foundations as potential bridges between business and civil society. It also informs theory on boundary organizations by clarifying challenges and limits of such institutions.......This paper aims to explore the potential of Danish corporate foundations as boundary organizations facilitating relationships between their founding companies and non-governmental organizations (NGOs). Hitherto, research has been silent about the role of corporate foundations in relation to cross...

  16. Annual report of Radiation Effects Research Foundation, April 1, 1993 - March 31, 1994

    International Nuclear Information System (INIS)

    1995-01-01

    The circumstances that the move of the Hiroshima facilities is in the state of reservation due to the budget reduction of USA government are reported. As to the investigation and research activities, international cooperation has increased remarkably. The council resolved to request United Nations that it designates the Radiation Effects Research Foundation to the organ for inquiring about the effect of radiation on health and gives aid. The change of directors is reported. The research works in fiscal 1993 in Departments of Epidemiology, Pathological Epidemiology, Statistics, Clinical Research (in Hiroshima and Nagasaki), Genetic Biochemical Laboratory and Cell Genetics Laboratory of Genetics Department, Radiation Biology, Radiation Biology (in Nagasaki) are reported. The trend of the research works in fiscal 1994 in respective Departments is described. As to the plan of Research Information Center in fiscal 1994, the abolishment of large computer, the extension of PC network, data base management and the computer processing of office works are described. As to the plan of Research Information Center in fiscal 1995, the completion of the network connection of all computers, the expansion of the data base to input major source data sets, and the introduction of software so as to utilize and retrieve data easily are expected. The abstracts of new research plan papers and the manuscripts contributed to scientific journals are collected. (K.I.)

  17. The research-based learning development model as a foundation in generating research ideas

    Science.gov (United States)

    Puspitasari, Poppy; Dika, Johan Wayan; Permanasari, Avita Ayu

    2017-09-01

    Research Based Learning is learning that requires students to have exploration skills related to their field. By doing so, students are encouraged to create skills in managing the higherorder of abstraction in order to resolve any problems encountered. The study was done to make the schemes and sequences of learning needed by the students in order to help them to explore first ideas for their upcoming thesis. The scheme development resulted in five stages consisting of 1) identifying research journals; 2) track the development of research topics; 3) reviewing research journals; 4) discussing the results of the reviews; and 5) formulating the research topic. Furthermore, the application of 5 the stage receives percentage agreement of students was 85.9%. Therefore, it can be noted that the application of the scheme is definitely a help for students to find research ideas.

  18. Eclecticism as the foundation of meta-theoretical, mixed methods and interdisciplinary research in social sciences.

    Science.gov (United States)

    Kroos, Karmo

    2012-03-01

    This article examines the value of "eclecticism" as the foundation of meta-theoretical, mixed methods and interdisciplinary research in social sciences. On the basis of the analysis of the historical background of the concept, it is first suggested that eclecticism-based theoretical scholarship in social sciences could benefit from the more systematic research method that has been developed for synthesizing theoretical works under the name metatheorizing. Second, it is suggested that the mixed methods community could base its research approach on philosophical eclecticism instead of pragmatism because the basic idea of eclecticism is much more in sync with the nature of the combined research tradition. Finally, the Kuhnian frame is used to support the argument for interdisciplinary research and, hence, eclecticism in social sciences (rather than making an argument against multiple paradigms). More particularly, it is suggested that integrating the different (inter)disciplinary traditions and schools into one is not necessarily desirable at all in social sciences because of the complexity and openness of the research field. If it is nevertheless attempted, experience in economics suggests that paradigmatic unification comes at a high price.

  19. Rheumatology Research Foundation Clinician Scholar Educator Award: Fifteen Years Promoting Rheumatology Educators and Education.

    Science.gov (United States)

    Berman, Jessica R; O'Rourke, Kenneth S; Kolasinski, Sharon L; Aizer, Juliet; Wheatley, Mary J; Battistone, Michael J; Siaton, Bernadette C; Criscione-Schreiber, Lisa; Pillinger, Michael H; Lazaro, Deana M

    2016-11-01

    The Rheumatology Research Foundation's Clinician Scholar Educator (CSE) award is a 3-year career development award supporting medical education research while providing opportunities for mentorship and collaboration. Our objective was to document the individual and institutional impact of the award since its inception, as well as its promise to strengthen the subspecialty of rheumatology. All 60 CSE Award recipients were surveyed periodically. Fifty-six of those 60 awardees (90%) responded to requests for survey information that included post-award activities, promotions, and further funding. Data were also collected from yearly written progress reports for each grant. Of the total CSE recipients to date, 48 of 60 (80%) are adult rheumatologists, 11 of 60 (18%) are pediatric rheumatologists, and 1 is an adult and pediatric rheumatologist. Two-thirds of survey respondents spend up to 30% of their total time in educational activities, and one-third spend greater than 30%. Thirty-one of the 60 CSE recipients (52%) have published a total of 86 medical education papers. Twenty-six of 52 (50%) had received an academic promotion following the award. Eleven awardees earned advanced degrees. We describe the creation and evolution of a grant program from a medical subspecialty society foundation and the impact on producing education research, individual identity formation, and ongoing support for educators. This community of rheumatology scholar educators now serves as an important resource at the national level for the American College of Rheumatology and its membership. We believe that this grant may serve as a model for other medical societies that want to promote education scholarship and leadership within their specialties. © 2016, American College of Rheumatology.

  20. Biomedical Research Institute, Biomedical Research Foundation of Northwest Louisiana, Shreveport, Louisiana

    International Nuclear Information System (INIS)

    1992-01-01

    Department of Energy (DOE) has prepared an Environmental Assessment (EA), DOE/EA-0789, evaluating the environmental impacts of construction and operation of a Biomedical Research Institute (BRI) at the Louisiana State University (LSU) Medical Center, Shreveport, Louisiana. The purpose of the BRI is to accelerate the development of biomedical research in cardiovascular disease, molecular biology, and neurobiology. Based on the analyses in the EA, DOE has determined that the proposed action does not constitute a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act of 1969 (NEPA). Therefore, the preparation of an Environmental Impact Statement is not required

  1. The Barrett Foundation: Undergraduate Research Program for Environmental Engineers and Scientists

    Science.gov (United States)

    Rizzo, D. M.; Paul, M.; Farmer, C.; Larson, P.; Matt, J.; Sentoff, K.; Vazquez-Spickers, I.; Pearce, A. R.

    2007-12-01

    A new program sponsored by The Barrett Foundation in the University of Vermont College of Engineering and Mathematical Sciences (UVM) supports undergraduate students in Environmental Engineering, Earth and Environmental Sciences to pursue independent summer research projects. The Barrett Foundation, a non-profit organization started by a UVM Engineering alum, provided a grant to support undergraduate research. Students must work with at least two different faculty advisors to develop project ideas, then independently prepare a research proposal and submit it to a faculty panel for review. The program was structured as a scholarship to foster a competitive application process. In the last three years, fourteen students have participated in the program. The 2007 Barrett Scholars projects include: - Using bacteria to change the chemistry of subsurface media to encourage calcite precipitation for soil stability and pollutant sequestration - Assessing structural weaknesses in a historic post and beam barn using accelerometers and wireless data collection equipment - Using image processing filters to 1) evaluate leaf wetness, a leading indicator of disease in crops and 2) assess the movement of contaminants through building materials. - Investigating the impact of increased water temperature on cold-water fish species in two Vermont streams. - Studying the impacts of light duty vehicle tailpipe emissions on air quality This program supports applied and interdisciplinary environmental research and introduces students to real- world engineering problems. In addition, faculty from different research focuses are presented the opportunity to establish new collaborations around campus through the interdisciplinary projects. To date, there is a successful publication record from the projects involving the Barrett scholars, including students as authors. One of the objectives of this program was to provide prestigious, competitive awards to outstanding undergraduate engineers

  2. Support of Activities of the NAS in Relation to the Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    Douple, Evan B.

    2006-01-01

    The National Academies (NA) provides support for the activities related to the long-term follow up of the health of the survivors of the atomic bombings of Hiroshima and Nagasaki being conducted by the Radiation Effects Research Foundation (RERF) laboratories in Hiroshima and Nagasaki, Japan. The NA serves as scientific and administrative liaison between the U.S. Department of Energy (DOE) and RERF, and performs tasks in the areas of scientific oversight, information/public interface, fiscal oversight, and personnel management. The project includes recruitment and support of approximately 10 NA employees who work at RERF in Japan. Specific activities are performed consistent with the cooperative agreement's Statement of Work between DOE and NA and consistent with an Annual Work Plan developed by DOE and NA

  3. Environmental Science and Research Foundation annual technical report to DOE-ID, January , 1995--December 31, 1995

    International Nuclear Information System (INIS)

    1996-06-01

    The foundation conducts an environmental monitoring and surveillance program over an area covering much of the upper Snake River Plain and provide environmental education and support services related to INEL natural resource issues. Also, the foundation, with its university affiliates, conducts ecological and radioecological research on the Idaho National Environmental Research Park. This research benefits major DOE-ID programs including waste management, environmental restoration, spent nuclear fuels, and land management issues. Major accomplishments during CY1995 can be divided into five categories: environmental surveillance program, environmental education, environmental services and support, ecological risk assessment, and research benefitting the DOE-ID mission

  4. Environmental Science and Research Foundation annual technical report to DOE-ID, January , 1995--December 31, 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-06-01

    The foundation conducts an environmental monitoring and surveillance program over an area covering much of the upper Snake River Plain and provide environmental education and support services related to INEL natural resource issues. Also, the foundation, with its university affiliates, conducts ecological and radioecological research on the Idaho National Environmental Research Park. This research benefits major DOE-ID programs including waste management, environmental restoration, spent nuclear fuels, and land management issues. Major accomplishments during CY1995 can be divided into five categories: environmental surveillance program, environmental education, environmental services and support, ecological risk assessment, and research benefitting the DOE-ID mission.

  5. Funding of Parkinson research from industry and US federal and foundation sources.

    Science.gov (United States)

    Dorsey, E Ray; Thompson, Joel P; Frasier, Mark; Sherer, Todd; Fiske, Brian; Nicholson, Sean; Johnston, S Claiborne; Holloway, Robert G; Moses, Hamilton

    2009-04-15

    Funding for biomedical and neuroscience research has increased over the last decade but without a concomitant increase in new therapies. This study's objectives were to determine the level and principal sources of recent funding for Parkinson disease (PD) research and to determine the current state of PD drug development. We determined the level and principal sources of recent funding for PD research from the following sources: US federal agencies, large PD foundations based in the United States, and global industry. We assessed the status of PD drug development through the use of a proprietary drug pipeline database. Funding for PD research from the sources examined was approximately $1.1 billion in 2003 and $1.2 billion in 2005. Industry accounted for 77% of support from 2003 to 2005. The number of drugs in development for PD increased from 67 in 2003 to 97 in 2007. Of the companies with at least one compound in development for PD in 2007, most were small (62% had annual revenue of less than $100 million), and most (53%) were based outside the United States. These companies will likely require partnerships to drive successful development of new PD therapies.

  6. Annual report of Radiation Effects Research Foundation, April 1, 1991 - March 31, 1992

    International Nuclear Information System (INIS)

    1993-01-01

    This is an annual report concerning research activities and achievement in the Radiation Effects Research Foundation (RERF) in Japan during the period April 1, 1991-March 31, 1992. During this period, 25 publications were approved, including some epoch studies (such as the life span study that revealed a significant increase of cardiovascular disease of A-bomb survivors and the study on thyroid cancer). The present report deals with scientific achievement of each division of RERF; various activities including international cooperation programs, workshop, lectures, and in-house seminars; abstracts of new research topics, achievement reports, and review reports; a list of publications and presentations by staff members in academic meetings; and RERF organization affairs including activities, financial aspects, a list of visitors to RERF. An Appendix gives the proceedings; a brief summary of the workshop on 'the application of molecular genetics to the study of mutation in the children of A-bomb survivors' held in November 12-14, 1991; both ongoing and completed research topics as of March 31, 1992; and a list of RERF personnel. (N.K.)

  7. [Relationship between disease burden and research funding through the Health Research Foundation in Spain].

    Science.gov (United States)

    Gómez-García, Teresa; Moreno-Casbas, Teresa; González-María, Esther; Fuentelsaz-Gallego, Carmen

    2014-01-01

    To analyze the relationship between burden of disease during 2007-2009 and public funding of research in health in Spain during 2008-2010. Descriptive cross-sectional study of burden of disease and funding allocated for research in diseases in the Spanish National Health System. A review was made of a total of 6,573 project titles funded for the years 2008, 2009 and 2010. During this period, a total of 472.7 million Euros were assigned as grants for research projects. Malignant tumors and neuropsychiatric diseases were the illnesses with greatest funding support. During the study period, it was estimated that there was a total of 15,253,331.3 disability-adjusted life years (DALYs) in Spain, with neuropsychiatric diseases being the category representing most DALYs with 4,396,900 (28.8%). The relationship between funding and DALYs was obtained with a Pearson r equal to 0.759 (p<0.001). The study of congenital diseases had higher funding per DALY than any other disease with an investment of 290.4€/DALY. Among these, the study of cleft palate and esophageal atresia, with ratios of 3,432.7€/DALY and 3,387.6€/DALY respectively, obtained the greatest funding. The study shows that the relative distribution of economic resources in the study period is consistent with the burden suffered by the Spanish population. This relationship is altered by the funding of the study of congenital anomalies, because of the low number of projects in this area. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  8. Overview of Nrf2 as Therapeutic Target in Epilepsy

    Directory of Open Access Journals (Sweden)

    Liliana Carmona-Aparicio

    2015-08-01

    Full Text Available Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2, which plays a central role in the regulation of antioxidant response elements (ARE and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.

  9. Research on horizontal displacement monitoring method of deep foundation pit based on laser projecting sensing technology

    Science.gov (United States)

    Liu, Peng; Xie, Shulin; Zhang, Lixiao; Zhou, Guangyi; Zhao, Xuefeng

    2018-03-01

    A certain level of horizontal displacement will occur during excavation or subsequent construction of deep foundation pit. If the support is improper and the horizontal displacement of the foundation pit is too large, it will cause collapse and even affect the buildings around the foundation pit, which will endanger people's life and property. Therefore, the horizontal displacement monitoring of deep foundation pit becomes more and more important. At present, the electronic total station is often used to monitor the horizontal displacement of the foundation pit, but this monitoring method is expensive, prone to accidental errors, and can not be used for real-time monitoring. Therefore, a method of monitoring the horizontal displacement of deep foundation pit by using laser projection sensing technique is proposed in this paper. The horizontal displacement of the foundation pit is replaced by the displacement of the laser spot emitted by the laser, and the horizontal displacement of the foundation pit can be obtained by identifying the displacement of the laser spot projected on the screen. A series of experiments show that the accuracy of this monitoring method meets the engineering requirements and greatly reduces the cost, which provides a new technology for the displacement monitoring of deep foundation pit.

  10. [Review and analysis of transplant biological research projects funded by National Natural Science Foundation of China].

    Science.gov (United States)

    Gong, Weihua; Sun, Ruijuan; Dong, Erdan

    2015-08-01

    To study the funding and achievements in the field of organ transplantation support by the National Natural Science Foundation of China (NSFC). A search of NSFC database was made by using the key word "transplantation" and excluding "bone marrow transplantation" for the projects funded between 1988 and 2013. SCI indexed publications that marked with NSFC project number were collected by searching each grant number in the database of the Web of Science. Six hundreds fifty-five projects were identified and received about 220 million yuan in grant funding. These funded research projects were distributed among 25 provinces and autonomous regions, however, which were mainly in the developed coastal areas; of them, 43 (6.56%) projects were granted in xenotransplantation and 17 projects (2.60%) were funded in the field of traditional Chinese medicine-related organ transplantation; Transplantation on blood vessels, heart, kidney, liver, lung, small intestine, pancreatic, cornea, trachea, skin, etc. were primarily performed in research. Nine hundreds and sixty-one SCI-indexed publications were achieved. Magnitude and intensity of NSFC funding, output of SCI publications have been increasing, suggesting that NSFC positively promotes the development of organ transplantation. Although a great progress of transplantation has been made, basic and translational studies should be vigorously strengthened.

  11. Engaging Girls in STEM: A Discussion of Foundational and Current Research on What Works

    Science.gov (United States)

    Peterson, K.; Jesse, J.; Migus, L. H.

    2012-08-01

    Diversity in science, technology, engineering, and mathematics (STEM) education and careers occupies center stage in national discussions on U.S. competitiveness in the 21st century. Women constitute roughly half the total workforce in the U.S., but they hold just 25% of mathematical and science jobs and 11% of engineering jobs. Women earn nearly 60% of all bachelors and masters degrees, except in physics, computer science, and engineering, where the percentages are 20-25%. This disparity is even more pronounced at the doctoral level, where women earn fewer than 20% of awarded Ph.D.'s in physics or engineering. However, at the high school level, there is far less gender disparity: both female and male students take comparable advanced physical science and math courses. What, then, accounts for the lack of gender diversity in STEM advanced education and career paths? In fact, there is no consensus even among experts. So, what information and strategies do the EPO community need to know and include as part of designing and implementing programs to encourage more girls and women to engage in STEM for the long term? The panelists will discuss foundational and current research on pressing questions on why these trends exist and what can be done to change them. They will highlight research and evaluation results from programs that are successfully engaging girls in STEM.

  12. Cancer risk among atomic bomb survivors. The RERF Life Span Study. Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    Shimizu, Y.; Schull, W.J.; Kato, H.

    1990-01-01

    This article summarizes the risk of cancer among the survivors of the atomic bombing of Hiroshima and Nagasaki. We focus primarily on the risk of death from cancer among individuals in the Life Span Study sample of the Radiation Effects Research Foundation from 1950 through 1985 based on recently revised dosimetry procedures. We report the risk of cancer other than leukemia among the atomic bomb survivors. We note that the number of excess deaths of radiation-induced malignant tumors other than leukemia increases with age. Survivors who were exposed in the first or second decade of life have just entered the cancer-prone age and have so far exhibited a high relative risk in association with radiation dose. Whether the elevated risk will continue or will fall with time is not yet clear, although some evidence suggests that the risk may be declining. It is important to continue long-term follow-up of this cohort to document the changes with time since exposure and to provide direct rather than projected risks over the lifetime of an exposed individual

  13. Activities of the National Academy of Sciences in relation to the Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    Edington, C.W.

    1991-02-01

    The activities of the National Academy of Sciences (NAS), in relation to the Radiation Effects Research Foundation (RERF), has a long history and the specific time period supported by this contract is but a small piece of the long-term continuing program. As a background, in August 1945, atomic bombs were dropped on Hiroshima (6 August) and Nagasaki (9 August). Shortly after the bombings, US medical teams joined forces with their Japanese counterparts to form a Joint Commission for the Investigation of the Effects of the Atomic Bombs. As a result of the Joint Commission's investigations, it was determined that consideration should be given to the establishment of a long-term study of the potential late health effects of exposure of the survivors to radiation from the bombs. The results obtained from RERF studies contribute the vast majority of information that provides a better understanding of radiation effects on humans. This information has been used extensively by national organizations and international committees for estimating risks associated with radiation exposures. The estimated risks developed by these independent organizations are used by government agencies around the world to establish standards for protection of individuals exposed in the occupational, medical, and general environment. Some of these results are described briefly in this report

  14. Nrf2 protects against airway disorders

    International Nuclear Information System (INIS)

    Cho, Hye-Youn; Kleeberger, Steven R.

    2010-01-01

    Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.

  15. A positive return on investment: research funding by the Thoracic Surgery Foundation for Research and Education (TSFRE).

    Science.gov (United States)

    Jones, David R; Mack, Michael J; Patterson, G Alexander; Cohn, Lawrence H

    2011-05-01

    The Thoracic Surgery Foundation for Research and Education (TSFRE) was formed in 1991 with the primary goals of generating new knowledge and nurturing the development of surgeon-scientists. The purpose of this article is to determine how effective the TSFRE has been in achieving these goals. A survey instrument was sent electronically to all former and current TSFRE research award recipients. Major themes included the benefits on TSFRE award recipients with respect to career choices of thoracic surgery, progress toward research independence, and the ability to leverage TSFRE funds to more substantive National Institutes of Health (NIH) awards. Success rates for NIH funding were confirmed using NIH Research Portfolio Online Reporting Tools. The total completed survey response rate was 70% (75/107). The response rates for each group were as follows: resident 74% (28/38), faculty 85% (29/34), Braunwald 50% (9/18), and TSFRE/NIH K-award 65% (11/17). The funding rate for all grants was 14% (90/619). For resident research awardees, 81% (34/42) are cardiothoracic surgeons or are thoracic surgery residents. The conversion rate for existing TSFRE/NIH co-sponsored K-awards to R01 grants is 40% at 5 years compared with a 20% K to R conversion rate for all NIH K-award recipients. K to R conversion rates for junior faculty grant awardees without a prior K-award is 44%, which is much higher than NIH rates for all new investigator R01 awards. The return on investment for TSFRE funding for surgeon-scientists is resoundingly positive with respect to promoting careers in cardiothoracic surgery and to obtaining subsequent NIH funding for thoracic surgeon investigators. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  16. Research Misconduct in National Science Foundation Funded Research: A Mixed-Methods Analysis of 2007-2011 Research Awards

    Science.gov (United States)

    Masters, Elizabeth A.

    2013-01-01

    Research is an important aspect of academic institutions as it brings funding, reputation, and other benefits to the associated establishment. Research misconduct in the form of plagiarism, fabrication, and falsification can occur in association with research, along with subsequent penalties. The problem of the poorly established prevalence of the…

  17. Starting Where the People Are: The African Medical and Research Foundation (AMREF). Carnegie Quarterly, Volume XXXII, Number 2.

    Science.gov (United States)

    Carnegie Quarterly, 1987

    1987-01-01

    This issue of the "Carnegie Quarterly" describes three projects that are being conducted by the African Medical and Research Foundation (AMREF). The projects are the following: (1) building community participation in health care at Lake Kenyatta; (2) the role of community education in disease control among the Turkana people at…

  18. Nrf2 the rescue: Effects of the antioxidative/electrophilic response on the liver

    International Nuclear Information System (INIS)

    Klaassen, Curtis D.; Reisman, Scott A.

    2010-01-01

    Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes. These gene products include proteins that catalyze reduction reactions (NAD(P)H:quinone oxidoreductase 1, Nqo1), conjugation reactions (glutathione-S-transferases, Gsts and UDP-glucuronosyltransferases, Ugts), as well as the efflux of potentially toxic xenobiotics and xenobiotic conjugates (multidrug resistance-associated proteins, Mrps). The significance of Nrf2 in the liver has been established, as livers of Nrf2-null mice are more susceptible to various oxidative/electrophilic stress-induced pathologies than wild-type mice. In contrast, both pharmacological and genetic models of hepatic Nrf2 activation are protective against oxidative/electrophilic stress. Furthermore, because certain Nrf2-target genes in the liver could affect the distribution, metabolism, and excretion of xenobiotics, the effects of Nrf2 on the kinetics of drugs and other xenobiotics should also be considered, with a special emphasis on metabolism and excretion. Therefore, this review highlights the research that has contributed to the understanding of the importance of Nrf2 in toxicodynamics and toxicokinetics, especially that which pertains to the liver.

  19. Expression of Nrf2 in neurodegenerative diseases.

    Science.gov (United States)

    Ramsey, Chenere P; Glass, Charles A; Montgomery, Marshall B; Lindl, Kathryn A; Ritson, Gillian P; Chia, Luis A; Hamilton, Ronald L; Chu, Charleen T; Jordan-Sciutto, Kelly L

    2007-01-01

    In response to oxidative stress, the nuclear factor E2-related factor 2 (Nrf2) transcription factor translocates from the cytoplasm into the nucleus and transactivates expression of genes with antioxidant activity. Despite this cellular mechanism, oxidative damage is abundant in Alzheimer and Parkinson disease (AD and PD). To investigate mechanisms by which Nrf2 activity may be aberrant or insufficient in neurodegenerative conditions, we assessed Nrf2 localization in affected brain regions of AD, Lewy body variant of AD (LBVAD), and PD. By immunohistochemistry, Nrf2 is expressed in both the nucleus and the cytoplasm of neurons in normal hippocampi with predominant expression in the nucleus. In AD and LBVAD, Nrf2 was predominantly cytoplasmic in hippocampal neurons and was not a major component of beta amyloid plaques or neurofibrillary tangles. By immunoblotting, we observed a significant decrease in nuclear Nrf2 levels in AD cases. In contrast, Nrf2 was strongly nuclear in PD nigral neurons but cytoplasmic in substantia nigra of normal, AD, and LBVAD cases. These findings suggest that Nrf2-mediated transcription is not induced in neurons in AD despite the presence of oxidative stress. In PD, nuclear localization of Nrf2 is strongly induced, but this response may be insufficient to protect neurons from degeneration.

  20. Nrf2 Activation Protects against Solar-Simulated Ultraviolet Radiation in Mice and Humans.

    Science.gov (United States)

    Knatko, Elena V; Ibbotson, Sally H; Zhang, Ying; Higgins, Maureen; Fahey, Jed W; Talalay, Paul; Dawe, Robert S; Ferguson, James; Huang, Jeffrey T-J; Clarke, Rosemary; Zheng, Suqing; Saito, Akira; Kalra, Sukirti; Benedict, Andrea L; Honda, Tadashi; Proby, Charlotte M; Dinkova-Kostova, Albena T

    2015-06-01

    The transcription factor Nrf2 determines the ability to adapt and survive under conditions of electrophilic, oxidative, and inflammatory stress by regulating the expression of elaborate networks comprising nearly 500 genes encoding proteins with versatile cytoprotective functions. In mice, disruption of Nrf2 increases susceptibility to carcinogens and accelerates disease pathogenesis. Paradoxically, Nrf2 is upregulated in established human tumors, but whether this upregulation drives carcinogenesis is not known. Here we show that the incidence, multiplicity, and burden of solar-simulated UV radiation-mediated cutaneous tumors that form in SKH-1 hairless mice in which Nrf2 is genetically constitutively activated are lower than those that arise in their wild-type counterparts. Pharmacologic Nrf2 activation by topical biweekly applications of small (40 nmol) quantities of the potent bis(cyano enone) inducer TBE-31 has a similar protective effect against solar-simulated UV radiation in animals receiving long-term treatment with the immunosuppressive agent azathioprine. Genetic or pharmacologic Nrf2 activation lowers the expression of the pro-inflammatory factors IL6 and IL1β, and COX2 after acute exposure of mice to UV radiation. In healthy human subjects, topical applications of extracts delivering the Nrf2 activator sulforaphane reduced the degree of solar-simulated UV radiation-induced skin erythema, a quantifiable surrogate endpoint for cutaneous damage and skin cancer risk. Collectively, these data show that Nrf2 is not a driver for tumorigenesis even upon exposure to a very potent and complete carcinogen and strongly suggest that the frequent activation of Nrf2 in established human tumors is a marker of metabolic adaptation. ©2015 American Association for Cancer Research.

  1. The Development of the Foundations of Modern Pedagogy: Paradigmal and Methodological Aspects of Research

    Science.gov (United States)

    Dmitrenko, ?amara ?.; Lavryk, Tatjana V.; Yaresko, Ekaterina V.

    2015-01-01

    Changes in the various fields of knowledge influenced the pedagogical science. The article explains the structure of the foundations of modern pedagogy through paradigmal and methodological aspects. Bases of modern pedagogy include complex of paradigms, object and subject of science, general and specific principles, methods and technologies.…

  2. Effective Dropout Prevention Strategies Developed by the High/Scope Educational Research Foundation.

    Science.gov (United States)

    Stellar, Arthur

    2002-01-01

    Introduces a collection of papers that address the High/Scope Foundation's approach to risk reduction and dropout prevention. Examines High/Scope's history and describes various High/Scope efforts (e.g., the Michigan School Readiness Program Evaluation, preschool and elementary curriculum development and training, movement and music curriculum…

  3. Taking stock of the ethical foundations of international health research: pragmatic lessons from the IU-Moi Academic Research Ethics Partnership.

    Science.gov (United States)

    Meslin, Eric M; Were, Edwin; Ayuku, David

    2013-09-01

    It is a sine qua non that research and health care provided in international settings raise profound ethical questions when different cultural and political values are implicated. Yet ironically, as international health research expands and as research on ethical issues in international health research broadens and deepens, we appear to have moved away from discussing the moral foundations of these activities. For international health research to thrive and lead to the kind of benefits it is capable of, it is helpful to occasionally revisit the foundational premises that justify the enterprise as a whole. We draw on the experience of the Indiana University-Moi University Academic Research Ethics Partnership, an innovative bioethics training program co-located in Indianapolis and Eldoret, Kenya to highlight the changing nature of ethical issues in international health research and the ongoing practical challenges.

  4. Application and research of recyclable cables in foundation pit support engineering

    Science.gov (United States)

    Zheng, Suping

    2018-05-01

    Anchoring cables are widely used in the construction of foundation pit as a temporary support structure. After the construction is completed, the anchor cables left in the ground will not only cause environmental pollution but also cause a great waste of resources. The emergence of recyclable cable technology, to avoid such problems, to achieve the secondary use of the anchor cable, excavation in the excavation project is more and more widely used. Combined with the design and construction of recoverable anchor cable in engineering practice, the application effect of recoverable anchor cable in foundation pit support is analyzed, and the conclusion that the support effect of recoverable anchor cable is stable and safe can be obtained Recyclable anchor cable in the future support projects to provide a reference.

  5. Targeting the Nrf2/Amyloid-Beta Liaison in Alzheimer's Disease: A Rational Approach.

    Science.gov (United States)

    Simoni, Elena; Serafini, Melania M; Caporaso, Roberta; Marchetti, Chiara; Racchi, Marco; Minarini, Anna; Bartolini, Manuela; Lanni, Cristina; Rosini, Michela

    2017-07-19

    Amyloid is a prominent feature of Alzheimer's disease (AD). Yet, a linear linkage between amyloid-β peptide (Aβ) and the disease onset and progression has recently been questioned. In this context, the crucial partnership between Aβ and Nrf2 pathways is acquiring paramount importance, offering prospects for deciphering the Aβ-centered disease network. Here, we report on a new class of antiaggregating agents rationally designed to simultaneously activate transcription-based antioxidant responses, whose lead 1 showed interesting properties in a preliminary investigation. Relying on the requirements of Aβ recognition, we identified the catechol derivative 12. In SH-SY5Y neuroblastoma cells, 12 combined remarkable free radical scavenger properties to the ability to trigger the Nrf2 pathway and induce the Nrf2-dependent defensive gene NQO1 by means of electrophilic activation of the transcriptional response. Moreover, 12 prevented the formation of cytotoxic stable oligomeric intermediates, being significantly more effective, and per se less toxic, than prototype 1. More importantly, as different chemical features were exploited to regulate Nrf2 and Aβ activities, the two pathways could be tuned independently. These findings point to compound 12 and its derivatives as promising tools for investigating the therapeutic potential of the Nrf2/Aβ cellular network, laying foundation for generating new drug leads to confront AD.

  6. The Research on Subsidence Prediction of Soils Around Deep Foundation Pit

    Directory of Open Access Journals (Sweden)

    Ge LIU

    2014-12-01

    Full Text Available Deep foundation pit will cause settlement of surround buildings in the process of excavation. When the settlement is excessive, it will give rise to safety issues. Subsidence monitoring has become an important measure to ensure the safety of deep foundation pits. But in current subsidence monitoring engineering, the costs of wiring, unwiring and installation are particularly high. This paper proposes a portable wireless data transmission device in forecasting and early warning of settlement deformation of soils around deep foundation pits. We solve the problem by adopting the means of wireless communication to replace the cable transmission link part. The device does not rely on any personal computers. Instead, it can directly deal with the collected data through grey prediction GM (1, 1 mathematical model, neural network and interpolation model to give short-term, medium- term and long-term forecasts, respectively. Additionally it is able to set a threshold value. Once the forecast data reach the threshold, the device can issue alert and achieve the target of reminding technicians, so as to provide reliable basis to prevent and reduce disasters.

  7. RESEARCH OF THE FOUNDATION CONSOLIDATED BY DIFFERENT-SIZED HORIZONTAL ELEMENTS

    Directory of Open Access Journals (Sweden)

    Isakova Elena Aleksandrovna

    2016-05-01

    Full Text Available The article is dedicated to the problem of geotechnics. The problems of the weak soil base are topical. Also there sometimes happen severe accidents of soil mass. A great number of such emergencies is of a progressive character, when a local crash leads to the crash of the whole construction. Tarring the soil with epoxy can ensure geotechnical safety of the basis. That’s why the improvement of this method is needed in order to reduce yielding of the base, create ground water cutoff or create building hoisting. In the article new structural solutions for reduction of settlement are presented. The authors suggest using the manufactured plane elements containing epoxy. Such elements have different sizes and lie underneath the foundation. Similar structural scheme can be used to reduce soil settlement. The authors carried out two series of plate-bearing model tests with manufactured plane epoxy elements. In the first series of tests the biggest element was closer to the foundation, the smallest element was closer to the biggest element. In the second series of tests the smallest element was closer to the foundation, the biggest element was closer to the smallest element. After the end of plate-bearing model tests the authors received values of the base settlement and the dependency diagrams “base settlement-soil pressure”. The new structural solution for reducing soil settlement proved to be effective. Settlement of base decreased sevenfold.

  8. The Role of Nrf2: Adipocyte Differentiation, Obesity, and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Hyun-Ae Seo

    2013-01-01

    Full Text Available Metabolic diseases, such as type 2 diabetes and obesity, are increasing globally, and much work has been performed to elucidate the regulatory mechanisms of these diseases. Nuclear factor E2-related factor 2 (Nrf2 is a basic leucine zipper transcription factor that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. Recent studies have proposed a close relationship between oxidative stress and energy metabolism-associated disease. The Nrf2 pathway, as a master regulator of cellular defense against oxidative stress, has emerged as a critical target of energy metabolism; however, its effects are controversial. This review examines the current state of research on the role of Nrf2 on energy metabolism, specifically with respect to its participation in adipocyte differentiation, obesity, and insulin resistance, and discusses the possibility of using Nrf2 as a therapeutic target in the clinic.

  9. A Good Foundation for Number Learning for Five-Year-Olds? An Evaluation of the English Early Learning "Numbers" Goal in the Light of Research

    Science.gov (United States)

    Gifford, Sue

    2014-01-01

    This article sets out to evaluate the English Early Years Foundation Stage Goal for Numbers, in relation to research evidence. The Goal, which sets out to provide "a good foundation in mathematics", has greater breadth of content and higher levels of difficulty than previous versions. Research suggests that the additional expectations…

  10. Targeting NRF2 signaling for cancer chemoprevention

    International Nuclear Information System (INIS)

    Kwak, Mi-Kyoung; Kensler, Thomas W.

    2010-01-01

    Modulation of the metabolism and disposition of carcinogens through induction of cytoprotective enzymes is one of several promising strategies to prevent cancer. Chemopreventive efficacies of inducers such as dithiolethiones and sulforaphane have been extensively studied in animals as well as in humans. The KEAP1-NRF2 system is a key, but not unilateral, molecular target for these chemopreventive agents. The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of the expression of a subset of genes, which produce proteins responsible for the detoxication of electrophiles and reactive oxygen species as well as the removal or repair of some of their damage products. It is believed that chemopreventive enzyme inducers affect the interaction between KEAP1 and NRF2 through either mediating conformational changes of the KEAP1 protein or activating phosphorylation cascades targeting the KEAP1-NRF2 complex. These events in turn affect NRF2 stability and trafficking. Recent advances elucidating the underlying structural biology of KEAP1-NRF2 signaling and identification of the gene clusters under the transcriptional control of NRF2 are facilitating understanding of the potential pleiotropic effects of NRF2 activators and discovery of novel classes of potent chemopreventive agents such as the triterpenoids. Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, especially as the pathway affects cell survival and drug resistance, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

  11. The Danish Industrial Foundations

    DEFF Research Database (Denmark)

    Thomsen, Steen

    and governed, what role it plays in the Danish economy, and how industrial foundation-owned companies perform. The book is the result of a large collaborative research project, led by the author, on industrial foundations. Some global companies such as IKEA, Robert Bosch or the Tata Group are foundation...

  12. An essential role of Nrf2 in American ginseng-mediated anti-oxidative actions in cardiomyocytes.

    Science.gov (United States)

    Li, Jinqing; Ichikawa, Tomonaga; Jin, Yu; Hofseth, Lorne J; Nagarkatti, Prakash; Nagarkatti, Mitzi; Windust, Anthony; Cui, Taixing

    2010-07-20

    Ginseng has been used as a folk medicine for thousands of years in Asia, and has become a popular herbal medicine world-wide. Recent studies have revealed that ginseng, including American ginseng, exerts antioxidant effects in the cardiovascular system; however, the underlying mechanisms are not fully understood. Thus, we investigated role of Nrf2, a master transcription factor of endogenous anti-oxidative defense systems, in the regulation of American ginseng-mediated anti-oxidative actions in cardiomyocytes. A standardized crude extract of American ginseng was supplied by the National Research Council of Canada, Institute for National Measurement Standards. H9C2 cells, a rat cardiomyocyte cell line, were exposed to angiotensin II (Ang II) or tumor necrosis factor alpha (TNFalpha) to induce oxidative stress that was examined by measuring formation of reactive oxygen and nitrogen species. Oxidative stress-induced cell death was induced by exogenous addition of hydrogen peroxide (H(2)O(2)). Proteins were measured by Western blot and mRNA expression was determined by quantitative real time PCR. Nrf2-driven transcriptional activity was assessed by antioxidant response element (ARE)-luciferase reporter assay. Direct Nrf2 binding to its target gene promoters was determined by chromatin immunoprecipitation assay. Adenoviral over-expression of Nrf2 shRNA was utilized to knock down Nrf2 in H9C2 cells. Immunochemical staining was applied for Nrf2 expression in the heart. American ginseng induced dramatic increases in Nrf2 protein expression, Nrf2 nuclear translocation, Nrf2 transcriptional activity, direct Nrf2 binding to its target gene promoters, and expression of a group of anti-oxidative genes driven by Nrf2 in H9C2 cells. In addition, American ginseng inhibited Ang II- or TNFalpha-induced free radical formation and H(2)O(2)-induced cell death in H9C2 cells over-expressed with control shRNA but not in the cells over-expressed with Nrf2 shRNA. Finally, oral

  13. Evaluasi Karakteristik XBee Pro dan nRF24L01+ sebagai Transceiver Nirkabel

    Directory of Open Access Journals (Sweden)

    BURHAN FAJRIANSYAH

    2016-01-01

    Full Text Available ABSTRAK Pemillihan modul transciever sebagai media transmisi data digital menjadi permasalahan bagi perancang ketika mendesain suatu sistem komunikasi nirkabel. Pada penelitian ini penulis melakukan evaluasi pada dua modul transceiver yaitu XBee Pro dan nRFf24L01+ dengan tujuan untuk menentukan modul transceiver mana yang tepat digunakan untuk kebutuhan perancangan sistem Wireless Sensor Network (WSN. Evaluasi dilakukan dengan mengirimkan data dalam bentuk karakter ASCII/ bytes secara kontinyu maupun sekuensial melalui komunikasi serial UART. Pada pengaturan untuk mode data rate 250 Kbps, XBee Pro memiliki data rate 27 Kbps dan nRF24L01+ 16 Kbps untuk protokol komunikasi serial UART. Modul nRF24L01+ lebih unggul dalam mengirimkan data secara streaming (kontinyu dibandingkan Xbee Pro, dan nRF24L01+ memiliki Round Time Trip (RTT tercepat 0,003 sekon sedangkan XBee Pro hanya 0,036sekon. Pada aplikasi dalam ruangan XBee Pro memiliki performa lebih tinggi karena lebih stabil dalam transmisi dengan hambatan 4 dinding sedangkan nRF24L01+ hanya 2 dinding. Kata kunci: UART, Data Rate, Nirkabel, XBee Pro, nRF24L01+.   ABSTRACT Chosing transciever module as a media for a digital transmission data has becoming a serious problem for a designer to design a wireless communication system. In this research, author do the evaluation for a two transceiver module that are XBee Pro and nRF24L01+, the purpose is to chose which the right transceiver module that designer need to make a Wireless Sensor Network (WSN system. The evaluation was done by sending a data in ASCII character/ bytes as continuous and sequensial method using serial communication UART. When data rate is set to 250 Kbps mode, XBee Pro data rate is 27 Kbps and nRF24L01+ 16Kbps for serial communicaton UART purpose. nRF24L01+ is better at sending a streaming data (continuous than XBee Pro, and also nRF24L01+ has a fastest Round Time Trip (RTT that are 0,003 sec while XBee Pro only 0,036 sec. For

  14. An overview of the molecular mechanisms and novel roles of Nrf2 in neurodegenerative disorders.

    Science.gov (United States)

    Yang, Yang; Jiang, Shuai; Yan, Juanjuan; Li, Yue; Xin, Zhenlong; Lin, Yan; Qu, Yan

    2015-02-01

    Recently, growing evidence has demonstrated that nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal regulator of endogenous defense systems that function via the activation of a set of protective genes, and this is particularly clear in the central nervous system (CNS). Therefore, it is highly useful to summarize the current literature on the molecular mechanisms and role of Nrf2 in the CNS. In this review, we first briefly introduce the molecular features of Nrf2. We then discuss the regulation, cerebral actions, upstream modulators and downstream targets of Nrf2 pathway. Following this background, we expand our discussion to the role of Nrf2 in several major neurodegenerative disorders (NDDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis and amyotrophic lateral sclerosis. Lastly, we discuss some potential future directions. The information reviewed here may be significant in the design of further experimental research and increase the potential of Nrf2 as a therapeutic target in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Getting Its Ducks in a Row? Qatar Foundation's Agreement with HEC Paris and the Launch of the Qatar Foundation Management, Education and Research Centre

    Science.gov (United States)

    Observatory on Borderless Higher Education, 2010

    2010-01-01

    Last week, private, non-profit organisation the Qatar Foundation (QF) announced a partnership agreement with French business institution HEC Paris to offer executive education programmes. According to the terms of the agreement, a full-time faculty will provide executive and short certificate programmes and corporate-specific training, including…

  16. Cold Climate Foundation Retrofit Experimental Hygrothermal Performance. Cloquet Residential Research Facility Laboratory Results

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Louise F. [NorthernSTAR, St. Paul, MN (United States); Harmon, Anna C. [NorthernSTAR, St. Paul, MN (United States)

    2015-04-09

    This project was funded jointly by the National Renewable Energy Laboratory (NREL) and Oak Ridge National Laboratory (ORNL). ORNL focused on developing a full basement wall system experimental database to enable others to validate hygrothermal simulation codes. NREL focused on testing the moisture durability of practical basement wall interior insulation retrofit solutions for cold climates. The project has produced a physically credible and reliable long-term hygrothermal performance database for retrofit foundation wall insulation systems in zone 6 and 7 climates that are fully compliant with the performance criteria in the 2009 Minnesota Energy Code. These data currently span the period from November 10, 2012 through May 31, 2014 and are anticipated to be extended through November 2014. The experimental data were configured into a standard format that can be published online and that is compatible with standard commercially available spreadsheet and database software.

  17. The Minneapolis Heart Institute Foundation Summer Research Internship Program: the benefits of preprofessional experience for prospective physicians.

    Science.gov (United States)

    Willenbring, Benjamin D; McKee, Katherine C; Wilson, Betsy V; Henry, Timothy D

    2008-08-01

    There is a distinct shortage of preprofessional opportunities for undergraduate premedical students. During the last 7 summers, the Minneapolis Heart Institute Foundation Summer Research Internship Program has exposed interested students to cardiology and clinical research. The goals of the internship program are threefold: to bring students in contact with the medical profession, to offer experiences in the various disciplines of cardiology, and to introduce students to clinical research. The success of the program can be measured by its influence on participants' academic pursuits and scholarly contributions. Of the 65 internship alumni, 52 are studying to become physicians and most of the others are in health-related fields. Interns have also contributed abstracts and manuscripts to peer-reviewed journals and presented their research at major conferences.

  18. The New Aphrodite school on Disasters Food and Poverty organized by CIMA Research Foundation and University of Genova

    Science.gov (United States)

    Boni, G.

    2009-04-01

    CIMA is a Research Foundation which aim is to advance science and engineering in environmentally related fields, focusing on public health and safety, civil protection and the preservation of terrestrial and water-related ecosystems. This aim is accomplished through scientific research, technology transfer and high level training services. Here we present the "New Aphrodite school on Disasters Food and Poverty" jointly managed by CIMA Foundation, and the University of Genova. The school is organized to provide to international students, professionals and government officials, mainly from poor or developing countries, formation for the management, prediction and prevention of natural and man made disasters. The expertise of the teachers, mainly CIMA's researchers, comes from a long term support of CIMA Foundation to the Italian Civil Protection in developing the advanced national system for risk prediction, prevention and management. The school is organized in two levels. The first level includes an international master of science degree in "Environmental Engineering: Sustainable Development and Risk Management", which classes are given in English, and a master for professional and government officials in "Disasters, food and poverty". The second level includes an international Ph.D. programme in "Information sciences and technologies for system monitoring and environmental risk management". Short training courses for international government official are periodically organized. At present the school is organizing short courses for officials of Civil Protections of Venezuela, Barbados and Mozambique. The philosophy underlying the teaching activities is to promote a multi-disciplinary approach to disaster mitigation, prevention and prediction. Special focus is on the potential of high-tech low-cost technologies for rapid communication and disaster monitoring, such as satellite based technologies. Such technologies are seen as the best way to support the development

  19. Assessing the Success of ICT¡¯s from a User Perspective: Case Study of Coffee Research Foundation, Kenya

    OpenAIRE

    Michael W. Makokha; Daniel O. Ochieng

    2014-01-01

    The study was conducted to validate the application of DeLone & McLean¡¯s Information System (IS) success model (2003) in a local setup in Kenya and to evaluate the success of an enterprise resource planning (ERP) system from a user perspective. It was carried out at Coffee Research Foundation (CRF) in Kenya. A number of past studies to measure the success of information systems in different settings were reviewed leading to the choice and use of the updated DeLone & McLean IS success model i...

  20. Building a Foundation for Effective Technology Transfer through Integration with the Research Process : a Primer.

    Science.gov (United States)

    2016-03-01

    This primer aims to increase the effectiveness of T2 activity in transportation by describing how T2 practices can be successfully integrated into : the research process to capture the potential real-world benefits of our communitys research inves...

  1. ABIM Foundation

    Science.gov (United States)

    ... In conjunction with the… mailchi.mp View on Facebook ABIM Foundation shared Business Radio Powered by The Wharton School's post. 2 days ago View on Facebook ABIM Foundation 2 days ago The Android version ...

  2. Cold Climate Foundation Retrofit Experimental Hygrothermal Performance: Cloquet Residential Research Facility Laboratory Results

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Louise F. [NorthernSTAR, St. Paul, MN (United States); Harmon, Anna C. [NorthernSTAR, St. Paul, MN (United States)

    2015-04-01

    Thermal and moisture problems in existing basements create a unique challenge because the exterior face of the wall is not easily or inexpensively accessible. This approach addresses thermal and moisture management from the interior face of the wall without disturbing the exterior soil and landscaping. the interior and exterior environments. This approach has the potential for improving durability, comfort, and indoor air quality. This project was funded jointly by the National Renewable Energy Laboratory (NREL) and Oak Ridge National Laboratory (ORNL). ORNL focused on developing a full basement wall system experimental database to enable others to validate hygrothermal simulation codes. NREL focused on testing the moisture durability of practical basement wall interior insulation retrofit solutions for cold climates. The project has produced a physically credible and reliable long-term hygrothermal performance database for retrofit foundation wall insulation systems in zone 6 and 7 climates that are fully compliant with the performance criteria in the 2009 Minnesota Energy Code. The experimental data were configured into a standard format that can be published online and that is compatible with standard commercially available spreadsheet and database software.

  3. INTRODUCTION TO THE MOVEMENT SYSTEM AS THE FOUNDATION FOR PHYSICAL THERAPIST PRACTICE EDUCATION AND RESEARCH.

    Science.gov (United States)

    Saladin, Lisa; Voight, Michael

    2017-11-01

    In 2013, the American Physical Therapy Association (APTA) adopted an inspiring new vision, "Transforming society by optimizing movement to improve the human experience." This new vision for our profession calls us to action as physical therapists to transform society by using our skills, knowledge, and expertise related to the movement system in order to optimize movement, promote health and wellness, mitigate the progression of impairments, and prevent the development of (additional) disability. The guiding principle of the new vision is "identity," which can be summarized as "The physical therapy profession will define and promote the movement system as the foundation for optimizing movement to improve the health of society." Recognition and validation of the movement system is essential to understand the structure, function, and potential of the human body. As currently defined, the "movement system" represents the collection of systems (cardiovascular, pulmonary, endocrine, integumentary, nervous, and musculoskeletal) that interact to move the body or its component parts. By better characterizing physical therapists as movement system experts, we seek to solidify our professional identity within the medical community and society. The physical therapist will be responsible for evaluating and managing an individual's movement system across the lifespan to promote optimal development; diagnose impairments, activity limitations, and participation restrictions; and provide interventions targeted at preventing or ameliorating activity limitations and participation restrictions. 5.

  4. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    Science.gov (United States)

    ... SADS Foundation UK SADS Foundation Netherlands SADS Foundation China SADS Foundation Hong Kong Search for: Log in ... research crucial for health of patients and the economy 7/18/2017 More funding for heart disease ...

  5. An Analysison Provincial Medical Science Basic Research Competitiveness Based on the National Natural Science Foundation of China

    Directory of Open Access Journals (Sweden)

    Xing Xia

    2017-06-01

    Full Text Available [Purpose/significance] The National Natural Science Foundation of China (NSFC is one of the most important channels to support basic research in China. Competition for funding by the NSFC has been a very important indicator to measure the basic research level of various province and scientific research institutions. [Method/process] By combing and analyzing the status quo of NSFC in medical science, it is helpful to narrow the provincial gap and improve the basic research of medical science in China. Based on the project information of NSFC and previous scholars’ research, the paper update the index of basic research competitiveness, and analyzes project number and project funding of medical science during 2006-2016. At the same time, the competitiveness of medical science basic research and its changing trend in 31 provinces of China are analyzed. [Result/conclusion] The result shows that, in recent years, China’s basic scientific research has greatly improved, but there is a large gap between the provinces.

  6. Using Microbial Genome Annotation as a Foundation for Collaborative Student Research

    Science.gov (United States)

    Reed, Kelynne E.; Richardson, John M.

    2013-01-01

    We used the Integrated Microbial Genomes Annotation Collaboration Toolkit as a framework to incorporate microbial genomics research into a microbiology and biochemistry course in a way that promoted student learning of bioinformatics and research skills and emphasized teamwork and collaboration as evidenced through multiple assessment mechanisms.…

  7. Nrf2 mediates redox adaptations to exercise

    Directory of Open Access Journals (Sweden)

    Aaron J. Done

    2016-12-01

    Full Text Available The primary aim of this review is to summarize the current literature on the effects of acute exercise and regular exercise on nuclear factor erythroid 2-related factor 2 (Nrf2 activity and downstream targets of Nrf2 signaling. Nrf2 (encoded in humans by the NFE2L2 gene is the master regulator of antioxidant defenses, a transcription factor that regulates expression of more than 200 cytoprotective genes. Increasing evidence indicates that Nrf2 signaling plays a key role in how oxidative stress mediates the beneficial effects of exercise. Episodic increases in oxidative stress induced through bouts of acute exercise stimulate Nrf2 activation and when applied repeatedly, as with regular exercise, leads to upregulation of endogenous antioxidant defenses and overall greater ability to counteract the damaging effects of oxidative stress. The evidence of Nrf2 activation in response to exercise across variety of tissues may be an important mechanism of how exercise exerts its well-known systemic effects that are not limited to skeletal muscle and myocardium. Additionally there are emerging data that results from animal studies translate to humans.

  8. Integrated corridor management : phase I, concept development and foundational research. Task 3.4, identify integrated corridor management institutional strategies and administration

    Science.gov (United States)

    2006-04-12

    Task 3 involves overall foundational research to further the understanding of various aspects of Integrated Corridor Management (ICM) and to identify integration issues needed to evaluate the feasibility of the ICM initiative. The focus of Task 3.4 a...

  9. The application of business models to medical research: interviews with two founders of directed-philanthropy foundations. Interview with Scott Johnson and Don Listwin by Kathryn A. Phillips.

    Science.gov (United States)

    Scott, Johnson; Listwin, Don

    2007-01-01

    A new trend in research funding has emerged: directed philanthropy, in which the donor plays an active, hands-on role in managing the research by applying a "business model." Although such efforts now represent only a small portion of foundation funding, they have potentially far-reaching implications because (1) the approach of using a business model is being applied more broadly and (2) the success or failure of these efforts may portend the fate of larger translational efforts. The author conducted interviews with Scott Johnson of the Myelin Repair Foundation and Don Listwin of the Canary Foundation in the fall of 2006.

  10. From the 'Austrian Foundation for Atomic Energy Research' to the 'Seibersdorf Laboratories'

    International Nuclear Information System (INIS)

    Rößner, M.

    2013-01-01

    The aim of this thesis is the description of the process of institutionalization of nuclear research in Austria in the context of the „Atoms for Peace“ program in the 1950s. This aspect of the history of Austrian nuclear research has been relatively unexplored. The focus of this work is the presentation of measures that have been put in Austria to participate in the 'Atoms for Peace' program. Moreover, the expectations and goals of the Austrian nuclear program are analyzed. For this purpose, foundation, structure and research activities of the “Austrian Atomic Energy Commission”, the “Austrian Society for the Study of Atomic Energy” and the “Nuclear Reactor Centre Seibersdorf“ in the period from 1954 until about 1970 are examined. To establish a relationship with the international historical research of the history of nuclear research, the Austrian situation is compared to the Swiss and the German. It turns out that the Austrian expectations and objectives in nuclear research at the beginning of the period of observation roughly corresponded with the international trends. It also follows that by the establishment of the SGAE and the “Nuclear Reactor Centre Seibersdorf“ the development course of Austrian nuclear research occupied a special position compared to foreign institutions.(author) [de

  11. Grouting for Pile Foundation Improvement

    NARCIS (Netherlands)

    Van der Stoel, A.E.C.

    2001-01-01

    The aim of this research was to examine the use of grouting methods for pile foundation improvement, a generic term that is used here to define both foundation renovation (increasing the bearing capacity of a pile foundation that has insufficient bearing capacity) and foundation protection

  12. Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction

    Science.gov (United States)

    Stevens, Courtney; Pakulak, Eric; Hampton Wray, Amanda; Bell, Theodore A.; Neville, Helen J.

    2017-01-01

    This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds. PMID:28819066

  13. Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction.

    Science.gov (United States)

    Isbell, Elif; Stevens, Courtney; Pakulak, Eric; Hampton Wray, Amanda; Bell, Theodore A; Neville, Helen J

    2017-08-29

    This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds.

  14. Editorial research and the publication process in biomedicine and health: Report from the Esteve Foundation Discussion Group, December 2012

    Science.gov (United States)

    Marušić, Ana; Malički, Mario; von Elm, Erik

    2014-01-01

    Despite the fact that there are more than twenty thousand biomedical journals in the world, research into the work of editors and publication process in biomedical and health care journals is rare. In December 2012, the Esteve Foundation, a non-profit scientific institution that fosters progress in pharmacotherapy by means of scientific communication and discussion organized a discussion group of 7 editors and/or experts in peer review biomedical publishing. They presented findings of past editorial research, discussed the lack of competitive funding schemes and specialized journals for dissemination of editorial research, and reported on the great diversity of misconduct and conflict of interest policies, as well as adherence to reporting guidelines. Furthermore, they reported on the reluctance of editors to investigate allegations of misconduct or increase the level of data sharing in health research. In the end, they concluded that if editors are to remain gatekeepers of scientific knowledge they should reaffirm their focus on the integrity of the scientific record and completeness of the data they publish. Additionally, more research should be undertaken to understand why many journals are not adhering to editorial standards, and what obstacles editors face when engaging in editorial research. PMID:24969914

  15. Twists and turns in life and science. Foundation Series in Cancer Research

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Jan

    2008-01-01

    Roč. 99, č. 1 (2008), s. 1-32 ISSN 0065-230X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : cancer * oncogene * src Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.721, year: 2008

  16. Snapshots of what, exactly? A comment on methodological experimentation and conceptual foundations in place research

    Science.gov (United States)

    Daniel R. Williams; Michael E. Patterson

    2007-01-01

    Place ideas in natural resource management have grown in recent years. But with that growth have come greater complexity and diversity in thinking and mounting confusion about the ontological and epistemological assumptions underlying any specific investigation. Beckley et al. (2007) contribute to place research by proposing a new methodological approach to analyzing...

  17. Monsef Benkirane awarded 2013 Ming K. Jeang Foundation Retrovirology Prize: landmark HIV-1 research honoured

    NARCIS (Netherlands)

    Berkhout, Ben; Lever, Andrew; Wainberg, Mark; Fassati, Ariberto; Borrow, Persephone; Fujii, Masahiro

    2013-01-01

    Dr. Monsef Benkirane, from the Laboratoire de Virologie Moleculaire in Montpellier, France, has been announced as the recipient of the 2013 Retrovirology Prize. This bi-annual prize covers all aspects of the Retrovirology field and celebrates groundbreaking research from retrovirologists aged

  18. Constructivist Foundations of Intercultural Education: Implications for Research and Teacher Training

    Science.gov (United States)

    Leutwyler, Bruno; Petrovic, Danijela S.; Mantel, Carola

    2012-01-01

    Research uncovering different images of Intercultural Education seems to be relevant in various contexts. This paper describes and compares two, the Swiss and the Serbian contexts; two countries with very different histories and with very different political and social constellations. For the Swiss context, migration flows have changed…

  19. Evaluation of the Pilot Mentoring Program at the Research Foundation for SUNY

    Science.gov (United States)

    Henderson-Harr, Amy; Caggiano-Siino, Kathleen; Prewitt, Ashlee

    2016-01-01

    This article provides a description of an 18-month pilot program focused on the leadership development of the next generation of research administrators (RAs) in the State University of New York system (SUNY). The key questions for the evaluators were: 1) can we create a developmental program that effectively prepares the next generation of RAs;…

  20. Educational Quality in Music Teacher Education: Components of a Foundation for Research

    Science.gov (United States)

    Johansen, Geir

    2007-01-01

    Increasing demands for educational quality in higher education affect both higher music education and music teacher education. A theoretical framework is needed if we are to question what is meant by "educational quality" in the latter. To establish programs for quality development and assessment requires basic subject-specific research on the…

  1. 77 FR 63254 - Petition for Rulemaking Submitted by C-10 Research and Education Foundation, Inc.

    Science.gov (United States)

    2012-10-16

    ... Enclosure 1 of COMSECY-10-0007, research is needed to develop the safety basis for the behavior of high... Division 2 for concrete containments. While Section III, Division 3 of the ASME B&PV Code has been... and safe maintenance on a faulty or failing cask. The temperature of the fuel inside a dry storage...

  2. Oral Cancer Foundation

    Science.gov (United States)

    ... Get involved Understanding Dental Research People Resources About Understanding Events Get involved Dental Research Resources Contact Sitemap The Oral Cancer Foundation admin 2017-11-12T16:49:25+ ...

  3. Behaviour Guides and Law. Research Perspectives on the (InFormal and its Currently Shifting Foundations

    Directory of Open Access Journals (Sweden)

    Karin Harrasser / Elisabeth Timm

    2010-08-01

    Full Text Available The juridification of social life in the modern bourgeois world was long understood as a triumph of rationality over particular interests, as the “civilisation” of physical violence. For some time now, this grand narrative of the modern world has been criticized as a specific historical case, as Eurocentric and bourgeois. Additionally, the concept and practice of modern, national sovereign statehood is being challenged in many ways. Individuals are also experiencing an unbounding of their “sovereignty”. The article sums up different disciplines’ research into the fields of behaviour guides and law. In doing so, it sketches out research perspectives intended to transcend the either-or dichotomy of the previous debates (ethics / particular / informal / personal / emotional-cultural vs. law / universal / formal / institutional and envisions new analytical assessments of these two poles.

  4. Dialectical and historical materialism as the foundation of educational research in Cuba

    Directory of Open Access Journals (Sweden)

    Luís Mijares Núñez

    2006-06-01

    Full Text Available This article presents an analysis about the need of understanding the meaning and methodological implications in theory as well as in practice of the dialectical and historical materialistic method for the process of scientific research in the educational field. It also presents the reducing character of the quantitative, positive, qualitative or interpretative paradigms and the positions of Marxism Leninism regarding data and their multi methodological character.

  5. Dialectical and historical materialism as the foundation of educational research in Cuba

    OpenAIRE

    Luís Mijares Núñez

    2006-01-01

    This article presents an analysis about the need of understanding the meaning and methodological implications in theory as well as in practice of the dialectical and historical materialistic method for the process of scientific research in the educational field. It also presents the reducing character of the quantitative, positive, qualitative or interpretative paradigms and the positions of Marxism Leninism regarding data and their multi methodological character.

  6. Alkylating Agent-Induced NRF2 Blocks Endoplasmic Reticulum Stress-Mediated Apoptosis via Control of Glutathione Pools and Protein Thiol Homeostasis.

    Science.gov (United States)

    Zanotto-Filho, Alfeu; Masamsetti, V Pragathi; Loranc, Eva; Tonapi, Sonal S; Gorthi, Aparna; Bernard, Xavier; Gonçalves, Rosângela Mayer; Moreira, José C F; Chen, Yidong; Bishop, Alexander J R

    2016-12-01

    Alkylating agents are a commonly used cytotoxic class of anticancer drugs. Understanding the mechanisms whereby cells respond to these drugs is key to identify means to improve therapy while reducing toxicity. By integrating genome-wide gene expression profiling, protein analysis, and functional cell validation, we herein demonstrated a direct relationship between NRF2 and Endoplasmic Reticulum (ER) stress pathways in response to alkylating agents, which is coordinated by the availability of glutathione (GSH) pools. GSH is essential for both drug detoxification and protein thiol homeostasis within the ER, thus inhibiting ER stress induction and promoting survival, an effect independent of its antioxidant role. NRF2 accumulation induced by alkylating agents resulted in increased GSH synthesis via GCLC/GCLM enzyme, and interfering with this NRF2 response by either NRF2 knockdown or GCLC/GCLM inhibition with buthionine sulfoximine caused accumulation of damaged proteins within the ER, leading to PERK-dependent apoptosis. Conversely, upregulation of NRF2, through KEAP1 depletion or NRF2-myc overexpression, or increasing GSH levels with N-acetylcysteine or glutathione-ethyl-ester, decreased ER stress and abrogated alkylating agents-induced cell death. Based on these results, we identified a subset of lung and head-and-neck carcinomas with mutations in either KEAP1 or NRF2/NFE2L2 genes that correlate with NRF2 target overexpression and poor survival. In KEAP1-mutant cancer cells, NRF2 knockdown and GSH depletion increased cell sensitivity via ER stress induction in a mechanism specific to alkylating drugs. Overall, we show that the NRF2-GSH influence on ER homeostasis implicates defects in NRF2-GSH or ER stress machineries as affecting alkylating therapy toxicity. Mol Cancer Ther; 15(12); 3000-14. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: issues and recommendations. A Rome Foundation working team report.

    Science.gov (United States)

    Sperber, A D; Gwee, K A; Hungin, A P; Corazziari, E; Fukudo, S; Gerson, C; Ghoshal, U C; Kang, J-Y; Levy, R L; Schmulson, M; Dumitrascu, D; Gerson, M-J; Chen, M; Myung, S-J; Quigley, E M M; Whorwell, P J; Zarzar, K; Whitehead, W E

    2014-11-01

    Cross-cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross-cultural comparative research can make a significant contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra-intestinal co-morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health-related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race. To identify methodological challenges for cross-cultural, multinational research, and suggest possible solutions. This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion. Cross-cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results. Advances in study design and methodology, as well as cross-cultural research competence, have not matched technological advancements. The development of multinational research networks and cross-cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting. © 2014 John Wiley & Sons Ltd.

  8. Complex Intelligent Systems: Juxtaposition of Foundational Notions and a Research Agenda

    Directory of Open Access Journals (Sweden)

    Petros A.M. Gelepithis

    2001-12-01

    Full Text Available Abstract: The cardinality of the class, C , of complex intelligent systems, i.e., systems of intelligent systems and their resources, is steadily increasing. Such an increase, whether designed, sometimes changes significantly and fundamentally, the structure of C . Recently,the study of members of C and its structure comes under a variety of multidisciplinary headings the most prominent of which include General Systems Theory, Complexity Science, Artificial Life, and Cybernetics. Their common characteristic is the quest for a unified theory of a certain class of systems like a living system or an organisation. So far, the only candidate for a general theory of intelligent systems is Newell's Soar. To my knowledge there is presently no candidate theory of C except Newell's claimed extensibility of Soar. This paper juxtaposes the elements of Newell's conceptual basis with those of an alternative conceptual framework based on the thesis that communication and understanding are the primary processes shaping the structure of C and its members. It is patently obvious that a research agenda for the study of C can be extremely varied and long. The third section of this paper presents a highly selective research agenda that aims to provoke discussion among complexity theory scientists.

  9. American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection: Overview of a powerful tool for orthodontic research and teaching.

    Science.gov (United States)

    Baumrind, Sheldon; Curry, Sean

    2015-08-01

    This article reports on the current status of the American Association of Orthodontists Foundation (AAOF) Craniofacial Growth Legacy Collection--an AAOF-supported multi-institutional project that uses the Internet and cloud computing to collect and share craniofacial images and data for orthodontic research and education. The project gives investigators and clinicians all over the world online access to longitudinal information on craniofacial development in untreated children with malocclusions of various types. It also is a unique source of control samples for testing the validity of consensually accepted beliefs about the effects of orthodontic treatment or of failure to treat. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  10. World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: I. Surgical phenotype data collection in endometriosis research

    DEFF Research Database (Denmark)

    Becker, Christian M.; Laufer, Marc R.; Stratton, Pamela

    2014-01-01

    ObjectiveTo standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition.......ObjectiveTo standardize the recording of surgical phenotypic information on endometriosis and related sample collections obtained at laparoscopy, allowing large-scale collaborative research into the condition....

  11. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research

    DEFF Research Database (Denmark)

    Vitonis, Allison F.; Vincent, Katy; Rahmioglu, Nilufer

    2014-01-01

    ObjectiveTo harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration.......ObjectiveTo harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration....

  12. 31 March 2016 - Qatar Foundation Research and Development Executive Vice President H. Al-Ibrahim signing a Cooperation Agreement with CERN Director-General F. Gianotti.

    CERN Multimedia

    Brice, Maximilien

    2016-01-01

    Dr Hamad Al-Ibrahim Executive Vice President, Qatar Foundation Research and Development. Were present: CERN International Relations Unit, Adviser for Qatar P. Fassnacht; CERN Director for Research and Computing E. Elsen; Texas A&M Professor of Physics A. Safonov ; CERN Director for International Relations C. Warakaulle; Professor of Physics, Qatar University I.Al-Qaradawi; Executive Vice President H. Al-Ibrahim; CERN Director-General F. Gianotti; Ambassador Faisal Bin Abdulla Al-Henzab to the UNOG; Director of Research Computing, Texas A&M, Qatar O. Bouhali; Vice Dean, Texas A&M, Qatar E. Massad; Executive Director, Research Coordination & Special Initiatives, Qatar Foundation R&D D. Khoury.

  13. HSC Foundation

    Science.gov (United States)

    ... in disability information or services and that add value to our existing programs. The Foundation also works to bring additional support to initiatives by serving as funding partners on projects that have local impact and national relevance. Supporting a Continuum of Care The HSC Foundation ...

  14. 15th March 2011 - Singapore National Research Foundation Permanent Secretary(National Research and Development)T. M. Kian signing the guest book with Head of International Relations F. Pauss and visiting CMS control centre with Collaboration Spokesperson G. Tonelli.

    CERN Multimedia

    Maximilien Brice

    2011-01-01

    15th March 2011 - Singapore National Research Foundation Permanent Secretary(National Research and Development)T. M. Kian signing the guest book with Head of International Relations F. Pauss and visiting CMS control centre with Collaboration Spokesperson G. Tonelli.

  15. Activities of the National Academy of Sciences in relation to the Radiation Effects Research Foundation

    Energy Technology Data Exchange (ETDEWEB)

    Edington, C.W.

    1992-06-01

    This progress report relates progress in the various research projects evaluating the late health effects, both somatic and genetic, resulting from radiation exposure of the survivors of the atomic bombs at Hiroshima and Nagasaki, Japan. Considerable progress has been made in the collection and utilization of the various epidemiological data bases. These include the Life Span Study, (LSS) cohort, the Adult Health Study (AHS) cohort, the In Utero cohort, the leukemia registry and the F-1 Study population. Important progress has been made in using RERF Tumor and Tissue Registry records for evaluation of cancer incidence and radiation risk estimates for comparison with cancer mortality and risk in the LSS cohort. At the present time, a manuscript on the incidence of solid tumors (1950-1987) is undergoing internal and external review for publication as an RERF Technical report (TR) and for publication in a peer-reviewed scientific journal. In addition, manuscripts are in preparation on (1) a comprehensive report on the incidence of hematological cancers, including analysis of leukemia by cell type (1950-1987), (2) a general description of Tumor Registry operations and (3) a comparison of incidence- and mortality-based estimates of radiation risk in the LSS cohort.

  16. [Research progresses of the completed pediatrics projects funded by National Natural Science Foundation of China from 2002 to 2006].

    Science.gov (United States)

    Xu, Ling; Hao, Jie; Deng, Min; Xu, Yan-ying

    2009-05-01

    To understand the projects completion and research progresses in pediatrics which were funded by the National Natural Science Foundation of China (NSFC), and evaluate the accomplishment objectively and justly. The completion status of projects in pediatrics funded by department of clinical medicine II from 2002 to 2006 was analysed retrospectively, and important research achievement and outstanding development in some projects were reported. During the period between 2002 and 2006, 420 articles were published, and the average was 8.1 papers per project, which included 56 papers that were published in journals indexed by SCI (the average was 1.1 papers per project). The completion of general project was better than that of "the Young Researchers Fund" and small grant project. Ten post-doctors, 102 doctors and 109 masters were trained. Two projects were awarded with the first grade prize and another 2 with the second grade prize at the provincial and ministerial level, 4 items applied for patent and 1 was granted. These completed projects, which were mainly related to 7 of 12 subspecialties in the field of pediatrics, such as the respiratory disease, nephrology, neurology, cardiology, endocrinology, hematology, neonatology, are the major portion of the application projects and subsidized projects funded by NSFC, and achieved great research progresses. During the period between 2002 and 2006, the 52 completed projects in pediatrics showed difference in the distribution and quality of accomplishment among subspecialties and among types of supported projects; there are some gaps between pediatrics and some other clinical basic subspecialties II, this situation released the research status and problems in development of pediatrics in China. The general projects completion was good, and many projects obtained research achievements, which reflect the leading function of NSFC in pediatric research.

  17. Use of reinforced soil foundation (RSF) to support shallow foundation.

    Science.gov (United States)

    2008-11-01

    The main objective of this research study is to investigate potential benefits of using the reinforced soil foundations to improve the bearing capacity and to reduce the settlement of shallow foundations on soils. This includes examining influences o...

  18. The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC case register: development and descriptive data

    Directory of Open Access Journals (Sweden)

    Denis Mike

    2009-08-01

    Full Text Available Abstract Background Case registers have been used extensively in mental health research. Recent developments in electronic medical records, and in computer software to search and analyse these in anonymised format, have the potential to revolutionise this research tool. Methods We describe the development of the South London and Maudsley NHS Foundation Trust (SLAM Biomedical Research Centre (BRC Case Register Interactive Search tool (CRIS which allows research-accessible datasets to be derived from SLAM, the largest provider of secondary mental healthcare in Europe. All clinical data, including free text, are available for analysis in the form of anonymised datasets. Development involved both the building of the system and setting in place the necessary security (with both functional and procedural elements. Results Descriptive data are presented for the Register database as of October 2008. The database at that point included 122,440 cases, 35,396 of whom were receiving active case management under the Care Programme Approach. In terms of gender and ethnicity, the database was reasonably representative of the source population. The most common assigned primary diagnoses were within the ICD mood disorders (n = 12,756 category followed by schizophrenia and related disorders (8158, substance misuse (7749, neuroses (7105 and organic disorders (6414. Conclusion The SLAM BRC Case Register represents a 'new generation' of this research design, built on a long-running system of fully electronic clinical records and allowing in-depth secondary analysis of both numerical, string and free text data, whilst preserving anonymity through technical and procedural safeguards.

  19. Foundation Structure

    DEFF Research Database (Denmark)

    2009-01-01

    Method of installing a bucket foundation structure comprising one, two, three or more skirts, into soils in a controlled manner. The method comprises two stages: a first stage being a design phase and the second stage being an installation phase. In the first stage, design parameters are determined...... relating to the loads on the finished foundation structure; soil profile on the location; allowable installation tolerances, which parameters are used to estimate the minimum diameter and length of the skirts of the bucket. The bucket size is used to simulate load situations and penetration into foundation...

  20. World Endometriosis Research Foundation Endometriosis Phenome and biobanking harmonization project: II. Clinical and covariate phenotype data collection in endometriosis research

    Science.gov (United States)

    Vitonis, Allison F.; Vincent, Katy; Rahmioglu, Nilufer; Fassbender, Amelie; Buck Louis, Germaine M.; Hummelshoj, Lone; Giudice, Linda C.; Stratton, Pamela; Adamson, G. David; Becker, Christian M.; Zondervan, Krina T.; Missmer, Stacey A.

    2014-01-01

    Objective To harmonize the collection of nonsurgical clinical and epidemiologic data relevant to endometriosis research, allowing large-scale collaboration. Design An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents. Setting In 2013, two workshops followed by global consultation, bringing together 54 leaders in endometriosis research. Patients None. Intervention(s) Development of a self-administered endometriosis patient questionnaire (EPQ), based on [1] systematic comparison of questionnaires from eight centers that collect data from endometriosis cases (and controls/comparison women) on a medium to large scale (publication on >100 cases); [2] literature evidence; and [3] several global consultation rounds. Main Outcome Measure(s) Standard recommended and minimum required questionnaires to capture detailed clinical and covariate data. Result(s) The standard recommended (EPHect EPQ-S) and minimum required (EPHect EPQ-M) questionnaires contain questions on pelvic pain, subfertility and menstrual/reproductive history, hormone/medication use, medical history, and personal information. Conclusion(s) The EPQ captures the basic set of patient characteristics and exposures considered by the WERF EPHect Working Group to be most critical for the advancement of endometriosis research, but is also relevant to other female conditions with similar risk factors and/or symptomatology. The instruments will be reviewed based on feedback from investigators, and–after a first review after 1 year–triannually through systematic follow-up surveys. Updated versions will be made available through http://endometriosisfoundation.org/ephect. PMID:25256930

  1. Examining the Extent and Nature of Online Learning in American K-12 Education: The Research Initiatives of the Alfred P. Sloan Foundation

    Science.gov (United States)

    Picciano, Anthony G.; Seaman, Jeff; Shea, Peter; Swan, Karen

    2012-01-01

    In 1992, the Alfred P. Sloan Foundation began its "Anytime, Anyplace Learning Program", the purpose of which was to explore educational alternatives for people who wanted to pursue an education via Internet technology. Part of this grant activity was a research award to the Babson College Survey Research Group to examine online learning in…

  2. Glaucoma Research Foundation

    Science.gov (United States)

    ... born with glaucoma. Read her story » Learn About Glaucoma Glaucoma is a complicated disease in which damage ... Christopher doesn't ever want to go blind » Glaucoma 360 Glaucoma 360 — three days of events uniting ...

  3. Kessler Foundation Research Center

    Science.gov (United States)

    ... with a holistic assessment of students’ values, interests, personalities, and aptitudes. Read More -> Kessler Foundation’s Blog Caring ... Expanding Inclusion of People with Disabilities in the Workplace nTIDE September 2017 Jobs Report: Economic Recovery Extends ...

  4. Scleroderma Research Foundation

    Science.gov (United States)

    ... will continue. Learn more The SRF: A Four Star Charity The SRF has achieved the highest possible ... Saget share about his connection to scleroderma and what he is doing to make a difference. Click ...

  5. Vasculitis Foundation

    Science.gov (United States)

    ... Our Board Our Team Anniversary Vasculitis Foundation Newsletters Annual Reports Press Page Literature Order Form Join Contact Us Dream Big Donate Donate Support the VF Through the Amazon Smile Program United Way Giving Ways to Give ...

  6. Marfan Foundation

    Science.gov (United States)

    ... The Marfan Foundation Marfan & Related Disorders What is Marfan Syndrome? What are Related Disorders? What are the Signs? ... Click to see what's happening around the country! Marfan syndrome is a life-threatening genetic disorder, and an ...

  7. CARES Foundation

    Science.gov (United States)

    ... Foundation Video Get Involved EMS and Newborn Screening campaigns Clincal trials Fundraisers Support groups Connect and promote with Social Media: Facebook , Twitter , Instagram and LinkedIn News & Notes from ...

  8. Children's Brain Tumor Foundation

    Science.gov (United States)

    ... 2 Family Donate Volunteer Justin's Hope Fund Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  9. National Psoriasis Foundation

    Science.gov (United States)

    ... 723-9166 | Submit a Question | Learn More National Psoriasis Foundation provides you with the help you need to best manage your psoriasis or psoriatic arthritis, while promoting research to find ...

  10. International OCD Foundation

    Science.gov (United States)

    ... and productive lives. Join Donate Volunteer Events International OCD Foundation Research. Resources. Respect. About OCD About IOCDF ... Donate Here Why Should You Attend the Annual OCD Conference? Watch the Video Find Help Search the ...

  11. Mars Exploration Student Data Teams: Building Foundations and Influencing Students to Pursue STEM Careers through Experiences with Authentic Research

    Science.gov (United States)

    Turney, D.; Grigsby, B.; Murchie, S. L.; Buczkowski, D.; Seelos, K. D.; Nair, H.; McGovern, A.; Morgan, F.; Viviano, C. E.; Goudge, T. A.; Thompson, D.

    2013-12-01

    The Mars Exploration Student Data Teams (MESDT) immerses diverse teams of high school and undergraduate students in an authentic research Science, Technology, Engineering and Mathematics (STEM) based experience and allows students to be direct participants in the scientific process by working with scientists to analyze data sets from NASA's Mars program, specifically from the CRISM instrument. MESDT was created by Arizona State University's Mars Education Program, and is funded through NASA's Compact Reconnaissance Imaging Spectrometer for Mars or CRISM, an instrument onboard the Mars Reconnaissance Orbiter (MRO). Students work with teacher mentors and CRISM team members to analyze data, develop hypotheses, conduct research, submit proposals, critique and revise work. All students begin the program with basic Mars curriculum lessons developed by the MESDT education team. This foundation enables the program to be inclusive of all students. Teachers have reported that populations of students with diverse academic needs and abilities have been successful in this program. The use of technology in the classroom allows the MESDT program to successfully reach a nationwide audience and funding provided by NASA's CRISM instrument allows students to participate free of charge. Recent changes to the program incorporate a partnership with United States Geological Survey (USGS) and a CRISM sponsored competitive scholarship for two teams of students to present their work at the annual USGS Planetary Mappers Meeting. Returning MESDT teachers have attributed an increase in student enrollment and interest to this scholarship opportunity. The 2013 USGS Planetary Mappers Meeting was held in Washington DC which provided an opportunity for the students to meet with their Senators at the US Capitol to explain the science work they had done throughout the year as well as the impact that the program had had on their goals for the future. This opportunity extended to the students by the

  12. Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation.

    Science.gov (United States)

    Pokhrel, Subhash; Reidpath, Daniel; Allotey, Pascale

    2011-01-06

    The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD) control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF) - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. Of 67 projects analysed, 26 projects (39%) were social science related while 41 projects (61%) were basic science or other translational research including drug development. A total of US$ 697 million was spent to fund the projects, of which 35% ((US$ 241 million) went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research.

  13. Social sciences research in neglected tropical diseases 3: Investment in social science research in neglected diseases of poverty: a case study of Bill and Melinda Gates Foundation

    Directory of Open Access Journals (Sweden)

    Reidpath Daniel

    2011-01-01

    Full Text Available Abstract Background The level of funding provides a good proxy for the level of commitment or prioritisation given to a particular issue. While the need for research relevant to social, economic, cultural and behavioural aspects of neglected tropical diseases (NTD control has been acknowledged, there is limited data on the level of funding that supports NTD social science research. Method A case study was carried out in which the spending of a major independent funder, the Bill and Melinda Gates Foundation (BMGF - was analysed. A total of 67 projects funded between October 1998 and November 2008 were identified from the BMGF database. With the help of keywords within the titles of 67 grantees, they were categorised as social science or non-social science research based on available definition of social science. A descriptive analysis was conducted. Results Of 67 projects analysed, 26 projects (39% were social science related while 41 projects (61% were basic science or other translational research including drug development. A total of US$ 697 million was spent to fund the projects, of which 35% ((US$ 241 million went to social science research. Although the level of funding for social science research has generally been lower than that for non-social science research over 10 year period, social science research attracted more funding in 2004 and 2008. Conclusion The evidence presented in this case study indicates that funding on NTD social science research compared to basic and translational research is not as low as it is perceived to be. However, as there is the acute need for improved delivery and utilisation of current NTD drugs/technologies, informed by research from social science approaches, funding priorities need to reflect the need to invest significantly more in NTD social science research.

  14. Nrf2 activation prevents cadmium-induced acute liver injury

    International Nuclear Information System (INIS)

    Wu, Kai C.; Liu, Jie J.; Klaassen, Curtis D.

    2012-01-01

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H 2 DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice were

  15. Nrf2 activation prevents cadmium-induced acute liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Kai C. [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Liu, Jie J. [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS (United States)

    2012-08-15

    Oxidative stress plays an important role in cadmium-induced liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that up-regulates cytoprotective genes in response to oxidative stress. To investigate the role of Nrf2 in cadmium-induced hepatotoxicity, Nrf2-null mice, wild-type mice, kelch-like ECH-associated protein 1-knockdown (Keap1-KD) mice with enhanced Nrf2, and Keap1-hepatocyte knockout (Keap1-HKO) mice with maximum Nrf2 activation were treated with cadmium chloride (3.5 mg Cd/kg, i.p.). Blood and liver samples were collected 8 h thereafter. Cadmium increased serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activities, and caused extensive hepatic hemorrhage and necrosis in the Nrf2-null mice. In contrast, Nrf2-enhanced mice had lower serum ALT and LDH activities and less morphological alternations in the livers than wild-type mice. H{sub 2}DCFDA (2′,7′-dichlorodihydrofluoresein diacetate) staining of primary hepatocytes isolated from the four genotypes of mice indicated that oxidative stress was higher in Nrf2-null cells, and lower in Nrf2-enhanced cells than in wild-type cells. To further investigate the mechanism of the protective effect of Nrf2, mRNA of metallothionein (MT) and other cytoprotective genes were determined. Cadmium markedly induced MT-1 and MT-2 in livers of all four genotypes of mice. In contrast, genes involved in glutathione synthesis and reducing reactive oxygen species, including glutamate-cysteine ligase (Gclc), glutathione peroxidase-2 (Gpx2), and sulfiredoxin-1 (Srxn-1) were only induced in Nrf2-enhanced mice, but not in Nrf2-null mice. In conclusion, the present study shows that Nrf2 activation prevents cadmium-induced oxidative stress and liver injury through induction of genes involved in antioxidant defense rather than genes that scavenge Cd. -- Highlights: ► Cadmium caused extensive hepatic hemorrhage and necrosis in Nrf2-null mice. ► Keap1-KD and Keap1-HKO mice

  16. Evaluating health inequity interventions: applying a contextual (external) validity framework to programs funded by the Canadian Health Services Research Foundation.

    Science.gov (United States)

    Phillips, Kaye; Müller-Clemm, Werner; Ysselstein, Margaretha; Sachs, Jonathan

    2013-02-01

    Including context in the measurement and evaluation of health in equity interventions is critical to understanding how events that occur in an intervention's environment might contribute to or impede its success. This study adapted and piloted a contextual validity assessment framework on a selection of health inequity-related programs funded by the Canadian Health Services Research Foundation (CHSRF) between 1998 and 2006. The two overarching objectives of this study were (1) to determine the relative amount and quality of attention given to conceptualizing, measuring and validating context within CHSRF funded research final reports related to health-inequity; and (2) to contribute evaluative evidence towards the incorporation of context into the assessment and measurement of health inequity interventions. The study found that of the 42/146 CHSRF programs and projects, judged to be related to health inequity 20 adequately reported on the conceptualization, measurement and validation of context. Amongst these health-inequity related project reports, greatest emphasis was placed on describing the socio-political and economical context over actually measuring and validating contextual evidence. Applying a contextual validity assessment framework was useful for distinguishing between the descriptive (conceptual) versus empirical (measurement and validation) inclusion of documented contextual evidence. Although contextual validity measurement frameworks needs further development, this study contributes insight into identifying funded research related to health inequities and preliminary criteria for assessing interventions targeted at specific populations and jurisdictions. This study also feeds a larger critical dialogue (albeit beyond the scope of this study) regarding the relevance and utility of using evaluative techniques for understanding how specific external conditions support or impede the successful implementation of health inequity interventions. Copyright

  17. Large scale seismic test research at Hualien site in Taiwan. Results of site investigation and characterization of the foundation ground

    International Nuclear Information System (INIS)

    Okamoto, Toshiro; Kokusho, Takeharu; Nishi, Koichi

    1998-01-01

    An international joint research program called ''HLSST'' is under way. Large-Scale Seismic Test (LSST) is to be conducted to investigate Soil-Structure Interaction (SSI) during large earthquakes in the field in Hualien, a high seismic region in Taiwan. A 1/4-scale model building was constructed on the excavated gravelly ground, and the backfill material of crushed stones was placed around the model plant. The model building and the foundation ground were extensively instrumented to monitor structure and ground response. To accurately evaluate SSI during earthquakes, geotechnical investigation and forced vibration test were performed during construction process namely before/after the base excavation, after the structure construction and after the backfilling. Main results are as follows. (1) The distribution of the mechanical properties of the gravelly soil are measured by various techniques including penetration tests and PS-logging and it found that the shear wave velocities (Vs) change clearly and it depends on changing overburden pressures during the construction process. (2) Measuring Vs in the surrounding soils, it found that the Vs is smaller than that at almost same depth in the farther location. Discussion is made further on the numerical soil model for SSI analysis. (author)

  18. Theoretical Foundations of Research Focused on HIV Prevention Among Substance-Involved Women: A Review of Observational and Intervention Studies.

    Science.gov (United States)

    Auerbach, Judith D; Smith, Laramie R

    2015-06-01

    Although substance use continues to be a significant component of HIV risk among women worldwide, to date, relatively little attention has been paid in research, services, or policy to substance-involved women (SIW). HIV acquisition for SIW stems from transmission risks directly related to substance use and risks associated with sexual activity in which power to negotiate risk and safety are influenced by dynamics of male partnerships, sex work, and criminalization (of both drug use and sex work), among other factors. As such, HIV risk for SIW resides as much in the environment—physical, social, cultural, economic, and political—in which drug use occurs as it does from transmission-related behaviors of individual women. To reduce HIV infections among SIW, it is important to specify the interaction of individual- and environmental-level factors, including, but not limited to those related to women's own substance use, that can and ought to be changed. This involves theorizing about the interplay of gender, substance use, and HIV risk, and incorporating that theoretical understanding into intervention design and evaluation. A review of the published literature focused on HIV prevention among SIW revealed a general lack of theoretical and conceptual foundation specific to the gender-related and environmental drivers of HIV in this population. Greater theoretical linkages to intersectionality and syndemic approaches are recommended to better identify and target relevant mechanisms by which the interplay of gender dynamics and substance use potentiate the likelihood of HIV acquisition and transmission among SIW.

  19. Cancer risk among children of atomic bomb survivors. A review of RERF epidemiologic studies. Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    Yoshimoto, Y.

    1990-01-01

    This article summarizes recent epidemiologic studies of cancer risk among the children of atomic bomb survivors conducted at the Radiation Effects Research Foundation. These children include two groups: (1) the in utero-exposed children (ie, those born to mothers who had been pregnant at the time of the bombings of Hiroshima and Nagasaki) and (2) the F1 population, which was conceived after the atomic-bombings and born to parents of whom one or both were atomic bomb survivors. Although from 1950 to 1984 only 18 cancer cases were identified among the in utero sample, cancer risk did appear to significantly increase as maternal uterine dose increased. However, since the observed cases are too few in number to allow a site-specific review, the increased cancer risk cannot be definitively attributed to atomic bomb radiation, as yet. For those members of the F1 population who were less than 20 years old between 1946 and 1982, cancer risk did not appear to increase significantly as parental gonadal dose increased. Follow-up of this population will continue to determine if the patterns of adult-onset cancer are altered

  20. Measurement of magnetic susceptibility on tailings cores report on cores obtained from the Ontario Research Foundation lysimeter experiment

    International Nuclear Information System (INIS)

    1984-10-01

    Bulk susceptibility and induced magnetic remanence results are reported for 40 cores obtained from the uranium tailings lysimeter experiment at the Ontario Research Foundation. Both methods indicate a broad threefold subdivision of the tailings pile. An upper zone is characterized by an enhanced susceptibility level, which is related to enhanced concentration of both magnetite and hematite. Depletion zones, where present, are of limited areal extent and strongly developed. An intermediate zone is characterized by a mixture of large areas of reduced susceptibility that separate smaller regions of slightly enhanced susceptibility. The zones of susceptibility depletion appear to define a dendritic drainage pattern. Locally in this zone magnetite is enhanced and hematite depleted. In the lowermost zone susceptibility levels are reduced over most of the tailings bed. Only in the upper most right hand corner is there any vestige of a positive susceptibility concentration. Both magnetite and hematite are strongly depleted in this lower zone. Visually it is apparent that this lowermost depleted zone correlates to the zones of strongest 'yellowcake' development

  1. Global faculty development: lessons learned from the Foundation for Advancement of International Medical Education and Research (FAIMER) initiatives.

    Science.gov (United States)

    Burdick, William P

    2014-08-01

    Foundation for Advancement of International Medical Education and Research (FAIMER) faculty development programs have operated since 2001 and are designed to overcome many of the challenges inherent in global health collaborations, including alignment with local needs, avoiding persistent dependency, and development of trust. FAIMER fellowship programs, developed for midcareer faculty members in all health professions from around the world, share goals of strengthening knowledge and skills in education leadership, education methods, and project management and evaluation. Building community is another explicit goal that allows participants to support and learn from each other.The author recommends several practices for successful international collaborations based on 13 years of experience with FAIMER fellowships. These include using authentic education projects to maintain alignment with local needs and apply newly acquired knowledge and skills, teaching leadership across cultures with careful communication and adaptation of concepts to local environments, cultivating a strong field of health professions education to promote diffusion of ideas and advocate for policy change, intentionally promoting field development and leadership to reduce dependency, giving generously of time and resources, learning from others as much as teaching others, and recognizing that effective partnerships revolve around personal relationships to build trust. These strategies have enabled the FAIMER fellowship programs to stay aligned with local needs, reduce dependency, and maintain trust.

  2. 'The industry must be inconspicuous': Japan Tobacco's corruption of science and health policy via the Smoking Research Foundation.

    Science.gov (United States)

    Iida, Kaori; Proctor, Robert N

    2018-02-04

    To investigate how and why Japan Tobacco, Inc. (JT) in 1986 established the Smoking Research Foundation (SRF), a research-funding institution, and to explore the extent to which SRF has influenced science and health policy in Japan. We analysed documents in the Truth Tobacco Industry Documents archive, along with recent Japanese litigation documents and published documents. JT's effort to combat effective tobacco control was strengthened in the mid-1980s, following privatisation of the company. While remaining under the protection of Japan's Ministry of Finance, the semiprivatised company lost its 'access to politicos', opening up a perceived need for collaboration with global cigarette makers. One solution, arrived at through clandestine planning with American companies, was to establish a third-party organisation, SRF, with the hope of capturing scientific and medical authority for the industry. Guarded by powerful people in government and academia, SRF was launched with the covert goal of influencing tobacco policy both inside and outside Japan. Scholars funded by SRF have participated in international conferences, national advisory committees and tobacco litigation, in most instances helping the industry to maintain a favourable climate for the continued sale of cigarettes. Contrary to industry claims, SRF was never meant to be independent or neutral. With active support from foreign cigarette manufacturers, SRF represents the expansion into Asia of the denialist campaign that began in the USA in 1953. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. American Indians and Minnesota's Private Colleges. An Evaluation of the Minnesota Private College Research Foundation's Indian Education Project, 1971-72 -- 1974-75.

    Science.gov (United States)

    Panitz, Emanuel

    The Minnesota Private College Research Foundation - Indian Education Project (MPCRF-IEP) provided additional financial support for programs that were unique, developmental, and Indian in their approach to expansion of higher educational opportunities for Native American students. Funding allocated by the Project was made on a dollar for dollar…

  4. Arthritis Foundation

    Science.gov (United States)

    ... Vision Leadership News Partners & Sponsors Careers Code of Ethics Financials Annual Report Contact Us Privacy Policy Terms & Conditions Donate Press Store Blog Community Local Offices Kids Get Arthritis Too Español Arthritis Today Social Media Newsletters Sign Up for E-Newsletters Arthritis Foundation ...

  5. Foundations of measurement

    CERN Document Server

    Suppes, Patrick

    1989-01-01

    Foundations of Measurement offers the most coherently organized treatment of the topics and issues central to measurement. Much of the research involved has been scattered over several decades and a multitude of journals--available in many instances only to specialties. With the publication of Volumes two and three of this important work, Foundations of Measurement is the most comprehensive presentation in the area of measurement.

  6. Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Madhurima; Kwong, Erick K.; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y., E-mail: jchan@uci.edu

    2013-08-01

    Nuclear factor E2-related factor-1 (Nrf1) is a basic leucine zipper transcription factor that is known to regulate antioxidant and cytoprotective gene expression. It was recently shown that Nrf1 is regulated by SCF–Fbw7 ubiquitin ligase. However our knowledge of upstream signals that targets Nrf1 for degradation by the UPS is not known. We report here that Nrf1 expression is negatively regulated by glycogen synthase kinase 3 (GSK3) in Fbw7-dependent manner. We show that GSK3 interacts with Nrf1 and phosphorylates the Cdc4 phosphodegron domain (CPD) in Nrf1. Mutation of serine residue in the CPD of Nrf1 to alanine (S350A), blocks Nrf1 from phosphorylation by GSK3, and stabilizes Nrf1. Knockdown of Nrf1 and expression of a constitutively active form of GSK3 results in increased apoptosis in neuronal cells in response to ER stress, while expression of the GSK3 phosphorylation resistant S350A–Nrf1 attenuates apoptotic cell death. Together these data suggest that GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. Highlights: • The effect of GSK3 on Nrf1 expression was examined. • GSK3 destabilizes Nrf1 protein via Fbw7 ubiquitin ligase. • GSK3 binds and phosphorylates Nrf1. • Protection from stress-induced apoptosis by Nrf1 is inhibited by GSK3.

  7. Effects of Nrf2 deficiency on arsenic metabolism in mice.

    Science.gov (United States)

    Wang, Huihui; Zhu, Jiayu; Li, Lu; Li, Yongfang; Lv, Hang; Xu, Yuanyuan; Sun, Guifan; Pi, Jingbo

    2017-12-15

    Inorganic arsenic (iAs) is a known toxicant and carcinogen. Worldwide arsenic exposure has become a threat to human health. The severity of arsenic toxicity is strongly correlated with the speed of arsenic metabolism (methylation) and clearance. Furthermore, oxidative stress is recognized as a major mechanism for arsenic-induced toxicity. Nuclear factor-E2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, is clearly involved in alleviation of arsenic-induced oxidative damage. Multiple studies demonstrate that Nrf2 deficiency mice are more vulnerable to arsenic-induced intoxication. However, what effect Nrf2 deficiency might have on arsenic metabolism in mice is still unknown. In the present study, we measured the key enzymes involved in arsenic metabolism in Nrf2-WT and Nrf2-KO mice. Our results showed that basal transcript levels of glutathione S-transferase omega 2 (Gsto2) were significantly higher and GST mu 1 (Gstm1) lower in Nrf2-KO mice compared to Nrf2-WT control. Arsenic speciation and methylation rate in liver and urine was then studied in mice treated with 5mg/kg sodium arsenite for 12h. Although there were some alterations in arsenic metabolism enzymes between Nrf2-WT and Nrf2-KO mice, the Nrf2 deficiency had no significant effect on arsenic methylation. These results suggest that the Nrf2-KO mice are more sensitive to arsenic than Nrf2-WT mainly because of differences in adaptive antioxidant detoxification capacity rather than arsenic methylation capacity. Copyright © 2017. Published by Elsevier Inc.

  8. Translational control of Nrf2 within the open reading frame

    International Nuclear Information System (INIS)

    Perez-Leal, Oscar; Barrero, Carlos A.; Merali, Salim

    2013-01-01

    Highlights: •Identification of a novel Nrf2 translational repression mechanism. •The repressor is within the 3′ portion of the Nrf2 ORF. •The translation of Nrf2 or eGFP is reduced by the regulatory element. •The translational repression can be reversed with synonymous codon substitutions. •The molecular mechanism requires the mRNA sequence, but not the encoded amino acids. -- Abstract: Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a transcription factor that is essential for the regulation of an effective antioxidant and detoxifying response. The regulation of its activity can occur at transcription, translation and post-translational levels. Evidence suggests that under environmental stress conditions, new synthesis of Nrf2 is required – a process that is regulated by translational control and is not fully understood. Here we described the identification of a novel molecular process that under basal conditions strongly represses the translation of Nrf2 within the open reading frame (ORF). This mechanism is dependent on the mRNA sequence within the 3′ portion of the ORF of Nrf2 but not in the encoded amino acid sequence. The Nrf2 translational repression can be reversed with the use of synonymous codon substitutions. This discovery suggests an additional layer of control to explain the reason for the low Nrf2 concentration under quiescent state

  9. NRF2 Protection against Liver Injury Produced by Various Hepatotoxicants

    Directory of Open Access Journals (Sweden)

    Jie Liu

    2013-01-01

    Full Text Available To investigate the role of Nrf2 as a master defense against the hepatotoxicity produced by various chemicals, Nrf2-null, wild-type, Keap1-knock down (Keap1-Kd and Keap1-hepatocyte knockout (Keap1-HKO mice were used as a “graded Nrf2 activation” model. Mice were treated with 14 hepatotoxicants at appropriate doses, and blood and liver samples were collected thereafter (6 h to 7 days depending on the hepatotoxicant. Graded activation of Nrf2 offered a Nrf2-dependent protection against the hepatotoxicity produced by carbon tetrachloride, acetaminophen, microcystin, phalloidin, furosemide, cadmium, and lithocholic acid, as evidenced by serum alanine aminotransferase (ALT activities and by histopathology. Nrf2 activation also offered moderate protection against liver injury produced by ethanol, arsenic, bromobenzene, and allyl alcohol but had no effects on the hepatotoxicity produced by D-galactosamine/endotoxin and the Fas ligand antibody Jo-2. Graded Nrf2 activation reduced the expression of inflammatory genes (MIP-2, mKC, IL-1β, IL-6, and TNFα, oxidative stress genes (Ho-1, Egr1, ER stress genes (Gadd45 and Gadd153, and genes encoding cell death (Noxa, Bax, Bad, and caspase3. Thus, this study demonstrates that Nrf2 prevents the liver from many, but not all, hepatotoxicants. The Nrf2-mediated protection is accompanied by induction of antioxidant genes, suppression of inflammatory responses, and attenuation of oxidative stress.

  10. Oral and Maxillofacial Surgery Foundation Research and Fellowship Awards: A 26-Year Review at Massachusetts General Hospital and Harvard School of Dental Medicine.

    Science.gov (United States)

    Inverso, Gino; Chuang, Sung-Kiang; Kaban, Leonard B

    2016-02-01

    The purpose of this study was to review outcomes of the Oral and Maxillofacial Surgery (OMS) Foundation's funding awards to members of the OMS department at Massachusetts General Hospital (MGH) in terms of projects completed, abstracts presented, peer-reviewed publications, and career trajectories of recipients. Data were collected from MGH and OMS Foundation records and interviews with award recipients. Primary outcome variables included 1) number of awards and award types, 2) funding amount, 3) project completion, 4) number of presented abstracts, 5) conversion from abstracts to publications, 6) number of peer-reviewed publications, 7) career trajectories of awardees, and 8) additional extramural funding. Eleven Student Research Training Awards provided $135,000 for 39 projects conducted by 37 students. Of these, 34 (87.2%) were completed. There were 30 student abstracts presented, 21 peer-reviewed publications, and a publication conversion rate of 58.8%. Faculty research awards comprised $1,510,970 for 22 research projects by 12 faculty members and two research fellows. Of the 22 funded projects, 21 (95.5%) were completed. There were 110 faculty and research fellow abstracts presented and 113 peer-reviewed publications, for a publication conversion rate of 93.8%. In the student group, 17 of 37 (45.9%) are enrolled in or are applying for OMS residencies. Of the 10 students who have completed OMS training, 3 (30%) are in full-time academic positions. Of the 12 faculty recipients, 9 (75%) remain in OMS academic practice. During this time period, the department received $9.9 million of extramural foundation or National Institutes of Health funding directly or indirectly related to the OMS Foundation grants. The results of this study indicate that 90.2% of projects funded by the OMS Foundation have been completed. Most projects resulted in abstracts and publications in peer-reviewed journals. These grants encouraged students to pursue OMS careers and aided OMS

  11. Nrf2 transcription factor gene regulates basal transcription of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-19

    Oct 19, 2009 ... induction in the Nrf2(-/-) mouse brain. In contrast, there ... mouse brain by any of the chemicals used . Key words: .... The blots were then probed with the human SOD2 .... Nrf2, null and wild mice as part of my PhD work. I wish.

  12. A randomized controlled trial of skin care protocols for facial resurfacing: lessons learned from the Plastic Surgery Educational Foundation's Skin Products Assessment Research study.

    Science.gov (United States)

    Pannucci, Christopher J; Reavey, Patrick L; Kaweski, Susan; Hamill, Jennifer B; Hume, Keith M; Wilkins, Edwin G; Pusic, Andrea L

    2011-03-01

    The Skin Products Assessment Research Committee was created by the Plastic Surgery Educational Foundation in 2006. The Skin Products Assessment Research study aims were to (1) develop an infrastructure for Plastic Surgery Educational Foundation-conducted, industry-sponsored research in facial aesthetic surgery and (2) test the research process by comparing outcomes of the Obagi Nu-Derm System versus conventional therapy as treatment adjuncts for facial resurfacing procedures. The Skin Products Assessment Research study was designed as a multicenter, double-blind, randomized, controlled trial. The study was conducted in women with Fitzpatrick type I to IV skin, moderate to severe facial photodamage, and periocular and/or perioral fine wrinkles. Patients underwent chemical peel or laser facial resurfacing and were randomized to the Obagi Nu-Derm System or a standard care regimen. The study endpoints were time to reepithelialization, erythema, and pigmentation changes. Fifty-six women were enrolled and 82 percent were followed beyond reepithelialization. There were no significant differences in mean time to reepithelialization between Obagi Nu-Derm System and control groups. The Obagi Nu-Derm System group had a significantly higher median erythema score on the day of surgery (after 4 weeks of product use) that did not persist after surgery. Test-retest photographic evaluations demonstrated that both interrater and intrarater reliability were adequate for primary study outcomes. The authors demonstrated no significant difference in time to reepithelialization between patients who used the Obagi Nu-Derm System or a standard care regimen as an adjunct to facial resurfacing procedures. The Skin Products Assessment Research team has also provided a discussion of future challenges for Plastic Surgery Educational Foundation-sponsored clinical research for readers of this article.

  13. The role of foundations: Rockefeller Foundation.

    Science.gov (United States)

    Rockefeller, David

    The consequences of climate change and the impacts of human activity on the environment have made it clearer than ever before that we must evolve our current model of public health to better account for the inextricable link between human health and the natural systems on which it depends-creating a "public health 2.0" that builds on the innovations of the twentieth century to account for a world where humans have bypassed planetary boundaries to achieve well-being. First coined at the Rockefeller Foundation's Centennial gathering in Beijing in 2013, "Planetary Health" will factor in future health and environmental harms over present-day gains, particularly those that disproportionately affect the poor and those in developing nations. To build this new field, foundations must address the challenge of information, increasing support for research to bridge knowledge gaps on the links between economic development, natural systems, and human health.

  14. Establishment of the foundation for international collaborating research with US NASA FTCSC to develop space, military and special purpose food

    International Nuclear Information System (INIS)

    Jo, Chul Hun; Byun, Myung Woo; Lee, Ju Wun; Kim, Dong Ho; Kim, Kyung Pho; Kim, Jang Ho; Kwon, Jung Ho

    2005-08-01

    In the space era of 21st century, the advancement of aerospace field is essential for ensuring the national security and raising the national status. Internationally spacefood and space life support system is considered as an limitedly developed technology area. Establishment of the foundation for collaborating study with NASA FTCSC to develop space, military, and special food. Acquirement of the basis of the technology development for safe, long-term preservation of military and special purpose food to ensure national security as well as health and welfare

  15. The origins of the research on the foundations of quantum mechanics (and other critical activities) in Italy during the 1970s

    Science.gov (United States)

    Baracca, Angelo; Bergia, Silvio; Del Santo, Flavio

    2017-02-01

    We present a reconstruction of the studies on the Foundations of Quantum Mechanics carried out in Italy at the turn of the 1960s. Actually, they preceded the revival of the interest of the American physicists towards the foundations of quantum mechanics around mid-1970s, recently reconstructed by David Kaiser in a book of 2011. An element common to both cases is the role played by the young generation, even though the respective motivations were quite different. In the US they reacted to research cuts after the war in Vietnam, and were inspired by the New Age mood. In Italy the dissatisfaction of the young generations was rooted in the student protests of 1968 and the subsequent labour and social fights, which challenged the role of scientists. The young generations of physicists searched for new scientific approaches and challenged their own scientific knowledge and role. The criticism to the foundations of quantum mechanics and the perspectives of submitting them to experimental tests were perceived as an innovative research field and this attitude was directly linked to the search for an innovative and radical approach in the history of science. All these initiatives gave rise to booming activity throughout the 1970s, contributing to influence the scientific attitude and the teaching approach.

  16. Pyrrolidine dithiocarbamate activates the Nrf2 pathway in astrocytes.

    Science.gov (United States)

    Liddell, Jeffrey R; Lehtonen, Sarka; Duncan, Clare; Keksa-Goldsteine, Velta; Levonen, Anna-Liisa; Goldsteins, Gundars; Malm, Tarja; White, Anthony R; Koistinaho, Jari; Kanninen, Katja M

    2016-02-26

    Endogenous defense against oxidative stress is controlled by nuclear factor erythroid 2-related factor 2 (Nrf2). The normal compensatory mechanisms to combat oxidative stress appear to be insufficient to protect against the prolonged exposure to reactive oxygen species during disease. Counterbalancing the effects of oxidative stress by up-regulation of Nrf2 signaling has been shown to be effective in various disease models where oxidative stress is implicated, including Alzheimer's disease. Stimulation of Nrf2 signaling by small-molecule activators is an appealing strategy to up-regulate the endogenous defense mechanisms of cells. Here, we investigate Nrf2 induction by the metal chelator and known nuclear factor-κB inhibitor pyrrolidine dithiocarbamate (PDTC) in cultured astrocytes and neurons, and mouse brain. Nrf2 induction is further examined in cultures co-treated with PDTC and kinase inhibitors or amyloid-beta, and in Nrf2-deficient cultures. We show that PDTC is a potent inducer of Nrf2 signaling specifically in astrocytes and demonstrate the critical role of Nrf2 in PDTC-mediated protection against oxidative stress. This induction appears to be regulated by both Keap1 and glycogen synthase kinase 3β. Furthermore, the presence of amyloid-beta magnifies PDTC-mediated induction of endogenous protective mechanisms, therefore suggesting that PDTC may be an effective Nrf2 inducer in the context of Alzheimer's disease. Finally, we show that PDTC increases brain copper content and glial expression of heme oxygenase-1, and decreases lipid peroxidation in vivo, promoting a more antioxidative environment. PDTC activates Nrf2 and its antioxidative targets in astrocytes but not neurons. These effects may contribute to the neuroprotection observed for PDTC in models of Alzheimer's disease.

  17. Characterization of bridge foundations workshop report.

    Science.gov (United States)

    2013-11-01

    "In 2013, the Federal Highway Administration proposed a new research program for the characterization of bridge foundations. To narrow the focus and develop a research roadmap for the program, a workshop on Characterization of Bridge Foundations...

  18. Foundations of mechanics

    International Nuclear Information System (INIS)

    Zorski, Henryk; Bazanski, Stanislaw; Gutowski, Roman; Slawianowski, Jan; Wilmanski, Krysztof; Wozniak, Czeslaw

    1992-01-01

    In the last 3 decades the field of mechanics has seen spectacular progress due to the demand for applications in problems of cosmology, thermonuclear fusion, metallurgy, etc. This book provides a broad and thorough overview on the foundations of mechanics. It discusses theoretical mechanics and continuum mechanics, as well as phenomenological thermodynamics, quantum mechanics and relativistic mechanics. Each chapter presents the basic physical facts of interest without going into details and derivations and without using advanced mathematical formalism. The first part constitutes a classical exposition of Lagrange's and Hamiltonian's analytical mechanics on which most of the continuum theory is based. The section on continuum mechanics focuses mainly on the axiomatic foundations, with many pointers for further research in this area. Special attention is given to modern continuum thermodynamics, both for the foundations and applications. A section on quantum mechanics is also included, since the phenomenological description of various quantum phenomena is becoming of increasing importance. refs.; figs.; tabs

  19. Activation of Nrf2 protects against triptolide-induced hepatotoxicity.

    Directory of Open Access Journals (Sweden)

    Jia Li

    Full Text Available Triptolide, the major active component of Tripterygium wilfordii Hook f. (TWHF, has a wide range of pharmacological activities. However, the toxicities of triptolide, particularly the hepatotoxicity, limit its clinical application. The hepatotoxicity of triptolide has not been well characterized yet. The aim of this study was to investigate the role of NF-E2-related factor 2 (Nrf2 in triptolide-induced toxicity and whether activation of Nrf2 could protect against triptolide-induced hepatotoxicity. The results showed that triptolide caused oxidative stress and cell damage in HepG2 cells, and these toxic effects could be aggravated by Nrf2 knockdown or be counteracted by overexpression of Nrf2. Treatment with a typical Nrf2 agonist, sulforaphane (SFN, attenuated triptolide-induced liver dysfunction, structural damage, glutathione depletion and decrease in antioxidant enzymes in BALB/C mice. Moreover, the hepatoprotective effect of SFN on triptolide-induced liver injury was associated with the activation of Nrf2 and its downstream targets. Collectively, these results indicate that Nrf2 activation protects against triptolide-induced hepatotoxicity.

  20. Nrf2, the Master Regulator of Anti-Oxidative Responses

    Directory of Open Access Journals (Sweden)

    Sandra Vomund

    2017-12-01

    Full Text Available Tight regulation of inflammation is very important to guarantee a balanced immune response without developing chronic inflammation. One of the major mediators of the resolution of inflammation is the transcription factor: the nuclear factor erythroid 2-like 2 (Nrf2. Stabilized following oxidative stress, Nrf2 induces the expression of antioxidants as well as cytoprotective genes, which provoke an anti-inflammatory expression profile, and is crucial for the initiation of healing. In view of this fundamental modulatory role, it is clear that both hyper- or hypoactivation of Nrf2 contribute to the onset of chronic diseases. Understanding the tight regulation of Nrf2 expression/activation and its interaction with signaling pathways, known to affect inflammatory processes, will facilitate development of therapeutic approaches to prevent Nrf2 dysregulation and ameliorate chronic inflammatory diseases. We discuss in this review the principle mechanisms of Nrf2 regulation with a focus on inflammation and autophagy, extending the role of dysregulated Nrf2 to chronic diseases and tumor development.

  1. Bucket Foundation Response Under Various Displacement Rates

    DEFF Research Database (Denmark)

    Vaitkunaite, Evelina; Nielsen, Benjaminn Nordahl; Ibsen, Lars Bo

    2016-01-01

    in a multi-bucket foundation system. The foundation model is at a scale of approximately 1:20 prototype foundation size. The tests are performed in a pressure tank with the foundation model installed in dense sand. Based on the data, the conclusion is that the bucket foundation design in a storm case should......The present testing program aims at showing the pore pressure response around a bucket foundation skirt as well as the load and displacement change due to ten different displacement rates. Research findings are useful for a numerical model calibration focusing on the design of the upwind foundation...

  2. The PTEN/NRF2 Axis Promotes Human Carcinogenesis

    DEFF Research Database (Denmark)

    Rojo, Ana I; Rada, Patricia; Mendiola, Marta

    2014-01-01

    and tumorigenic advantage. Tissue microarrays from endometrioid carcinomas showed that 80% of PTEN-negative tumors expressed high levels of NRF2 or its target heme oxygenase-1 (HO-1). INNOVATION: These results uncover a new mechanism of oncogenic activation of NRF2 by loss of its negative regulation by PTEN/GSK-3....../β-TrCP that may be relevant to a large number of tumors, including endometrioid carcinomas. CONCLUSION: Increased activity of NRF2 due to loss of PTEN is instrumental in human carcinogenesis and represents a novel therapeutic target. Antioxid. Redox Signal. 21, 2498-2514....

  3. The grave is wide: the Hibakusha of Hiroshima and Nagasaki and the legacy of the Atomic Bomb Casualty Commission and the Radiation Effects Research Foundation.

    Science.gov (United States)

    O'Malley, Gerald F

    2016-07-01

    Following the atomic bomb attacks on Japan in 1945, scientists from the United States and Japan joined together to study the Hibakusha - the bomb affected people in what was advertised as a bipartisan and cooperative effort. In reality, despite the best efforts of some very dedicated and earnest scientists, the early years of the collaboration were characterized by political friction, censorship, controversy, tension, hostility, and racism. The 70-year history, scientific output and cultural impact of the Atomic Bomb Casualty Commission and the Radiation Effects Research Foundation are described in the context of the development of Occupied Japan.

  4. Glaucoma Foundation

    Science.gov (United States)

    ... Options: SIZE CONTRAST Search Home About TGF About Glaucoma About Exfoliation Syndrome Research Center Contact Us Get ... tear glands, and a common preservative in many glaucoma medications can worsen the symptoms. The main treatment ...

  5. The Nrf1 and Nrf2 Balance in Oxidative Stress Regulation and Androgen Signaling in Prostate Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Michelle A. [Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States); Abdel-Mageed, Asim B. [Department of Urology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States); Mondal, Debasis, E-mail: dmondal@tulane.edu [Department of Pharmacology, Tulane University Medical Center, 1430 Tulane Avenue, New Orleans, LA 70112 (United States)

    2010-06-21

    Reactive oxygen species (ROS) signaling has recently sparked a surge of interest as being the molecular underpinning for cancer cell survival, but the precise mechanisms involved have not been completely elucidated. This review covers the possible roles of two ROS-induced transcription factors, Nrf1 and Nrf2, and the antioxidant proteins peroxiredoxin-1 (Prx-1) and Thioredoxin-1 (Txn-1) in modulating AR expression and signaling in aggressive prostate cancer (PCa) cells. In androgen independent (AI) C4-2B cells, in comparison to the parental androgen dependent (AD) LNCaP cells, we present evidence of high Nrf1 and Prx-1 expression and low Nrf2 expression in these aggressive PCa cells. Furthermore, in DHT treated C4-2B cells, increased expression of the p65 (active) isoform of Nrf1 correlated with enhanced AR transactivation. Our findings implicate a crucial balance of Nrf1 and Nrf2 signaling in regulating AR activity in AI-PCa cells. Here we will discuss how understanding the mechanisms by which oxidative stress may affect AR signaling may aid in developing novel therapies for AI-PCa.

  6. [Analysis of hot spots and trend of molecular pharmacognosy research based on project supported by National Natural Science Foundation of 1995-2014].

    Science.gov (United States)

    Wang, Jun-Wen; Liu, Yang; Tong, Yuan-Yuan; Yang, Ce; Li, Hai-Yan

    2016-05-01

    This study collected 1995-2014 molecular pharmacognosy study, a total of 595 items, funded by Natural Science Foundation of China (NSFC). TDA and Excel software were used to analyze the data of the projects about general situation, hot spots of research with rank analytic and correlation analytic methods. Supported by NSFC molecular pharmacognosy projects and funding a gradual increase in the number of, the proportion of funds for pharmaceutical research funding tends to be stable; mainly supported by molecular biology methods of genuine medicinal materials, secondary metabolism and Germplasm Resources Research; hot drugs including Radix Salviae Miltiorrhizae, Radix Rehmanniae, Cordyceps sinensis, hot contents including tanshinone biosynthesis, Rehmannia glutinosa continuous cropping obstacle. Copyright© by the Chinese Pharmaceutical Association.

  7. Nrf2 and Redox Status in Prediabetic and Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Angélica S. Jiménez-Osorio

    2014-11-01

    Full Text Available The redox status associated with nuclear factor erythroid 2-related factor-2 (Nrf2 was evaluated in prediabetic and diabetic subjects. Total antioxidant status (TAS in plasma and erythrocytes, glutathione (GSH and malondialdehyde (MDA content and activity of antioxidant enzymes were measured as redox status markers in 259 controls, 111 prediabetics and 186 diabetic type 2 subjects. Nrf2 was measured in nuclear extract fractions from peripheral blood mononuclear cells (PBMC. Nrf2 levels were lower in prediabetic and diabetic patients. TAS, GSH and activity of glutamate cysteine ligase were lower in diabetic subjects. An increase of MDA and superoxide dismutase activity was found in diabetic subjects. These results suggest that low levels of Nrf2 are involved in the development of oxidative stress and redox status disbalance in diabetic patients.

  8. Cooperation Agreement between the European Organization for Nuclear Research (CERN) and The Qatar Foundation for Education, Science and Community Development concerning Scientific and Technical Co-operation in High Energy Physics

    CERN Document Server

    2016-01-01

    Cooperation Agreement between the European Organization for Nuclear Research (CERN) and The Qatar Foundation for Education, Science and Community Development concerning Scientific and Technical Co-operation in High Energy Physics

  9. Mathematical foundations of thermodynamics

    CERN Document Server

    Giles, R; Stark, M; Ulam, S

    2013-01-01

    Mathematical Foundations of Thermodynamics details the core concepts of the mathematical principles employed in thermodynamics. The book discusses the topics in a way that physical meanings are assigned to the theoretical terms. The coverage of the text includes the mechanical systems and adiabatic processes; topological considerations; and equilibrium states and potentials. The book also covers Galilean thermodynamics; symmetry in thermodynamics; and special relativistic thermodynamics. The book will be of great interest to practitioners and researchers of disciplines that deal with thermodyn

  10. Targeted deletion of Nrf2 reduces urethane-induced lung tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Alison K Bauer

    Full Text Available Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2(+/+ and Nrf2(-/- mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2(-/- mice compared to Nrf2(+/+ mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2(-/- mice than in Nrf2(+/+ mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2(+/+ mice relative to Nrf2(-/- mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy.

  11. [Overview of research projects funding in traditional Chinese medicine oncology field supported by National Natural Science Foundation of China].

    Science.gov (United States)

    Tang, Dong-Xin; Chen, Lian-Yu; Guo, Shu-Zhen; Han, Li-Wei; Zhang, Feng-Zhu

    2017-05-01

    In this paper, the funding situation of traditional Chinese medicine oncology research projects supported by National Natural Science Fund from 1986-2016 was reviewed. The characteristics of funded projects were summarized from funding amount, funding expenses, funding category, and the main research contents of projects, etc. At the same time, the main problems in the projects were analyzed in this paper, in order to provide reference for the relevant fund applicants. Copyright© by the Chinese Pharmaceutical Association.

  12. Studies on the health effects of a-bomb radiation exposure appeared in health examinations of adult survivors by the Radiation Effects Research Foundation

    International Nuclear Information System (INIS)

    Yamada, Michiko

    2006-01-01

    The Research Foundation has conducted the health examinations in the title since 1958, based on which studies of a cohort type have been performed, and their results at present are summarized in this paper. Subjects have included a cohort of about 120000 cases in total. They have been those 4993 initial cases (the center group) exposed to estimated radiation doses of 4 -6 Gy within the distance of 2 km from the hypocenter and with acute exposure symptoms either in Hiroshima or Nagasaki, and 19961 cases (exposed ones within 2 km from the hypocenter but without the symptoms, exposed residents in the city 3 km far from the hypocenter, or ones absent in the city at explosion) matched to the above center group in the city, age and sex. Lower statures and weights are noted in some of the center group who were in growing ages at exposure. Increases of prevalence or incidence rate are suggested in malignant tumors, diseases of the thyroid and parathyroid, uterine myoma, chronic liver diseases, cataract, circulatory diseases, abnormal hemoglobin value, and psychological states. Relative risk at 1 Gy for incidence of non-cancer diseases is calculated and presented. Results are not always consistent with those of such population exposed to <6 Gy as that of Chernobyl Accident, of radiation technologist and of people accidentally exposed to environmental radiation. The Foundation is to continue the study and more profound results of radiation effects are expected to be obtainable. (T.I)

  13. Research on the Horizontal Displacement Coefficient of Soil Surrounding Pile in Layered Foundations by Considering the Soil Mass’s Longitudinal Continuity

    Directory of Open Access Journals (Sweden)

    Yao Wen-Juan

    2013-01-01

    Full Text Available When utilizing the p-y curve to simulate the nonlinear characteristics of soil surrounding pile in layered foundations, due to having not taken into account the soil mass’s longitudinal continuity, the calculation deviation of horizontal displacement increases with the growth of a load. This paper adopted the layered elasticity system theory to consider the soil mass’s longitudinal continuity, as well as utilizing the research method for layered isotropic bodies, assuming that the horizontal resistance is evenly distributed around the perimeter of the pile's cross-section. Then an appropriate transfer matrix method of horizontal displacement coefficient for the soil surrounding pile in layered foundations was established. According to the calculation principle of finite element equivalent load, the horizontal displacement coefficient matrix was deduced as well as providing a corrected formula for the horizontal displacement of soil surrounding pile through the p-y curve method when the external load was increased. Following the established model, a program was created which was used for calculating and analyzing the horizontal displacement coefficient matrix of three-layered soil in order to verify this method’s validity and rationale. Where there is a relatively large discrepancy in the soil layers’ properties, this paper’s method is able to reflect the influence on the layered soil’s actual distributional difference as well as the nearby soil layers’ interaction.

  14. ["Maintaining a Common Culture"--the German Research Foundation and the Austrian-German scientific aid in the interbellum].

    Science.gov (United States)

    Fengler, Silke; Luxbacher, Günther

    2011-12-01

    After the end of the Great War, private as well as public research funding in Austria was anaemic and slow to develop. Whereas the German state-funded Deutsche Forschungsgemeinschaft (DFG) was established as early as 1920, first steps in that direction were only taken in Austria in the late 1920s. In 1929, the Osterreichisch-deutsche Wissenschaftshilfe (ODW) was founded under the auspices of the Austrian Academy of Sciences and the DFG. Although prima facie on an equal footing, the new research funding organisation was in fact highly dependent on its German cooperation partner. The article explores for the first time ODW's position within the German and Austrian science and foreign policies, which aimed to promote the idea of unification of both states within the German Reich. A quantitative analysis of the subsidies policy in the first five years of existence shows that the ODW gave financial aid primarily to conservative research fields, affecting the intellectual balance of power in the First Austrian Republic. Policy continuities and discontinuities of the organisation in the course of the national-socialist rise to power in Germany after 1933 are examined in the second part of the article. The article thus both increases our knowledge about the most important German research funding organisation DFG, and identifies some of the fundamental structural features of Austrian science policy in the interwar years.

  15. Netherlands foundation for radioastronomy

    International Nuclear Information System (INIS)

    1979-01-01

    A report of the board is followed by departmental reports from the Westerbork Telescope Group, Dwingeloo Telescope Group, Computer Group, Laboratory and Central Technical Services, Astronomy Group, Administration of the Foundation/General Affairs and Personnel Council. Astronomical reports describe radio astronomical research carried out by the Foundation staff and at the Kapteyn Laboratory Groningen, Leiden Observatory, Utrecht Observatory and the Laboratorio di Radioastronomia Bologna, Italy. Progress in the extension of the synthesis radio telescope and investigations into the possibility of substantially increasing the SRT data rate for solar observations, are outlined. Appendices shows the organisational structure, the names of the employees, the operating budget, the observing facilities at Westerbork and Dwingeloo, and the publications and reports published in 1978 and related to observations made with these facilities. (C.F.)

  16. Web services foundations

    CERN Document Server

    Bouguettaya, Athman; Daniel, Florian

    2013-01-01

    Web services and Service-Oriented Computing (SOC) have become thriving areas of academic research, joint university/industry research projects, and novel IT products on the market. SOC is the computing paradigm that uses Web services as building blocks for the engineering of composite, distributed applications out of the reusable application logic encapsulated by Web services. Web services could be considered the best-known and most standardized technology in use today for distributed computing over the Internet.Web Services Foundations is the first installment of a two-book collection coverin

  17. Nrf2 regulates cellular behaviors and Notch signaling in oral squamous cell carcinoma cells.

    Science.gov (United States)

    Fan, Hong; Paiboonrungruan, Chorlada; Zhang, Xinyan; Prigge, Justin R; Schmidt, Edward E; Sun, Zheng; Chen, Xiaoxin

    2017-11-04

    Oxidative stress is known to play a pivotal role in the development of oral squamous cell carcinoma (OSCC). We have demonstrated that activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has chemopreventive effects against oxidative stress-associated OSCC. However, Nrf2 have dual roles in cancer development; while it prevents carcinogenesis of normal cells, hyperactive Nrf2 also promotes the survival of cancer cells. This study is aimed to understand the function of Nrf2 in regulating cellular behaviors of OSCC cells, and the potential mechanisms through which Nrf2 facilitates OSCC. We established the Nrf2-overexpressing and Nrf2-knockdown OSCC cell lines, and examined the function of Nrf2 in regulating cell proliferation, migration, invasion, cell cycle and colony formation. Our data showed that Nrf2 overexpression promoted cancer phenotypes in OSCC cells, whereas Nrf2 silencing inhibited these phenotypes. In addition, Nrf2 positively regulated Notch signaling pathway in OSCC cells in vitro. Consistent with this observation, Nrf2 activation in Keap1 -/- mice resulted in not only hyperproliferation of squamous epithelial cells in mouse tongue as evidenced by increased expression of PCNA, but also activation of Notch signaling in these cells as evidenced by increased expression of NICD1 and Hes1. In conclusion, Nrf2 regulates cancer behaviors and Notch signaling in OSCC cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. A strategy for the generation, characterization and distribution of animal models by The Michael J. Fox Foundation for Parkinson’s Research

    Directory of Open Access Journals (Sweden)

    Marco A. S. Baptista

    2013-11-01

    Full Text Available Progress in Parkinson’s disease (PD research and therapeutic development is hindered by many challenges, including a need for robust preclinical animal models. Limited availability of these tools is due to technical hurdles, patent issues, licensing restrictions and the high costs associated with generating and distributing these animal models. Furthermore, the lack of standardization of phenotypic characterization and use of varying methodologies has made it difficult to compare outcome measures across laboratories. In response, The Michael J. Fox Foundation for Parkinson’s Research (MJFF is directly sponsoring the generation, characterization and distribution of preclinical rodent models, enabling increased access to these crucial tools in order to accelerate PD research. To date, MJFF has initiated and funded the generation of 30 different models, which include transgenic or knockout models of PD-relevant genes such as Park1 (also known as Park4 and SNCA, Park8 (LRRK2, Park7 (DJ-1, Park6 (PINK1, Park2 (Parkin, VPS35, EiF4G1 and GBA. The phenotypic characterization of these animals is performed in a uniform and streamlined manner at independent contract research organizations. Finally, MJFF created a central repository at The Jackson Laboratory (JAX that houses both non-MJFF and MJFF-generated preclinical animal models. Funding from MJFF, which subsidizes the costs involved in transfer, rederivation and colony expansion, has directly resulted in over 2500 rodents being distributed to the PD community for research use.

  19. The C-terminal domain of Nrf1 negatively regulates the full-length CNC-bZIP factor and its shorter isoform LCR-F1/Nrf1β; both are also inhibited by the small dominant-negative Nrf1γ/δ isoforms that down-regulate ARE-battery gene expression.

    Science.gov (United States)

    Zhang, Yiguo; Qiu, Lu; Li, Shaojun; Xiang, Yuancai; Chen, Jiayu; Ren, Yonggang

    2014-01-01

    The C-terminal domain (CTD, aa 686-741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

  20. Corporate Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Thomsen, Steen

    1999-01-01

    Industrial foundations are self-governing non profit institutions that own business companies. This ownership structure is found in a fair number of Northern European companies, some of them successful world class competitors. Standard agency theory would predict foundation-owned companies...... to be relatively inefficient since they lack monitoring by residual claimants and access to equity finance from the stock market. Nevertheless, empirical research (Thomsen 1996) has found that Danish foundation-owned companies do no worse in terms of profitability and growth than companies with dispersed ownership...

  1. The status of the seventh report in the series Biological Effects of Ionizing Radiations and a revised dosimetry for the Radiation Effects Research Foundation's A-bomb studies

    International Nuclear Information System (INIS)

    Douple, Evan; Jostes, Rick

    2002-01-01

    Results of a National Academies workshop and feasibility study led US Governmental agencies to request the Board on Radiation Effects Research of the National Research Council to commence a risk assessment study in 1998 as the seventh report in the series Biological Effects of Ionizing Radiations (BEIR VII). Originally targeted for completion in the autumn of 2001, the study Potential Health Effects of Exposure to Low Dose, Low-LET Ionizing Radiation was extended until the autumn of 2003 at the request of the sponsors. Two factors contributing to this decision are discussed: a revised dosimetry to update DS86 for the Radiation Effects Research Foundation's A-bomb-survivor studies and the potential for new information to become available from low-dose studies that are under way. Epidemiological and biological data since BEIR V are being considered by a BEIR VII committee composed of 17 members. The committee's statement of task is reviewed along with the major recommendations of the recent National Research Council report on the status of DS86 - recommendations that are being implemented by US and Japan dosimetry working groups. (author)

  2. Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus

    Science.gov (United States)

    Suzuki, Takafumi; Seki, Shiori; Hiramoto, Keiichiro; Naganuma, Eriko; Kobayashi, Eri H.; Yamaoka, Ayaka; Baird, Liam; Takahashi, Nobuyuki; Sato, Hiroshi; Yamamoto, Masayuki

    2017-01-01

    NF-E2-related factor-2 (Nrf2) regulates cellular responses to oxidative and electrophilic stress. Loss of Keap1 increases Nrf2 protein levels, and Keap1-null mice die of oesophageal hyperkeratosis because of Nrf2 hyperactivation. Here we show that deletion of oesophageal Nrf2 in Keap1-null mice allows survival until adulthood, but the animals develop polyuria with low osmolality and bilateral hydronephrosis. This phenotype is caused by defects in water reabsorption that are the result of reduced aquaporin 2 levels in the kidney. Renal tubular deletion of Keap1 promotes nephrogenic diabetes insipidus features, confirming that Nrf2 activation in developing tubular cells causes a water reabsorption defect. These findings suggest that Nrf2 activity should be tightly controlled during development in order to maintain renal homeostasis. In addition, tissue-specific ablation of Nrf2 in Keap1-null mice might create useful animal models to uncover novel physiological functions of Nrf2. PMID:28233855

  3. Charity Starts … at Work? Conceptual Foundations for Research with Businesses that Donate to Food Redistribution Organisations

    Directory of Open Access Journals (Sweden)

    Elisha Vlaholias

    2015-06-01

    Full Text Available As global concern about sustainability, food waste, and poverty increases, there is an urgent need to understand what motivates businesses to adopt pro-social and pro-environmental behaviours. This paper suggests that food redistribution organisations hold both pro-social and pro-environmental aims, due to their concern with reducing food surplus and food insecurity. To achieve this, they must motivate food businesses to donate their surplus food. However, little is known about the values, attitudes, and motives of food industry donors. The purpose of this paper is to provide a theoretical and conceptual overview to set out principles from which empirical data on food redistribution will be analysed or critiqued. Specifically, it explores pro-social and pro-environmental literature, as these fields have examined the motivations behind donations and reducing environmental impact. This review highlights that charitable giving of food is different to other inorganic material, such as money. Thus, future research is needed to capture the unique temporal, emotional, social, and environmental factors that motivate food donations. This information may contribute to the development of strategies that target and motivate people from the food industry to become food donors. Alternatively, it may reveal concerns about food donations, and highlight the need for other approaches to food waste and food insecurity.

  4. Foundations of genetic algorithms 1991

    CERN Document Server

    1991-01-01

    Foundations of Genetic Algorithms 1991 (FOGA 1) discusses the theoretical foundations of genetic algorithms (GA) and classifier systems.This book compiles research papers on selection and convergence, coding and representation, problem hardness, deception, classifier system design, variation and recombination, parallelization, and population divergence. Other topics include the non-uniform Walsh-schema transform; spurious correlations and premature convergence in genetic algorithms; and variable default hierarchy separation in a classifier system. The grammar-based genetic algorithm; condition

  5. Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission

    Directory of Open Access Journals (Sweden)

    Gary B. O'Mealey

    2017-04-01

    Full Text Available The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond to oxidative and xenobiotic stresses. Sulforaphane (SFN, an electrophilic isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE pathway and has become a molecule-of-interest in the treatment of diseases in which chronic oxidative stress plays a major etiological role. We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1 cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN mitigates the recruitment and/or retention of the soluble fission factor Drp1 to mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These data demonstrate that the beneficial properties of SFN extend beyond activation of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current use of this agent in multiple clinical trials.

  6. Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2.

    Directory of Open Access Journals (Sweden)

    Vera Cavalcanti Araújo

    Full Text Available Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM, as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

  7. PREFACE: International Scientific and Research Conference on Topical Issues in Aeronautics and Astronautics (dedicated to the 55th anniversary from the foundation of SibSAU)

    Science.gov (United States)

    2015-10-01

    The International Scientific and Research Conference ''Topical Issues in Aeronautics and Astronautics'' is one of the most significant scientific conferences arranged by the Reshetnev Siberian State Aerospace University (SibSAU) which is located in the Krasnoyarsk Region of Russian Federation. In April 2015 this Conference was dedicated to the 55th anniversary from the foundation of the University. Traditionally, the Conference is seen as emblematic of the University's specialty and is annually organized in April, when the first human travelled into space. This Conference is arranged for undergraduate, graduate and postgraduate students, scientists and lecturers, as well as developers, designers and constructors representing leading companies and enterprises of the aerospace sector to give opportunities to present their projects, research work and results. The Conference is a great chance to connect scientists and highly-qualified and skilled specialists with a new community of future scientists and practitioners in the aerospace sector. The Conference proceedings include papers presented by creative young specialists closely connected with aviation and space vehicles - design, production, problem-solving in space machine building and aerospace education, macro- and microeconomic development of the field, new approaches to solving philosophical and social problems, - experienced scientists and specialists, and all those who want to dedicate themselves to aeronautics and astronautics. The selected papers are presented in these proceedings to share University research results, innovations and cutting-edge technologies with the international community to develop aeronautics and astronautics on a global scale.

  8. Promoting physical therapists’ of research evidence to inform clinical practice: part 1 - theoretical foundation, evidence, and description of the PEAK program

    Science.gov (United States)

    2014-01-01

    Background There is a need for theoretically grounded and evidence-based interventions that enhance the use of research evidence in physical therapist practice. This paper and its companion paper introduce the Physical therapist-driven Education for Actionable Knowledge translation (PEAK) program, an educational program designed to promote physical therapists’ integration of research evidence into clinical decision-making. The pedagogical foundations for the PEAK educational program include Albert Bandura’s social cognitive theory and Malcolm Knowles’s adult learning theory. Additionally, two complementary frameworks of knowledge translation, the Promoting Action on Research Implementation in Health Services (PARiHS) and Knowledge to Action (KTA) Cycle, were used to inform the organizational elements of the program. Finally, the program design was influenced by evidence from previous attempts to facilitate the use of research in practice at the individual and organizational levels. Discussion The 6-month PEAK program consisted of four consecutive and interdependent components. First, leadership support was secured and electronic resources were acquired and distributed to participants. Next, a two-day training workshop consisting of didactic and small group activities was conducted that addressed the five steps of evidence based practice. For five months following the workshop, participants worked in small groups to review and synthesize literature around a group-selected area of common clinical interest. Each group contributed to the generation of a “Best Practices List” - a list of locally generated, evidence-based, actionable behaviors relevant to the groups’ clinical practice. Ultimately, participants agreed to implement the Best Practices List in their clinical practice. Summary This, first of two companion papers, describes the underlying pedagogical theories, knowledge translation frameworks, and research evidence used to derive the PEAK program

  9. Promoting physical therapists' of research evidence to inform clinical practice: part 1--theoretical foundation, evidence, and description of the PEAK program.

    Science.gov (United States)

    Tilson, Julie K; Mickan, Sharon

    2014-06-25

    There is a need for theoretically grounded and evidence-based interventions that enhance the use of research evidence in physical therapist practice. This paper and its companion paper introduce the Physical therapist-driven Education for Actionable Knowledge translation (PEAK) program, an educational program designed to promote physical therapists' integration of research evidence into clinical decision-making. The pedagogical foundations for the PEAK educational program include Albert Bandura's social cognitive theory and Malcolm Knowles's adult learning theory. Additionally, two complementary frameworks of knowledge translation, the Promoting Action on Research Implementation in Health Services (PARiHS) and Knowledge to Action (KTA) Cycle, were used to inform the organizational elements of the program. Finally, the program design was influenced by evidence from previous attempts to facilitate the use of research in practice at the individual and organizational levels. The 6-month PEAK program consisted of four consecutive and interdependent components. First, leadership support was secured and electronic resources were acquired and distributed to participants. Next, a two-day training workshop consisting of didactic and small group activities was conducted that addressed the five steps of evidence based practice. For five months following the workshop, participants worked in small groups to review and synthesize literature around a group-selected area of common clinical interest. Each group contributed to the generation of a "Best Practices List" - a list of locally generated, evidence-based, actionable behaviors relevant to the groups' clinical practice. Ultimately, participants agreed to implement the Best Practices List in their clinical practice. This, first of two companion papers, describes the underlying pedagogical theories, knowledge translation frameworks, and research evidence used to derive the PEAK program - an educational program designed to

  10. Use of reinforced soil foundation (RSF) to support shallow foundation : summary report.

    Science.gov (United States)

    2008-05-01

    This research study investigates the potential benefits of using reinforced soil foundations to improve the bearing capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 tests, including 38 la...

  11. Use of reinforced soil foundation (RSF) to support shallow foundation : final report, November 2008.

    Science.gov (United States)

    2008-11-01

    This research study aims at investigating the potential benefits of using reinforced soil foundations to improve the bearing capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 tests, includ...

  12. Use of reinforced soil foundation (RSF) to support shallow foundation : summary report, November 2008.

    Science.gov (United States)

    2008-05-01

    This research study investigates the potential benefits of using reinforced soil foundations to improve the bearing : capacity and reduce the settlement of shallow foundations on soils. To implement this objective, a total of 117 : tests, including 3...

  13. Justification of parameters and selection of equipment for laboratory researches of a rammer's operating element dynamics in a soil foundation of a tank for oil and oil products storage

    Science.gov (United States)

    Gruzin, A. V.; Gruzin, V. V.; Shalay, V. V.

    2017-08-01

    The development of technology for a directional soil compaction of tank foundations for oil and oil products storage is a relevant problem which solution will enable simultaneously provide required operational characteristics of a soil foundation and reduce time and material costs to prepare the foundation. The impact dynamics of rammers' operating elements on the soil foundation is planned to specify in the course of laboratory studies. A specialized technique is developed to justify the parameters and select the equipment for laboratory researches. The usage of this technique enabled us to calculate dimensions of the models, of a test bench and specifications of the recording equipment, and a lighting system. The necessary equipment for laboratory studies was selected. Preliminary laboratory tests were carried out. The estimate of accuracy for planned laboratory studies was given.

  14. Characteristic Behavior of Bucket Foundations

    DEFF Research Database (Denmark)

    Barari, Amin

    political and industrial forces(particularly in northern Europe) supporting the development of the offshore wind industry. The overall aim of the research presented in this thesis was to improve the design of offshore wind turbine foundations. The work was divided into two main researchefforts: geotechnical...... reduce the risks and costsrelated to offshore geotechnics. The thesis examines: 1.Characteristic Behavior of Bucket Foundations 2. Modeling of Water Flow through Porous Media The outcomes of each of the research contributions are summarized in four research articles, either directly or indirectly...... engineering experiments to gain insight into the behavior of offshore bucket foundations, and development of methods to improve the study of infiltration intounsaturated soils, an important problem in geo-environmental engineering. The outcomes of the research have the potential to directly or indirectly...

  15. A review of the International Brain Research Foundation novel approach to mild traumatic brain injury presented at the International Conference on Behavioral Health and Traumatic Brain Injury.

    Science.gov (United States)

    Polito, Mary Zemyan; Thompson, James W G; DeFina, Philip A

    2010-09-01

    "The International Conference on Behavioral Health and Traumatic Brain Injury" held at St. Joseph's Regional Medical Center in Paterson, NJ., from October 12 to 15, 2008, included a presentation on the novel assessment and treatment approach to mild traumatic brain injury (mTBI) by Philip A. DeFina, PhD, of the International Brain Research Foundation (IBRF). Because of the urgent need to treat a large number of our troops who are diagnosed with mTBI and post-traumatic stress disorder (PTSD), the conference was held to create a report for Congress titled "Recommendations to Improve the Care of Wounded Warriors NOW. March 12, 2009." This article summarizes and adds greater detail to Dr. DeFina's presentation on the current standard and novel ways to approach assessment and treatment of mTBI and PTSD. Pilot data derived from collaborative studies through the IBRF have led to the development of clinical and research protocols utilizing currently accepted, valid, and reliable neuroimaging technologies combined in novel ways to develop "neuromarkers." These neuromarkers are being evaluated in the context of an "Integrity-Deficit Matrix" model to demonstrate their ability to improve diagnostic accuracy, guide treatment programs, and possibly predict outcomes for patients suffering from traumatic brain injury.

  16. The New Forgotten Half and Research Directions to Support Them. Summary and Key Findings. A William T. Grant Foundation Inequality Paper

    Science.gov (United States)

    Rosenbaum, James; Ahearn, Caitlin; Becker, Kelly; Rosenbaum, Janet

    2015-01-01

    In 1988, the William T. Grant Foundation issued "The Forgotten Half," the final report of the Foundation's Commission on Youth and America's Future. Focusing on inequality in American society, specifically among non-college-bound 16-24 year olds, the report explored the challenges facing young people and the institutions that serve them.…

  17. The Impact of the GE Foundation "Developing Futures"™ in Education Program on Mathematics Performance Trends in Four Districts. Research Report # RR-74

    Science.gov (United States)

    Sirinides, Philip; Supovitz, Jonathan; Tognatta, Namrata; May, Henry

    2013-01-01

    Beginning in 2005, the GE Foundation initiated a commitment of expertise and financial resources to a set of urban school districts to improve public education and enhance student achievement in mathematics and science. This report analyzes the impacts of the GE Foundation commitment to the partner districts by examining trends in student…

  18. Cushing's Support and Research Foundation

    Science.gov (United States)

    ... high blood pressure, type II diabetes, polycystic ovarian syndrome, endometriosis, obesity, adult acne, metabolic disease, and panic attacks, but not Cushing's. After diagnosis and treatment, my weight is back to normal, and I ...

  19. Research Award: Foundations for Innovation

    International Development Research Centre (IDRC) Digital Library (Canada)

    Office 2004 Test Drive User

    adaptation, and uptake of STEM innovations in their place of origin? ... master's program in one of the following disciplines: economic geography, business, finance, economics, management, administration, sociology, regional science, urban.

  20. American Foundation for AIDS Research

    Science.gov (United States)

    ... WHO Support Pilot Study Investigating PrEP in the Philippines Other News and Features Breaking Her Silence We ... cost to you! About amfAR About HIV/AIDS Financial Information Donor Privacy Policy Terms of Use Sitemap ...

  1. Novel Hematopoietic Target Genes in the NRF2-Mediated Transcriptional Pathway

    Directory of Open Access Journals (Sweden)

    Michelle R. Campbell

    2013-01-01

    Full Text Available Nuclear factor- (erythroid-derived 2 like 2 (NFE2L2, NRF2 is a key transcriptional activator of the antioxidant response pathway and is closely related to erythroid transcription factor NFE2. Under oxidative stress, NRF2 heterodimerizes with small Maf proteins and binds cis-acting enhancer sequences found near oxidative stress response genes. Using the dietary isothiocyanate sulforaphane (SFN to activate NRF2, chromatin immunoprecipitation sequencing (ChIP-seq identified several hundred novel NRF2-mediated targets beyond its role in oxidative stress. Activated NRF2 bound the antioxidant response element (ARE in promoters of several known and novel target genes involved in iron homeostasis and heme metabolism, including known targets FTL and FTH1, as well as novel binding in the globin locus control region. Five novel NRF2 target genes were chosen for followup: AMBP, ABCB6, FECH, HRG-1 (SLC48A1, and TBXAS1. SFN-induced gene expression in erythroid K562 and lymphoid cells were compared for each target gene. NRF2 silencing showed reduced expression in lymphoid, lung, and hepatic cells. Furthermore, stable knockdown of NRF2 negative regulator KEAP1 in K562 cells resulted in increased NQO1, AMBP, and TBXAS1 expression. NFE2 binding sites in K562 cells revealed similar binding profiles as lymphoid NRF2 sites in all potential NRF2 candidates supporting a role for NRF2 in heme metabolism and erythropoiesis.

  2. Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous hypertension.

    Science.gov (United States)

    Li, Liwen; Pan, Hao; Wang, Handong; Li, Xiang; Bu, Xiaomin; Wang, Qiang; Gao, Yongyue; Wen, Guodao; Zhou, Yali; Cong, Zixiang; Yang, Youqing; Tang, Chao; Liu, Zhengwei

    2016-11-21

    Venous hypertension(VH) plays an important role in the pathogenesis of cerebral arteriovenous malformations (AVMs) and is closely associated with the HIF-1α/VEGF signaling pathway. Nuclear factor erythroid 2-related factor 2(Nrf2) significantly influences angiogenesis; however, the interplay between Nrf2 and VEGF under VH in brain AVMs remains unclear. Therefore, our study aimed to investigate the interplay between Nrf2 and VEGF due to VH in brain AVMs. Immunohistochemistry indicated that Nrf2 and VEGF were highly expressed in human brain AVM tissues. In vivo, we established a VH model in both wild-type (WT) and siRNA-mediated Nrf2 knockdown rats. VH significantly increased the expression of Nrf2 and VEGF. Loss of Nrf2 markedly inhibited the upregulation of VEGF, as determined by Western blot analysis and qRT-PCR. In vitro, primary brain microvascular endothelial cells (BMECs) were isolated from WT and Nrf2 -/- mice, and a VEGF-Nrf2 positive feed-back loop was observed in BMECs. By trans well assay and angiogenesis assay, Nrf2 knockout significantly inhibited the migration and vascular tube formation of BMECs. These findings suggest that the interplay between Nrf2 and VEGF can contribute to VH-induced angiogenesis in brain AVMs pathogenesis.

  3. Complexity of CNC transcription factors as revealed by gene targeting of the Nrf3 locus.

    Science.gov (United States)

    Derjuga, Anna; Gourley, Tania S; Holm, Teresa M; Heng, Henry H Q; Shivdasani, Ramesh A; Ahmed, Rafi; Andrews, Nancy C; Blank, Volker

    2004-04-01

    Cap'n'collar (CNC) family basic leucine zipper transcription factors play crucial roles in the regulation of mammalian gene expression and development. To determine the in vivo function of the CNC protein Nrf3 (NF-E2-related factor 3), we generated mice deficient in this transcription factor. We performed targeted disruption of two Nrf3 exons coding for CNC homology, basic DNA-binding, and leucine zipper dimerization domains. Nrf3 null mice developed normally and revealed no obvious phenotypic differences compared to wild-type animals. Nrf3(-/-) mice were fertile, and gross anatomy as well as behavior appeared normal. The mice showed normal age progression and did not show any apparent additional phenotype during their life span. We observed no differences in various blood parameters and chemistry values. We infected wild-type and Nrf3(-/-) mice with acute lymphocytic choriomeningitis virus and found no differences in these animals with respect to their number of virus-specific CD8 and CD4 T cells as well as their B-lymphocyte response. To determine whether the mild phenotype of Nrf3 null animals is due to functional redundancy, we generated mice deficient in multiple CNC factors. Contrary to our expectations, an absence of Nrf3 does not seem to cause additional lethality in compound Nrf3(-/-)/Nrf2(-/-) and Nrf3(-/-)/p45(-/-) mice. We hypothesize that the role of Nrf3 in vivo may become apparent only after appropriate challenge to the mice.

  4. The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism

    Directory of Open Access Journals (Sweden)

    Yoichiro eMitsuishi

    2012-12-01

    Full Text Available The Keap1-Nrf2 pathway plays a central role in the protection of cells against oxidative and xenobiotic stresses. Nrf2 is a potent transcription activator that recognizes a unique DNA sequence known as the antioxidant response element (ARE. Under normal conditions, Nrf2 binds to Keap1 in the cytoplasm, resulting in proteasomal degradation. Following exposure to electrophiles or reactive oxygen species, Nrf2 becomes stabilized, translocates into the nucleus and activates the transcription of various cytoprotective genes. Increasing attention has been paid to the role of Nrf2 in cancer cells because the constitutive stabilization of Nrf2 has been observed in many human cancers with poor prognosis. Recent studies have shown that the antioxidant and detoxification activities of Nrf2 confer chemo- and radio-resistance to cancer cells. In this review, we provide an overview of the Keap1-Nrf2 system and discuss its role under physiological and pathological conditions, including cancers. We also introduce the results of our recent study describing Nrf2 function in the metabolism of cancer cells. Nrf2 likely confers a growth advantage to cancer cells through enhancing cytoprotection and anabolism. Finally, we discuss the possible impact of Nrf2 inhibitors on cancer therapy.

  5. Foundations for renewables

    Energy Technology Data Exchange (ETDEWEB)

    Neidlein, H.C. [German Agency Scherer Schnell Walser und Partner (Germany)

    2007-07-01

    In Germany, 77 foundations promote renewable energy technology with around Euro 25 million annually. The most important internationally active foundations, however, can be found in the Anglo-Saxon countries. (orig.)

  6. Toxicology Education Foundation

    Science.gov (United States)

    ... bodies and our world. Welcome to the Toxicology Education Foundation! Our mission is to enhance public understanding ... In with us, follow our Tweets, choose Toxicology Education Foundation as your preferred charity through Smile.Amazon. ...

  7. Skin Cancer Foundation

    Science.gov (United States)

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the ... Handbook A "Sunscreen Gene"? Skin Cancer Facts & Statistics Skin Cancer Treatment Glossary Information on medications and procedures ...

  8. Robert Wood Johnson Foundation

    Science.gov (United States)

    Robert Wood Johnson Foundation Search How We Work Our Focus Areas About RWJF Search Menu How We Work Grants ... Learn more For Grantees and Grantseekers The Robert Wood Johnson Foundation funds a wide array of programs ...

  9. Schisandra chinensis regulates drug metabolizing enzymes and drug transporters via activation of Nrf2-mediated signaling pathway

    Directory of Open Access Journals (Sweden)

    He JL

    2014-12-01

    Full Text Available Jin-Lian He,1 Zhi-Wei Zhou,2,3 Juan-Juan Yin,2 Chang-Qiang He,1 Shu-Feng Zhou,2,3 Yang Yu1 1College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, People’s Republic of China Abstract: Drug metabolizing enzymes (DMEs and drug transporters are regulated via epigenetic, transcriptional, posttranscriptional, and translational and posttranslational modifications. Phase I and II DMEs and drug transporters play an important role in the disposition and detoxification of a large number of endogenous and exogenous compounds. The nuclear factor (erythroid-derived 2-like 2 (Nrf2 is a critical regulator of a variety of important cytoprotective genes that are involved in disposition and detoxification of xenobiotics. Schisandra chinensis (SC is a commonly used traditional Chinese herbal medicine that has been primarily used to protect the liver because of its potent antioxidative and anti-inflammatory activities. SC can modulate some DMEs and drug transporters, but the underlying mechanisms are unclear. In this study, we aimed to explore the role of Nrf2 in the regulatory effect of SC extract (SCE on selected DMEs and drug transporters in human hepatocellular liver carcinoma cell line (HepG2 cells. The results showed that SCE, schisandrin A, and schisandrin B significantly increased the expression of NAD(PH: Nicotinamide Adenine Dinucleotide Phosphate-oxidase or:quinone oxidoreductase 1, heme oxygenase-1, glutamate–cysteine ligase, and glutathione S-transferase A4 at both transcriptional and posttranscriptional levels. Incubation of HepG2 cells with SCE resulted in a significant

  10. Solar panel foundation device

    Energy Technology Data Exchange (ETDEWEB)

    Hawley, W.W.

    1983-03-29

    A transportable solar panel foundation device which has a bottom member, at least one upstanding side member, and an essentially open top. The side members are angled to permit nesting of a plurality of the foundation devices, and reinforcement pads are carried by the foundation device to support legs for one or more solar panels.

  11. Silencing Nrf2 impairs glioma cell proliferation via AMPK-activated mTOR inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Yue [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Wang, Handong, E-mail: njhdwang@hotmail.com [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Wang, Qiang [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Ding, Hui [Department of Neurosurgery, Jinling Hospital, School of Medicine, Southern Medical University (Guangzhou), 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China); Wu, Heming [Department of Neurosurgery, Nanjing Jingdu Hospital, No. 34, Biao 34, Yanggongjing Road, Nanjing 210002, Jiangsu Province (China); Pan, Hao [Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province (China)

    2016-01-15

    Gliomas are the leading cause of death among adults with primary brain malignancies. Treatment for malignant gliomas remains limited, and targeted therapies have been incompletely explored. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription regulator for antioxidant and detoxification enzymes, is abundantly expressed in cancer cells. In this study, the role and mechanism of Nrf2 in cancer cell proliferation was investigated in multiple glioma cell lines. We first evaluated the expression patterns of Nrf2 in four glioma cell lines and found all four cell lines expressed Nrf2, but the highest level was observed in U251 cells. We further evaluated the biological functions of Nrf2 in U251 glioma cell proliferation by specific inhibition of Nrf2 using short hairpin RNA (shRNA). We found that Nrf2 depletion inhibited glioma cell proliferation. Nrf2 depletion also decreased colony formation in U251 cells stably expressing Nrf2 shRNA compared to scrambled control shRNA. Moreover, suppression of Nrf2 expression could lead to ATP depletion (with concomitant rise in AMP/ATP ratio) and consequently to AMPK-activated mTOR inhibition. Finally, activation of adenosine monophosphate–activated protein kinase (AMPK) by treated with phenformin, an AMPK agonist, can mimic the inhibitory effect of Nrf2 knockdown in U251 cells. In conclusion, our findings will shed light to the role and mechanism of Nrf2 in regulating glioma proliferation via ATP-depletion-induced AMPK activation and consequent mTOR inhibition, a novel insight into our understanding the role and mechanism of Nrf2 in glioma pathoetiology. To our knowledge, this is also the first report to provide a rationale for the implication of cross-linking between Nrf2 and mTOR signaling.

  12. Inhibition of early T cell cytokine production by arsenic trioxide occurs independently of Nrf2.

    Directory of Open Access Journals (Sweden)

    Kelly R VanDenBerg

    Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is a stress-activated transcription factor that induces a variety of cytoprotective genes. Nrf2 also mediates immunosuppressive effects in multiple inflammatory models. Upon activation, Nrf2 dissociates from its repressor protein, Keap1, and translocates to the nucleus where it induces Nrf2 target genes. The Nrf2-Keap1 interaction is disrupted by the environmental toxicant and chemotherapeutic agent arsenic trioxide (ATO. The purpose of the present study was to determine the effects of ATO on early events of T cell activation and the role of Nrf2 in those effects. The Nrf2 target genes Hmox-1, Nqo-1, and Gclc were all upregulated by ATO (1-2 μM in splenocytes derived from wild-type, but not Nrf2-null, mice, suggesting that Nrf2 is activated by ATO in splenocytes. ATO also inhibited IFNγ, IL-2, and GM-CSF mRNA and protein production in wild-type splenocytes activated with the T cell activator, anti-CD3/anti-CD28. However, ATO also decreased production of these cytokines in activated splenocytes from Nrf2-null mice, suggesting the inhibition is independent of Nrf2. Interestingly, ATO inhibited TNFα protein secretion, but not mRNA expression, in activated splenocytes suggesting the inhibition is due to post-transcriptional modification. In addition, c-Fos DNA binding was significantly diminished by ATO in wild-type and Nrf2-null splenocytes activated with anti-CD3/anti-CD28, consistent with the observed inhibition of cytokine production by ATO. Collectively, this study suggests that although ATO activates Nrf2 in splenocytes, inhibition of early T cell cytokine production by ATO occurs independently of Nrf2 and may instead be due to impaired AP-1 DNA binding.

  13. Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level.

    Directory of Open Access Journals (Sweden)

    Xiao-Jun Wang

    Full Text Available The transcription factor Nrf2 is the master regulator of a cellular defense mechanism against environmental insults. The Nrf2-mediated antioxidant response is accomplished by the transcription of a battery of genes that encode phase II detoxifying enzymes, xenobiotic transporters, and antioxidants. Coordinated expression of these genes is critical in protecting cells from toxic and carcinogenic insults and in maintaining cellular redox homeostasis. Activation of the Nrf2 pathway is primarily controlled by Kelch-like ECH-associated protein 1 (Keap1, which is a molecular switch that turns on or off the Nrf2 signaling pathway according to intracellular redox conditions. Here we report our finding of a novel Nrf2 suppressor ectodermal-neural cortex 1 (ENC1, which is a BTB-Kelch protein and belongs to the same family as Keap1. Transient expression of ENC1 reduced steady-state levels of Nrf2 and its downstream gene expression. Although ENC1 interacted with Keap1 indirectly, the ENC1-mediated down-regulation of Nrf2 was independent of Keap1. The negative effect of ENC1 on Nrf2 was not due to a change in the stability of Nrf2 because neither proteasomal nor lysosomal inhibitors had any effects. Overexpression of ENC1 did not result in a change in the level of Nrf2 mRNA, rather, it caused a decrease in the rate of Nrf2 protein synthesis. These results demonstrate that ENC1 functions as a negative regulator of Nrf2 through suppressing Nrf2 protein translation, which adds another level of complexity in controlling the Nrf2 signaling pathway.

  14. Proceedings of the Annual Acquisition Research Symposium (2nd), Acquisition Research: The Foundation for Innovation, Held in Monterey, California on 18-19 May 2005

    Science.gov (United States)

    2005-05-01

    Frontiers of Entrepreneurship Research http://www.babson.edu/entrep/fer/papers95/hanks.html. Hardin, R. (1971, September). Collective action as an...sales representation and franchise laws for wrongful termination. It’s not the primary objective, but it’s a benefit. Nearly every comment...competitive sourcing, privatization initiatives, public-private partnerships, and franchising . The outcomes of such programs remain to be assessed, but

  15. From the NSF: The National Science Foundation's Investments in Broadening Participation in Science, Technology, Engineering, and Mathematics Education through Research and Capacity Building.

    Science.gov (United States)

    James, Sylvia M; Singer, Susan R

    The National Science Foundation (NSF) has a long history of investment in broadening participation (BP) in science, technology, engineering, and mathematics (STEM) education. A review of past NSF BP efforts provides insights into how the portfolio of programs and activities has evolved and the broad array of innovative strategies that has been used to increase the participation of groups underrepresented in STEM, including women, minorities, and persons with disabilities. While many are familiar with these long-standing programmatic efforts, BP is also a key component of NSF's strategic plans, has been highlighted in National Science Board reports, and is the focus of ongoing outreach efforts. The majority of familiar BP programs, such as the Louis Stokes Alliances for Minority Participation (now 25 years old), are housed in the Directorate for Education and Human Resources. However, fellowship programs such as the Graduate Research Fellowships and Postdoctoral Research Fellowships under the Directorate for Biological Sciences (and parallel directorates in other STEM disciplines) are frequently used to address underrepresentation in STEM disciplines. The FY2016 and FY2017 budget requests incorporate funding for NSF INCLUDES, a new cross-agency BP initiative that will build on prior successes while addressing national BP challenges. NSF INCLUDES invites the use of innovative approaches for taking evidence-based best practices to scale, ushering in a new era in NSF BP advancement. © 2016 S. M. James and S. R. Singer. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  16. The Reflective Foundation

    DEFF Research Database (Denmark)

    Lunde Jørgensen, Ida

    Private foundations and cultural philanthropy by élites is viewed with increasing skepticism in recent years, begging the question of the extent to which foundations reflect on their role vis a vis wider societal norms. Through the prism of the New Carlsberg Foundation, financed by the brewery...... Carlsberg A/S, the paper seeks to elucidate the way in which one culturally significant foundation from Denmark has reflected on - and legitimated - its work and investments at critical moments in the past decades. The paper indicates a foundation with a high degree of reflection on the wider societal...

  17. Environmental Foundations in Germany

    Directory of Open Access Journals (Sweden)

    Thomas Krikser

    2015-05-01

    Full Text Available Foundations in Germany were examined in the context of environmental issues. Data from environmental foundations show that there is huge difference between private and public foundations concerning financial settings. Furthermore, environment is often not the only objective and sometimes not even processed. Our analysis shows that there are different types of foundations with regard to environmental scopes and activities. Although “attractive topics” such as biodiversity and landscape conservation seem to be more important to foundations, less visible topics such as pollution prevention remain merely a “blind spot.” Together, these findings suggest that there is only a limited potential of private foundations compared with public foundations. Nevertheless, there might be an impact on environmental awareness and local sustainability.

  18. The role of Nrf1 and Nrf2 in the regulation of glutathione and redox dynamics in the developing zebrafish embryo

    Directory of Open Access Journals (Sweden)

    Karilyn E. Sant

    2017-10-01

    Full Text Available Redox signaling is important for embryogenesis, guiding pathways that govern processes crucial for embryo patterning, including cell polarization, proliferation, and apoptosis. Exposure to pro-oxidants during this period can be deleterious, resulting in altered physiology, teratogenesis, later-life diseases, or lethality. We previously reported that the glutathione antioxidant defense system becomes increasingly robust, including a doubling of total glutathione and dynamic shifts in the glutathione redox potential at specific stages during embryonic development in the zebrafish, Danio rerio. However, the mechanisms underlying these changes are unclear, as is the effectiveness of the glutathione system in ameliorating oxidative insults to the embryo at different stages. Here, we examine how the glutathione system responds to the model pro-oxidants tert-butylhydroperoxide and tert-butylhydroquinone at different developmental stages, and the role of Nuclear factor erythroid 2-related factor (Nrf proteins in regulating developmental glutathione redox status. Embryos became increasingly sensitive to pro-oxidants after 72 h post-fertilization (hpf, after which the duration of the recovery period for the glutathione redox potential was increased. To determine whether the doubling of glutathione or the dynamic changes in glutathione redox potential are mediated by zebrafish paralogs of Nrf transcription factors, morpholino oligonucleotides were used to knock down translation of Nrf1 and Nrf2 (nrf1a, nrf1b, nrf2a, nrf2b. Knockdown of Nrf1a or Nrf1b perturbed glutathione redox state until 72 hpf. Knockdown of Nrf2 paralogs also perturbed glutathione redox state but did not significantly affect the response of glutathione to pro-oxidants. Nrf1b morphants had decreased gene expression of glutathione synthesis enzymes, while hsp70 increased in Nrf2b morphants. This work demonstrates that despite having a more robust glutathione system, embryos become more

  19. Student Contributions to Citizen Science Programs As a Foundation for Independent and Classroom-Based Undergraduate Research in the Earth Sciences

    Science.gov (United States)

    Guertin, L. A.

    2014-12-01

    Environmental monitoring projects on the grounds of a campus can serve as data collection sites for undergraduate research. Penn State Brandywine has utilized students in independent study projects to establish two citizen science programs and to begin collecting data, with the data sets serving as a foundation for authentic inquiry-based exercises in introductory-level Earth science courses. The first citizen science program is The Smithsonian Institution's Global Tree Banding Project, which contributes to research about tree biomass by tracking how trees respond to climate. We are going beyond the requirements of the Smithsonian project. Instead of only taking two measurements each in the spring and fall, undergraduate researchers are taking measurements every two weeks throughout the year. We started taking measurements of ten trees on campus in 2012 will continue until each tree outgrows its tree band. The data is available for download in Google Spreadsheets for students to examine changes in tree diameter within one or between growing seasons, supplemented with temperature and precipitation data (see http://sites.psu.edu/treebanding/). A second citizen science program we have begun on campus is the NASA-funded Digital Earth Watch (DEW) Picture Post Project, allowing students to monitor the environment and share observations through digital photography. We established four Picture Post sites on campus, with students taking weekly photos to establish an environmental baseline of the campus landscape and to document future environmental changes pre- and post-construction. We started taking digital photos on campus in 2014 will continue well past the completion of construction to continue to look for changes. The image database is less than a year old, but the images provide enough information for some early analyses, such as the variations in "greenness" over the seasons. We have created a website that shares the purpose of our participation in the Picture Post

  20. Report for fiscal 2000 on surveys on foundation to establish industrial technology strategy. Surveys on foundation to assist activation of research and development; 2000 nendo sangyo gijutsu senryaku sakutei kiban chosa hokokusho. Kenkyu kaihatsu kasseika shien kiso chosa

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    In order to help discuss the measures to activate researches and developments in private corporations, surveys were made on barriers and factors related to industrial technology research and development by fields, and discussions were given on structuring research and development models. Factors impeding research and development processes relate to a case of each phase in the fundamental research, applied research, and product development, and a case of human resources, funds and information. A policy of structuring models was determined to make quantitative the effects of different aiding systems of the government for researches and developments in private corporations. Case analyses were conducted by using a pilot model. In the present research, a questionnaire survey was carried out to acquire such data as R and D time lag, and to identify the effects of the policies. Surveys were also performed on research and development programs in North America, by making interviews to concerned corporations. As a result of the surveys, such problems were extracted as research and development fund, freer flow of human resources, research and development systems, handling of results of researches performed by consortiums, accounting systems, and sale of the government owned patents. (NEDO)

  1. Foundations of quantum gravity

    CERN Document Server

    Lindesay, James

    2013-01-01

    Exploring how the subtleties of quantum coherence can be consistently incorporated into Einstein’s theory of gravitation, this book is ideal for researchers interested in the foundations of relativity and quantum physics. The book examines those properties of coherent gravitating systems that are most closely connected to experimental observations. Examples of consistent co-gravitating quantum systems whose overall effects upon the geometry are independent of the coherence state of each constituent are provided, and the properties of the trapping regions of non-singular black objects, black holes, and a dynamic de Sitter cosmology are discussed analytically, numerically, and diagrammatically. The extensive use of diagrams to summarise the results of the mathematics enables readers to bypass the need for a detailed understanding of the steps involved. Assuming some knowledge of quantum physics and relativity, the book provides textboxes featuring supplementary information for readers particularly interested ...

  2. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    International Nuclear Information System (INIS)

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-01-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  3. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D., E-mail: cklaasse@kumc.edu

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  4. Clinical Outcome Assessments: Conceptual Foundation-Report of the ISPOR Clinical Outcomes Assessment - Emerging Good Practices for Outcomes Research Task Force.

    Science.gov (United States)

    Walton, Marc K; Powers, John H; Hobart, Jeremy; Patrick, Donald; Marquis, Patrick; Vamvakas, Spiros; Isaac, Maria; Molsen, Elizabeth; Cano, Stefan; Burke, Laurie B

    2015-09-01

    An outcome assessment, the patient assessment used in an endpoint, is the measuring instrument that provides a rating or score (categorical or continuous) that is intended to represent some aspect of the patient's health status. Outcome assessments are used to define efficacy endpoints when developing a therapy for a disease or condition. Most efficacy endpoints are based on specified clinical assessments of patients. When clinical assessments are used as clinical trial outcomes, they are called clinical outcome assessments (COAs). COAs include any assessment that may be influenced by human choices, judgment, or motivation. COAs must be well-defined and possess adequate measurement properties to demonstrate (directly or indirectly) the benefits of a treatment. In contrast, a biomarker assessment is one that is subject to little, if any, patient motivational or rater judgmental influence. This is the first of two reports by the ISPOR Clinical Outcomes Assessment - Emerging Good Practices for Outcomes Research Task Force. This report provides foundational definitions important for an understanding of COA measurement principles. The foundation provided in this report includes what it means to demonstrate a beneficial effect, how assessments of patients relate to the objective of showing a treatment's benefit, and how these assessments are used in clinical trial endpoints. In addition, this report describes intrinsic attributes of patient assessments and clinical trial factors that can affect the properties of the measurements. These factors should be considered when developing or refining assessments. These considerations will aid investigators designing trials in their choice of using an existing assessment or developing a new outcome assessment. Although the focus of this report is on the development of a new COA to define endpoints in a clinical trial, these principles may be applied more generally. A critical element in appraising or developing a COA is to

  5. Characteristic Behavior of Bucket Foundations

    DEFF Research Database (Denmark)

    Barari, Amin

    and gas industry and have recently been used in offshore wind turbines. The bucket foundation is a welded steel structure consisting of a tubular center column connected to a steel bucket through flange-reinforced stiffeners. The overall aim of the research presented in this thesis was to improve...

  6. Corporate Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Thomsen, Steen

    1999-01-01

    to be relatively inefficient since they lack monitoring by residual claimants and access to equity finance from the stock market. Nevertheless, empirical research (Thomsen 1996) has found that Danish foundation-owned companies do no worse in terms of profitability and growth than companies with dispersed ownership...

  7. Theoretical foundations for collaboration engineering

    NARCIS (Netherlands)

    Kolfschoten, G.L.

    2007-01-01

    Collaboration is often presented as the solution to numerous problems in business and society. However, collaboration is challenging, and collaboration support is not an off-the-shelf-product. This research offers theoretical foundations for Collaboration Engineering. Collaboration Engineering is an

  8. Cornelia de Lange Syndrome Foundation

    Science.gov (United States)

    ... Outside Links Privacy & Terms Site Map The Cornelia de Lange Syndrome (CdLS) Foundation is a family support organization that ... research into the causes and manifestations of the syndrome, and help people with a diagnosis of CdLS make informed decisions throughout their lives.

  9. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer

    Directory of Open Access Journals (Sweden)

    Tatsuhiro Shibata

    2011-09-01

    Full Text Available Esophageal squamous cancer (ESC is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22% in advanced ESC tumors and ESC cell lines (3/10. The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT.

  10. CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

    Science.gov (United States)

    Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

    2015-04-01

    The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

  11. Enhanced B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation contributes to ABCC1-mediated chemoresistance and glutathione-mediated survival in acquired topoisomerase II poison-resistant cancer cells.

    Science.gov (United States)

    Chen, Huang-Hui; Chang, Hsin-Huei; Chang, Jang-Yang; Tang, Ya-Chu; Cheng, Yung-Chi; Lin, Li-Mei; Cheng, Shu-Ying; Huang, Chih-Hsiang; Sun, Man-Wu; Chen, Chiung-Tong; Kuo, Ching-Chuan

    2017-12-01

    Nuclear factor erythroid-2-related factor 2 (NRF2) mainly regulates transcriptional activation through antioxidant-responsive elements (AREs) present in the promoters of NRF2 target genes. Recently, we found that NRF2 was overexpressed in a KB-derived drug-resistant cancer cell panel. In this panel, KB-7D cells, which show acquired resistance to topoisomerase II (Top II) poisons, exhibited the highest NRF2 activation. To investigate whether NRF2 directly contributed to acquired resistance against Top II poisons, we manipulated NRF2 by genetic and pharmacological approaches. The result demonstrated that silencing of NRF2 by RNA interference increased the sensitivity and treatment with NRF2 activator decreased the sensitivity of KB and KB-7D cells toward Top II poisons. Further, increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation activated NRF2 signaling in KB-7D cells. Moreover, increased binding of NRF2 to an ARE in the promoter of ATP-binding cassette subfamily C member 1 (ABCC1) directly contributed to Top II poison resistance. In addition, activation of NRF2 increased glutathione level and antioxidant capacity in KB-7D cells compared with that in KB cells; moreover, high glutathione level provided survival advantage to KB-7D cells. Our study is the first to show that aberrant NRF2 activation is via increased B-Raf-mediated NRF2 gene transcription and HATs-mediated NRF2 protein acetylation, which increases the acquired resistance and promote the survival of Top II poison-resistant cancer cells. Importantly, NRF2 downstream effectors ABCC1 and glutathione directly contribute to acquired resistance and survival, respectively. These results suggest that blockade of NRF2 signaling may enhance therapeutic efficacy and reduce the survival of Top II poison-refractory tumors in clinical. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Shells on elastic foundations

    International Nuclear Information System (INIS)

    Das, Y.C.; Kedia, K.K.

    1977-01-01

    No realistic analytical work in the area of Shells on Elastic Foundations has been reported in the literature. Various foundation models have been proposed by several authors. These models involve one or more than one parameters to characterise the foundation medium. Some of these models cannot be used to derive the basic equations governing the behaviour of shells on elastic foundations. In the present work, starting from an elastic continuum hypothesis, a mathematical model for foundation has been derived in curvilinear orthogonal coordinates by the help of principle of virtual displacements, treating one of the virtual displacements as known to satisfy certain given conditions at its edge surfaces. In this model, several foundation parameters can be considered and it can also be used for layered medium of both finite and infinite thickness. (Auth.)

  13. [Analysis on Research Projects Supported by the National Natural Science Foundation of China at the National Institute of Parasitic Diseases during 2003-2013].

    Science.gov (United States)

    Zhou, Xiao-jun; Zheng, Bin; Yi, Feng-yun; Xiong, Yan-hong; Zhang, Min-qi

    2015-04-01

    The data of the National Natural Science Foundation (NSFC) projests obtained by the National Institute of Parasitic Diseases (NIPD), Chinese Center for Disease Control and Prevention (China CDC) during 2003-2013 were collected from internet-based science information system of NSFC, and NSFC search tool of Dingxiang Garden (http://nsfc.biomart.cn/). The number of funded projects, their subject classification and approved amount were analyzed, and compared with the other institutes of China CDC. Furthermore, the rationalization proposals were given in order to enhance the level of foundation management in the future.

  14. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    Energy Technology Data Exchange (ETDEWEB)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Mattson, Mark P. [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States); Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Camandola, Simonetta, E-mail: camandolasi@mail.nih.gov [Laboratory of Neurosciences, National Institute on Aging, Intramural Research Program, 251 Bayview Blvd., Baltimore, MD 21224 (United States)

    2013-04-19

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity.

  15. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

    International Nuclear Information System (INIS)

    Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng; Greig, Nigel H.; Mattson, Mark P.; Camandola, Simonetta

    2013-01-01

    Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity

  16. Training for Quality: Improving Early Childhood Programs through Systematic Inservice Training. Monographs of the High/Scope Educational Research Foundation, Number Nine.

    Science.gov (United States)

    Epstein, Ann S.

    The Training of Trainers (ToT) Evaluation investigated the efficacy of the High/Scope model for improving the quality of early childhood programs on a national scale. To address this question, the High/Scope Foundation undertook a multimethod evaluation that collected anecdotal records from the consultants and 793 participants in 40 ToT projects,…

  17. Induction of Mrp3 and Mrp4 transporters during acetaminophen hepatotoxicity is dependent on Nrf2

    International Nuclear Information System (INIS)

    Aleksunes, Lauren M.; Slitt, Angela L.; Maher, Jonathan M.; Augustine, Lisa M.; Goedken, Michael J.; Chan, Jefferson Y.; Cherrington, Nathan J.; Klaassen, Curtis D.; Manautou, Jose E.

    2008-01-01

    The transcription factor NFE2-related factor 2 (Nrf2) mediates detoxification and antioxidant gene transcription following electrophile exposure and oxidative stress. Mice deficient in Nrf2 (Nrf2-null) are highly susceptible to acetaminophen (APAP) hepatotoxicity and exhibit lower basal and inducible expression of cytoprotective genes, including NADPH quinone oxidoreductase 1 (Nqo1) and glutamate cysteine ligase (catalytic subunit, or Gclc). Administration of toxic APAP doses to C57BL/6J mice generates electrophilic stress and subsequently increases levels of hepatic Nqo1, Gclc and the efflux multidrug resistance-associated protein transporters 1-4 (Mrp1-4). It was hypothesized that induction of hepatic Mrp1-4 expression following APAP is Nrf2 dependent. Plasma and livers from wild-type (WT) and Nrf2-null mice were collected 4, 24 and 48 h after APAP. As expected, hepatotoxicity was greater in Nrf2-null compared to WT mice. Gene and protein expression of Mrp1-4 and the Nrf2 targets, Nqo1 and Gclc, was measured. Induction of Nqo1 and Gclc mRNA and protein after APAP was dependent on Nrf2 expression. Similarly, APAP treatment increased hepatic Mrp3 and Mrp4 mRNA and protein in WT, but not Nrf2-null mice. Mrp1 was induced in both genotypes after APAP, suggesting that elevated expression of this transporter was independent of Nrf2. Mrp2 was not induced in either genotype at the mRNA or protein levels. These results show that Nrf2 mediates induction of Mrp3 and Mrp4 after APAP but does not affect Mrp1 or Mrp2. Thus coordinated regulation of detoxification enzymes and transporters by Nrf2 during APAP hepatotoxicity is a mechanism by which hepatocytes may limit intracellular accumulation of potentially toxic chemicals

  18. Establishing a University Foundation.

    Science.gov (United States)

    Lemish, Donald L.

    A handbook on how to establish a university foundation is presented. It presupposes that a foundation will be used as the umbrella organization for receiving all private gifts, restricted and unrestricted, for the benefit of a public college or university; and hence it chiefly addresses readers from public colleges and universities. Information is…

  19. Foundations for Critical Thinking

    Science.gov (United States)

    Bers, Trudy; Chun, Marc; Daly, William T.; Harrington, Christine; Tobolowsky, Barbara F.

    2015-01-01

    "Foundations for Critical Thinking" explores the landscape of critical-thinking skill development and pedagogy through foundational chapters and institutional case studies involving a range of students in diverse settings. By establishing a link between active learning and improved critical thinking, this resource encourages all higher…

  20. Modelling Foundations and Applications

    DEFF Research Database (Denmark)

    This book constitutes the refereed proceedings of the 8th European Conference on Modelling Foundations and Applications, held in Kgs. Lyngby, Denmark, in July 2012. The 20 revised full foundations track papers and 10 revised full applications track papers presented were carefully reviewed...

  1. The Monopod Bucket Foundation

    DEFF Research Database (Denmark)

    Bakmar, Christian LeBlanc; Ahle, Kim; Nielsen, Søren A.

    2009-01-01

    Following the successful installation of a prototype of a monopod bucket foundation, also called a “monopod suction caisson”, at Horns Rev 2 Offshore Wind Farm, Denmark, in 2009, DONG Energy is currently developing a commercialization strategy. The monopod bucket foundation is a promising...

  2. The Jan Korec Foundation

    International Nuclear Information System (INIS)

    2007-01-01

    In this video-film activities of the the Jan Korec Foundation are presented. The Jan Korec Foundation supports students of technical sciences, sport activities, science and support of book publishing, humanitarian supports, the environment protection as well as support of different social projects.

  3. Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy

    Directory of Open Access Journals (Sweden)

    Priyanka Basak

    Full Text Available The Nuclear factor erythroid2-related factor2 (Nrf2, a master regulator of redox homoeostasis, is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes. It protects organs from various kinds of toxic insults. On the other hand, activation of Nrf2 is also correlated with cancer progression and chemoresistance. Downregulation of Nrf2 activity has attracted an increasing amount of attention as it may provide an alternative cancer therapy. In this review, we examine recent studies on roles of Nrf2 in several pathophysiological conditions emphasising cancer. We discuss elaborately the current knowledge on Nrf2 regulation including KEAP1-dependent and KEAP1-independent cascades. KEAP1/Nrf2 system is a master regulator of cellular response against a variety of environmental stresses. We also highlight several tightly controlled regulations of Nrf2 by numerous proteins, small molecules, toxic metals, etc. In addition, we evaluate the possible therapeutic approaches of increasing chemosensitivity via modulating Nrf2 signaling. Keywords: Nrf2, Transcription factor, KEAP1, Oxidative stress, Cell proliferation, Carcinogenesis, Chemoprevention

  4. Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Fiona Kerr

    2017-03-01

    Full Text Available Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD. Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding of the mechanisms mediating Nrf2 inhibition in neurodegenerative conditions may therefore direct the design of drugs targeted for the prevention of these diseases with minimal side-effects. Our study provides the first in vivo evidence that specific inhibition of Keap1, a negative regulator of Nrf2, can prevent neuronal toxicity in response to the AD-initiating Aβ42 peptide, in correlation with Nrf2 activation. Comparatively, lithium, an inhibitor of the Nrf2 suppressor GSK-3, prevented Aβ42 toxicity by mechanisms independent of Nrf2. A new direct inhibitor of the Keap1-Nrf2 binding domain also prevented synaptotoxicity mediated by naturally-derived Aβ oligomers in mouse cortical neurons. Overall, our findings highlight Keap1 specifically as an efficient target for the re-activation of Nrf2 in AD, and support the further investigation of direct Keap1 inhibitors for the prevention of neurodegeneration in vivo.

  5. DNA demethylation upregulated Nrf2 expression in Alzheimer's disease cellular model

    Directory of Open Access Journals (Sweden)

    Huimin eCao

    2016-01-01

    Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is an important transcription factor in the defense against oxidative stress. Cumulative evidence has shown that oxidative stress plays a key role in the pathogenesis of Alzheimer's disease (AD. Previous animal and clinical studies had observed decreased expression of Nrf2 in AD. However, the underlying regulation mechanisms of Nrf2 in AD remain unclear. Here, we used the DNA methyltransferases (Dnmts inhibitor 5-aza-2′-deoxycytidine (5-Aza to test whether Nrf2 expression was regulated by methylation in N2a cells characterizing by expressing human Swedish mutant amyloid precursor protein (N2a/APPswe. We found 5-Aza treatment increased Nrf2 at both mRNA and protein levels via down-regulating the expression of Dnmts and DNA demethylation. In addition, 5-Aza mediated upregulation of Nrf2 expression was concomitant with increased nuclear translocation of Nrf2 and higher expression of Nrf2 downstream target gene NAD(PH:quinone oxidoreductas (NQO1. Our study showed that DNA demethylation promoted the Nrf2 cell signaling pathway, which may enhance the antioxidant system against AD development.

  6. NRF2 deficiency replicates transcriptomic changes in Alzheimer's patients and worsens APP and TAU pathology

    Directory of Open Access Journals (Sweden)

    Ana I. Rojo

    2017-10-01

    Full Text Available Failure to translate successful neuroprotective preclinical data to a clinical setting in Alzheimer's disease (AD indicates that amyloidopathy and tauopathy alone provide an incomplete view of disease. We have tested here the relevance of additional homeostatic deviations that result from loss of activity of transcription factor NRF2, a crucial regulator of multiple stress responses whose activity declines with ageing. A transcriptomic analysis demonstrated that NRF2-KO mouse brains reproduce 7 and 10 of the most dysregulated pathways of human ageing and AD brains, respectively. Then, we generated a mouse that combines amyloidopathy and tauopathy with either wild type (AT-NRF2-WT or NRF2-deficiency (AT-NRF2-KO. AT-NRF2-KO brains presented increased markers of oxidative stress and neuroinflammation as well as higher levels of insoluble phosphorylated-TAU and Aβ*56 compared to AT-NRF2-WT mice. Young adult AT-NRF2-KO mice exhibited deficits in spatial learning and memory and reduced long term potentiation in the perforant pathway. This study demonstrates the relevance of normal homeostatic responses that decline with ageing, such as NRF2 activity, in the protection against proteotoxic, inflammatory and oxidative stress and provide a new strategy to fight AD.

  7. Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway.

    Science.gov (United States)

    Son, Tae Gen; Kawamoto, Elisa M; Yu, Qian-Sheng; Greig, Nigel H; Mattson, Mark P; Camandola, Simonetta

    2013-04-19

    Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal and glial cultures, and protects neurons against glutamate-induced excitotoxicity. Published by Elsevier Inc.

  8. Nitroxide delivery system for Nrf2 activation and skin protection.

    Science.gov (United States)

    Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Sasson, Shmuel Ben; Bianco-Peled, Havazelet; Bitton, Ronit; Kohen, Ron

    2015-08-01

    Cyclic nitroxides are a large group of compounds composed of diverse stable radicals also known as synthetic antioxidants. Although nitroxides are valuable for use in several skin conditions, in in vivo conditions they have several drawbacks, such as nonspecific dispersion in normal tissue, preferential renal clearance and rapid reduction of the nitroxide to the corresponding hydroxylamine. However, these drawbacks can be easily addressed by encapsulating the nitroxides within microemulsions. This approach would allow nitroxide activity and therefore their valuable effects (e.g. activation of the Keap1-Nrf2-EpRE pathway) to continue. In this work, nitroxides were encapsulated in a microemulsion composed of biocompatible ingredients. The nanometric size and shape of the vehicle microemulsion and nitroxide microemulsion displayed high similarity, indicating that the stability of the microemulsions was preserved. Our studies demonstrated that nitroxide microemulsions were more potent inducers of the Keap1-Nrf2-EpRE pathway than the free nitroxides, causing the activation of phase II enzymes. Moreover, microemulsions containing nitroxides significantly reduced UVB-induced cytotoxicity in the skin. Understanding the mechanism of this improved activity may expand the usage of many other Nrf2 modulating molecules in encapsulated form, as a skin protection strategy against oxidative stress-related conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Arduino Based Weather Monitoring Telemetry System Using NRF24L01+

    Science.gov (United States)

    Sidqi, Rafi; Rio Rynaldo, Bagus; Hadi Suroso, Satya; Firmansyah, Rifqi

    2018-04-01

    Abstract-Weather is an important part of the natural environment, thus knowing weather information is needed before doing activity. The main purpose of this research was to develop a weather monitoring system which capable to transmit weather data via radio frequency by using nRF24L01+ 2,4GHz radio module. This research implement Arduino UNO as the main controller of the system which send data wirelessly using the radio module and received by a receiver system. Received data then logged and displayed using a Graphical User Interface on a personal computer. Test and experiment result show that the system was able to transmit weather data via radio wave with maximum transmitting range of 32 meters.

  10. Introductory guide to foundations

    CSIR Research Space (South Africa)

    Donaldson, GW

    1973-01-01

    Full Text Available . The secret of successful foundations is knowing just how much the subsoil can support. As one goes deeper, the ability of the ground to support a load becomes greater so that the foundation engineer can choose between deep foundations and the expense... beginstoinaease. When the house is ~ ~ p l e t e d it shelters the gmund f f ~ m sun and wind and the moisture content i- wen more rapidly- Leaking pipes and sewers increase the volume of water fed to the clay while ornamental trees planted around the house...

  11. Dihydro-CDDO-trifluoroethyl amide suppresses inflammatory responses in macrophages via activation of Nrf2

    International Nuclear Information System (INIS)

    Li, Bin; Abdalrahman, Akram; Lai, Yimu; Janicki, Joseph S.; Ward, Keith W.; Meyer, Colin J.; Wang, Xing Li; Tang, Dongqi; Cui, Taixing

    2014-01-01

    Highlights: • Dh404 suppresses the expression of a selected set of pro-inflammatory cytokines in inflamed macrophages via activating Nrf2. • Dh404 activates Nrf2 while keeping Keap1 function intact in macrophages. • Dh404 minimally regulates NF-κB pathway in macrophages. - Abstract: Nuclear factor erythroid 2-related factor (Nrf2) is the major regulator of cellular defenses against various pathological stresses in a variety of organ systems, thus Nrf2 has evolved to be an attractive drug target for the treatment and/or prevention of human disease. Several synthetic oleanolic triterpenoids including dihydro-CDDO-trifluoroethyl amide (dh404) appear to be potent activators of Nrf2 and exhibit chemopreventive promises in multiple disease models. While the pharmacological efficacy of Nrf2 activators may be dependent on the nature of Nrf2 activation in specific cell types of target organs, the precise role of Nrf2 in mediating biological effects of Nrf2 activating compounds in various cell types remains to be further explored. Herein we report a unique and Nrf2-dependent anti-inflammatory profile of dh404 in inflamed macrophages. In lipopolysaccharide (LPS)-inflamed RAW264.7 macrophages, dh404 dramatically suppressed the expression of pro-inflammatory cytokines including inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β), while minimally regulating the expression of interleulin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNFα). Dh404 potently activated Nrf2 signaling; however, it did not affect LPS-induced NF-κB activity. Dh404 did not interrupt the interaction of Nrf2 with its endogenous inhibitor Kelch-like ECH associating protein 1 (Keap1) in macrophages. Moreover, knockout of Nrf2 blocked the dh404-induced anti-inflammatory responses in LPS-inflamed macrophages. These results demonstrated that dh404 suppresses pro-inflammatory responses in macrophages via an activation

  12. Nrf2 and Keap1 Abnormalities in 104 Lung Adenocarcinoma Cases and Association with Clinicopathologic Features

    Directory of Open Access Journals (Sweden)

    Yu XIAO

    2018-03-01

    Full Text Available Background and objective There are significantly interindividual variations of the expression level of nuclear factor erythroid-2-related factor 2 (Nrf2 and/or Kelch-like ECH-associated protein 1 (Keap1 in our previous studies. It has been proven that Nrf2 or Keap1 is related to resistance of chemotherapeutic drugs and/or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs. However, the expression of Nrf2 and Keap1 in lung adenocarcinoma patients with different “driver gene” is not clear. The aim of this study is to investigate the protein expression level of Nrf2 and Keap1 in lung adenocarcinoma and to elucidate the correlation between Nrf2 or Keap1 expression and the status of EGFR gene mutation and to determine the effects of Nrf2 and Keap1 on the patients. Methods Immunohistochemical analysis of Nrf2 and Keap1 in tumor specimens was performed in a total of 104 lung adenocarcinoma patients with the status of EGFR gene mutations or EGFR wide-type. Results The Nrf2 positive rate was 71.2% and Keap1 high expression rate was 34.6% in 104 patients. The Nrf2 positive rate significantly correlated with gender, stage and status of EGFR gene mutation (P0.05. The high expression of Keap1 was not significantly correlated with gender, age, smoking, differentiation, subtype of lung adenocarcinoma and status of EGFR gene mutation (P>0.05. The progression -free survival (PFS and overall survival (OS of the patients treated by EGFR-TKIs were significantly correlated with the expression level of Nrf2, but not with Keap1. The PFS and OS of the patients with Nrf2 high expression were significantly shorter than the patients with low/negative expression (P<0.05. Furthermore, Nrf2 high expression was the independent predictive factor for EGFR-TKIs induced PFS and OS (P<0.05. Conclusion The Nrf2 positive rate significantly correlated with the status of EGFR gene mutation in lung adenocarcinoma. The Nrf2 high expression significantly

  13. Dihydro-CDDO-trifluoroethyl amide suppresses inflammatory responses in macrophages via activation of Nrf2

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Abdalrahman, Akram; Lai, Yimu; Janicki, Joseph S. [Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Ward, Keith W.; Meyer, Colin J. [Department of Pharmacology, Reata Pharmaceuticals, Inc., Irving, TX 75063 (United States); Wang, Xing Li [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Tang, Dongqi, E-mail: Dongqi.Tang@uscmed.sc.edu [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States); Cui, Taixing, E-mail: taixing.cui@uscmed.sc.edu [Shandong University Qilu Hospital Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital of Shandong University, Jinan 250012 (China); Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC 29208 (United States)

    2014-02-21

    Highlights: • Dh404 suppresses the expression of a selected set of pro-inflammatory cytokines in inflamed macrophages via activating Nrf2. • Dh404 activates Nrf2 while keeping Keap1 function intact in macrophages. • Dh404 minimally regulates NF-κB pathway in macrophages. - Abstract: Nuclear factor erythroid 2-related factor (Nrf2) is the major regulator of cellular defenses against various pathological stresses in a variety of organ systems, thus Nrf2 has evolved to be an attractive drug target for the treatment and/or prevention of human disease. Several synthetic oleanolic triterpenoids including dihydro-CDDO-trifluoroethyl amide (dh404) appear to be potent activators of Nrf2 and exhibit chemopreventive promises in multiple disease models. While the pharmacological efficacy of Nrf2 activators may be dependent on the nature of Nrf2 activation in specific cell types of target organs, the precise role of Nrf2 in mediating biological effects of Nrf2 activating compounds in various cell types remains to be further explored. Herein we report a unique and Nrf2-dependent anti-inflammatory profile of dh404 in inflamed macrophages. In lipopolysaccharide (LPS)-inflamed RAW264.7 macrophages, dh404 dramatically suppressed the expression of pro-inflammatory cytokines including inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1 beta (MIP-1β), while minimally regulating the expression of interleulin-6 (IL-6), IL-1β, and tumor necrosis factor alpha (TNFα). Dh404 potently activated Nrf2 signaling; however, it did not affect LPS-induced NF-κB activity. Dh404 did not interrupt the interaction of Nrf2 with its endogenous inhibitor Kelch-like ECH associating protein 1 (Keap1) in macrophages. Moreover, knockout of Nrf2 blocked the dh404-induced anti-inflammatory responses in LPS-inflamed macrophages. These results demonstrated that dh404 suppresses pro-inflammatory responses in macrophages via an activation

  14. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    International Nuclear Information System (INIS)

    Jing, Xu; Ren, Dongmei; Wei, Xinbing; Shi, Huanying; Zhang, Xiumei; Perez, Ruth G.; Lou, Haiyan; Lou, Hongxiang

    2013-01-01

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury

  15. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Xu [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Ren, Dongmei [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China); Wei, Xinbing; Shi, Huanying; Zhang, Xiumei [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Perez, Ruth G. [Health Science Center, Paul L. Foster School of Medicine, Texas Tech University, El Paso, TX, 79905 (United States); Lou, Haiyan, E-mail: louhaiyan@sdu.edu.cn [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Lou, Hongxiang [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China)

    2013-12-15

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury.

  16. Cytoprotective Role of Nrf2 in Electrical Pulse Stimulated C2C12 Myotube.

    Directory of Open Access Journals (Sweden)

    Masaki Horie

    Full Text Available Regular physical exercise is central to a healthy lifestyle. However, exercise-related muscle contraction can induce reactive oxygen species and reactive nitrogen species (ROS/RNS production in skeletal muscle. The nuclear factor-E2-related factor-2 (Nrf2 transcription factor is a cellular sensor for oxidative stress. Regulation of nuclear Nrf2 signaling regulates antioxidant responses and protects organ structure and function. However, the role of Nrf2 in exercise- or contraction-induced ROS/RNS production in skeletal muscle is not clear. In this study, using differentiated C2C12 cells and electrical pulse stimulation (EPS of muscle contraction, we explored whether Nrf2 plays a role in the skeletal muscle response to muscle contraction-induced ROS/RNS. We found that EPS (40 V, 1 Hz, 2 ms stimulated ROS/RNS accumulation and Nrf2 activation. We also showed that expression of NQO1, HO-1 and GCLM increased after EPS-induced muscle contraction and was remarkably suppressed in cells with Nrf2 knockdown. We also found that the antioxidant N-acetylcysteine (NAC significantly attenuated Nrf2 activation after EPS, whereas the nitric oxide synthetase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME did not. Furthermore, Nrf2 knockdown after EPS markedly decreased ROS/RNS redox potential and cell viability and increased expression of the apoptosis marker Annexin V in C2C12 myotubes. These results indicate that Nrf2 activation and expression of Nrf2 regulated-genes protected muscle against the increased ROS caused by EPS-induced muscle contraction. Thus, our findings suggest that Nrf2 may be a key factor for preservation of muscle function during muscle contraction.

  17. Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity

    International Nuclear Information System (INIS)

    Wang Xiaojun; Sun Zheng; Chen Weimin; Eblin, Kylee E.; Gandolfi, Jay A.; Zhang, Donna D.

    2007-01-01

    Arsenic is widely spread in our living environment and imposes a big challenge on human health worldwide. Arsenic damages biological systems through multiple mechanisms including the generation of reactive oxygen species. The transcription factor Nrf2 regulates the cellular antioxidant response that protects cells from various insults. In this study, the protective role of Nrf2 in arsenic toxicity was investigated in a human bladder urothelial cell line, UROtsa. Using a UROtsa cell line stably infected with Nrf2-siRNA, we clearly demonstrate that compromised Nrf2 expression sensitized the cells to As(III)- and MMA(III)-induced toxicity. On the other hand, the activation of the Nrf2 pathway by tert-butylhydroquinone (tBHQ) and sulforaphane (SF), the known Nrf2-inducers, rendered UROtsa cells more resistant to As(III) and MMA(III). Furthermore, the wild-type mouse embryo fibroblast (WT-MEF) cells were protected from As(III)- and MMA(III)-induced toxicity following Nrf2 activation by tBHQ or SF, whereas neither tBHQ nor SF conferred protection in the Nrf2 -/- MEF cells, demonstrating that tBHQ- or SF-mediated protection against As(III)- and MMA(III)-induced toxicity depends on Nrf2 activation. These results, obtained by both loss of function and gain of function analyses, clearly demonstrate the protective role of Nrf2 in arsenic-induced toxicity. The current work lays the groundwork for using Nrf2 activators for therapeutic and dietary interventions against adverse effects of arsenic

  18. Conceptual Foundations Of Deliberative Democracy

    Directory of Open Access Journals (Sweden)

    Елизавета Васильевна Золотарева

    2013-12-01

    Full Text Available The article is dedicated to the analysis of theoretical foundations of deliberative model of democracy that is formed on the basis of synthesis of traditionally opposing approaches to research of democracy — liberal political philosophy (J. Rawls and critical social theory (J. Habermas. Special attention is paid to the problems of testing of normative requirements to the public discourse as the basis of deliberative process.

  19. Cognitive Foundations for Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Greitzer, Frank L.; Noonan, Christine F.; Franklin, Lyndsey

    2011-02-25

    In this report, we provide an overview of scientific/technical literature on information visualization and VA. Topics discussed include an update and overview of the extensive literature search conducted for this study, the nature and purpose of the field, major research thrusts, and scientific foundations. We review methodologies for evaluating and measuring the impact of VA technologies as well as taxonomies that have been proposed for various purposes to support the VA community. A cognitive science perspective underlies each of these discussions.

  20. Dihydro-CDDO-trifluoroethyl amide (dh404, a novel Nrf2 activator, suppresses oxidative stress in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Tomonaga Ichikawa

    Full Text Available Targeting Nrf2 signaling appears to be an attractive approach for the treatment of maladaptive cardiac remodeling and dysfunction; however, pharmacological modulation of the Nrf2 pathway in the cardiovascular system remains to be established. Herein, we report that a novel synthetic triterpenoid derivative, dihydro-CDDO-trifluoroethyl amide (dh404, activates Nrf2 and suppresses oxidative stress in cardiomyocytes. Dh404 interrupted the Keap1-Cul3-Rbx1 E3 ligase complex-mediated Nrf2 ubiquitination and subsequent degradation saturating the binding capacity of Keap1 to Nrf2, thereby rendering more Nrf2 to be translocated into the nuclei to activate Nrf2-driven gene transcription. A mutant Keap1 protein containing a single cysteine-to-serine substitution at residue 151 within the BTB domain of Keap1 was resistant to dh404-induced stabilization of Nrf2 protein. In addition, dh404 did not dissociate the interaction of Nrf2 with the Keap1-Cul3-Rbx1 E3 ligase complex. Thus, it is likely that dh404 inhibits the ability of Keap1-Cul3-Rbx1 E3 ligase complex to target Nrf2 for ubiquitination and degradation via modifying Cys-151 of Keap1 to change the conformation of the complex. Moreover, dh404 was able to stabilize Nrf2 protein, to enhance Nrf2 nuclear translocation, to activate Nrf2-driven transcription, and to suppress angiotensin II (Ang II-induced oxidative stress in cardiomyocytes. Knockdown of Nrf2 almost blocked the anti-oxidative effect of dh404. Dh404 activated Nrf2 signaling in the heart. Taken together, dh404 appears to be a novel Nrf2 activator with a therapeutic potential for cardiac diseases via suppressing oxidative stress.

  1. Pulmonary Fibrosis Foundation

    Science.gov (United States)

    ... submissions. MORE We Imagine a World Without Pulmonary Fibrosis The Pulmonary Fibrosis Foundation mobilizes people and resources to provide ... its battle against the deadly lung disease, pulmonary fibrosis (PF). PULMONARY FIBROSIS WALK SURPASSES PARTICIPATION AND FUNDRAISING GOALS Nearly ...

  2. Women's Heart Foundation

    Science.gov (United States)

    ... News Email: Click for e-News archive The Women's Heart Foundation is a 501c3 dedicated to prevention, ... Care Initiative® to achieve excellence of care of women. Executive nurses, civic leaders, women survivors and sponsors ...

  3. Pediatric Brain Tumor Foundation

    Science.gov (United States)

    ... navigate their brain tumor diagnosis. WATCH AND SHARE Brain tumors and their treatment can be deadly so ... Pediatric Central Nervous System Cancers Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  4. The foundations of statistics

    CERN Document Server

    Savage, Leonard J

    1972-01-01

    Classic analysis of the foundations of statistics and development of personal probability, one of the greatest controversies in modern statistical thought. Revised edition. Calculus, probability, statistics, and Boolean algebra are recommended.

  5. Hepatitis B Foundation

    Science.gov (United States)

    ... worldwide 2 Billion People have been infected with Hepatitis B Worldwide The Hepatitis B Foundation is working ... of people living with hepatitis B. Learn About Hepatitis B in 11 Other Languages . Resource Video See ...

  6. American Lyme Disease Foundation

    Science.gov (United States)

    ... Infectious Diseases, 35: 451-464, 2002) What is Lyme Disease? Lyme disease (LD) is an infection caused by ... mission with your own tax-deductible contribution. American Lyme Disease Foundation, Inc. PO Box 466 Lyme, CT 06371 ...

  7. Moebius Syndrome Foundation

    Science.gov (United States)

    ... craniofacial/neurological disorder. Individuals with Moebius syndrome cannot smile or frown, and do not have lateral eye ... the organization to ensure that they are in line with the mission of the Moebius Syndrome Foundation. ...

  8. National Headache Foundation

    Science.gov (United States)

    ... Headache Topic Sheets (Spanish) Headache FAQ NHF Webinars Education Modules MigrainePro™ Children’s Headache Disorders New Perspectives on Caffeine and Headache War Veterans Health Resource Initiative National Headache Foundation Brochures ...

  9. Foundations of laser spectroscopy

    CERN Document Server

    Stenholm, Stig

    2005-01-01

    A simple presentation of the theoretical foundations of steady-state laser spectroscopy, this text helps students to apply theory to calculations with a systematic series of examples and exercises. 1984 edition.

  10. Foundational aspects of security

    DEFF Research Database (Denmark)

    Chatzikokolakis, Konstantinos; Mödersheim, Sebastian Alexander; Palamidessi, Catuscia

    2014-01-01

    This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security.......This Special Issue of the Journal of Computer Security focuses on foundational aspects of security, which in recent years have helped change much of the way we think about and approach system security....

  11. Foundations of Neuromorphic Computing

    Science.gov (United States)

    2013-05-01

    paradigms: few sensors/complex computations and many sensors/simple computation. Challenges with Nano-enabled Neuromorphic Chips A wide variety of...FOUNDATIONS OF NEUROMORPHIC COMPUTING MAY 2013 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE; DISTRIBUTION...2009 – SEP 2012 4. TITLE AND SUBTITLE FOUNDATIONS OF NEUROMORPHIC COMPUTING 5a. CONTRACT NUMBER IN-HOUSE 5b. GRANT NUMBER N/A 5c. PROGRAM

  12. The dynamics of biomedical research organization in Brazil: the anatomy of a recent experience at the Oswaldo Cruz Foundation - DOI: 10.3395/reciis.v3i2.255en

    Directory of Open Access Journals (Sweden)

    Márcia de Oliveira Teixeira

    2009-06-01

    Full Text Available Biomedical research has undergone changes in the last four decades which have affected the design of new scientific approaches, the study of diseases associated with pathogenic microorganisms and the development of new products and industrial production processes. Additionally, they have affected new methodologies for preventing, treating and diagnosing transmissible and non-transmissible diseases, particularly the neglected ones. By identifying such elements, can we state that Brazil is witnessing the emergence of a new form of organizing the processes of research and production of technical-scientific knowledge in health? We attempt to answer this question through an analysis of the local dynamics in using organization and scientific research coordination tools in a centenarian institution with a strong tradition in biomedical research in Brazil, namely the Oswaldo Cruz Foundation. We start by providing an analytical description of the Foundation between 2001 and 2003. This description comprises three sections which cover: the organization and institutional goals; fields of research; management and assessment methods regarding scientific research and technological development at Fiocruz; means of funding and assessment methods and the configuration and dynamics of cooperative networks. We conclude by making some final comments of a general and specific nature. This aims to make a contribution in order to help perfect the local organization process of scientific research targeting technological advancement in the field of Brazilian public health in an institution which has been playing a central role in formulating, implementing and assessing health policies in the country.

  13. Nrf2 impacts cellular bioenergetics by controlling substrate availability for mitochondrial respiration

    Directory of Open Access Journals (Sweden)

    Kira M. Holmström

    2013-06-01

    Transcription factor Nrf2 and its repressor Keap1 regulate a network of cytoprotective genes involving more than 1% of the genome, their best known targets being drug-metabolizing and antioxidant genes. Here we demonstrate a novel role for this pathway in directly regulating mitochondrial bioenergetics in murine neurons and embryonic fibroblasts. Loss of Nrf2 leads to mitochondrial depolarisation, decreased ATP levels and impaired respiration, whereas genetic activation of Nrf2 increases the mitochondrial membrane potential and ATP levels, the rate of respiration and the efficiency of oxidative phosphorylation. We further show that Nrf2-deficient cells have increased production of ATP in glycolysis, which is then used by the F1Fo-ATPase for maintenance of the mitochondrial membrane potential. While the levels and in vitro activities of the respiratory complexes are unaffected by Nrf2 deletion, their activities in isolated mitochondria and intact live cells are substantially impaired. In addition, the rate of regeneration of NADH after inhibition of respiration is much slower in Nrf2-knockout cells than in their wild-type counterparts. Taken together, these results show that Nrf2 directly regulates cellular energy metabolism through modulating the availability of substrates for mitochondrial respiration. Our findings highlight the importance of efficient energy metabolism in Nrf2-mediated cytoprotection.

  14. Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yao Zhu

    2016-08-01

    Full Text Available Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL, one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2-regulated genes such as heme oxygenase-1 (HO-1 and NAD(PH dehydrogenase (quinone1 (NQO1. However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS and malondialdehyde (MDA, and improved the activities of superoxide dismutase (SOD and catalase (CAT, resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

  15. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases.

    Science.gov (United States)

    Kumar, Hemant; Kim, In-Su; More, Sandeep Vasant; Kim, Byung-Wook; Choi, Dong-Kug

    2014-01-01

    Covering: 2000 to 2013. Oxidative stress is the central component of chronic diseases. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway is vital in the up-regulation of cytoprotective genes and enzymes in response to oxidative stress and treatment with certain dietary phytochemicals. Herein, we classify bioactive compounds derived from natural products that are Nrf2/ARE pathway activators and recapitulate the molecular mechanisms for inducing Nrf2 to provide favorable effects in experimental models of chronic diseases. Moreover, pharmacological inhibition of Nrf2 signalling has emerged as promising strategy against multi-drug resistance thereby improving the treatment efficacy. We have also enlisted natural product-derived inhibitors of Nrf2/ARE pathway.

  16. When defense becomes dangerous – transcription factor Nrf2 and cancer

    Directory of Open Access Journals (Sweden)

    Adam Krysztofiak

    2015-01-01

    Full Text Available The transcription factor Nrf2 controls the expression of genes encoding cytoprotective enzymes and proteins. Its activation is related to conformational changes in the inhibitory protein Keap1 and/or Nrf2 phosphorylation by upstream kinases. Activation of Nrf2 can lead to the induction of phase II enzymes responsible for the inactivation of potential carcinogens. This may constitute an important strategy of chemoprevention. Moreover, these enzymatic systems participating in the biotransformation of drugs can reduce their therapeutic effects, contributing to drug resistance. For this reason, a clear understanding of the role of Nrf2 is essential to assess the beneficial and adverse effects of its up-regulation, particularly in relation to the prevention and treatment of cancer. This article summarizes the current state of knowledge on the significance of Nrf2 in tumorigenesis.

  17. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  18. 30 January 2012 - Danish National Research Foundation Chairman of board K. Bock and University of Copenhagen Rector R. Hemmingsen visiting ATLAS underground experimental area, CERN Control Centre and ALICE underground experimental area, throughout accompanied by J. Dines Hansen and B. Svane Nielsen; signing the guest book with CERN Director for Research and Scientific Computing S. Bertolucci and Head of International Relations F. Pauss.

    CERN Document Server

    Jean-Claude Gadmer

    2012-01-01

    30 January 2012 - Danish National Research Foundation Chairman of board K. Bock and University of Copenhagen Rector R. Hemmingsen visiting ATLAS underground experimental area, CERN Control Centre and ALICE underground experimental area, throughout accompanied by J. Dines Hansen and B. Svane Nielsen; signing the guest book with CERN Director for Research and Scientific Computing S. Bertolucci and Head of International Relations F. Pauss.

  19. The Nrf1 CNC-bZIP protein is regulated by the proteasome and activated by hypoxia.

    Science.gov (United States)

    Chepelev, Nikolai L; Bennitz, Joshua D; Huang, Ting; McBride, Skye; Willmore, William G

    2011-01-01

    Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is a transcription factor mediating cellular responses to xenobiotic and pro-oxidant stress. Nrf1 regulates the transcription of many stress-related genes through the electrophile response elements (EpREs) located in their promoter regions. Despite its potential importance in human health, the mechanisms controlling Nrf1 have not been addressed fully. We found that proteasomal inhibitors MG-132 and clasto-lactacystin-β-lactone stabilized the protein expression of full-length Nrf1 in both COS7 and WFF2002 cells. Concomitantly, proteasomal inhibition decreased the expression of a smaller, N-terminal Nrf1 fragment, with an approximate molecular weight of 23 kDa. The EpRE-luciferase reporter assays revealed that proteasomal inhibition markedly inhibited the Nrf1 transactivational activity. These results support earlier hypotheses that the 26 S proteasome processes Nrf1 into its active form by removing its inhibitory N-terminal domain anchoring Nrf1 to the endoplasmic reticulum. Immunoprecipitation demonstrated that Nrf1 is ubiquitinated and that proteasomal inhibition increased the degree of Nrf1 ubiquitination. Furthermore, Nrf1 protein had a half-life of approximately 5 hours in COS7 cells. In contrast, hypoxia (1% O(2)) significantly increased the luciferase reporter activity of exogenous Nrf1 protein, while decreasing the protein expression of p65, a shorter form of Nrf1, known to act as a repressor of EpRE-controlled gene expression. Finally, the protein phosphatase inhibitor okadaic acid activated Nrf1 reporter activity, while the latter was repressed by the PKC inhibitor staurosporine. Collectively, our data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing and proteasomal-mediated degradation as well as by its phosphorylation status. © 2011 Chepelev et al.

  20. The rise of antioxidant signaling-The evolution and hormetic actions of Nrf2

    International Nuclear Information System (INIS)

    Maher, Jonathan; Yamamoto, Masayuki

    2010-01-01

    Organisms have evolved sophisticated and redundant mechanisms to manage oxidative and electrophilic challenges that arise from internal metabolism or xenobiotic challenge for survival. NF-E2-related factor 2 (Nrf2) is a transcription factor that has evolved over millennia from primitive origins, with homologues traceable back to invertebrate Caenorhabditis and Drosophila species. The ancestry of Nrf2 clearly has deep-seated roots in hematopoiesis, yet has diversified into a transcription factor that can mediate a multitude of antioxidant signaling and detoxification genes. In higher organisms, a more sophisticated means of tightly regulating Nrf2 activity was introduced via the cysteine-rich kelch-like ECH-associated protein 1 (Keap1), thus suggesting a need to modulate Nrf2 activity. This is evidenced in Keap1 -/- mice, which succumb to juvenile mortality due to hyperkeratosis of the gastrointestinal tract. Although Nrf2 activation protects against acute toxicity and prevents or attenuates several disease states, constitutive activation in some tumors leads to poor clinical outcomes, suggesting Nrf2 has evolved in response to a multitude of selective pressures. The purpose of this review is to examine the origins of Nrf2, while highlighting the versatility and protective abilities elicited upon activation. Various model systems in which Nrf2 is normally beneficial but in which exaggerated pharmacology exacerbates a physiological or pathological condition will be addressed. Although Darwinian principles have selected Nrf2 activity for maximal beneficial effect based on environmental and oxidative challenge, both sub- or super-physiological effects have been noted to be detrimental. The functions of Nrf2 thus suggest a hormetic factor that has evolved empirically over time.

  1. Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling.

    Science.gov (United States)

    Dong, Wenwen; Yang, Bei; Wang, Linlin; Li, Bingxuan; Guo, Xiangshen; Zhang, Miao; Jiang, Zhenfei; Fu, Jingqi; Pi, Jingbo; Guan, Dawei; Zhao, Rui

    2018-05-01

    Traumatic brain injury (TBI), which leads to high mortality and morbidity, is a prominent public health problem worldwide with no effective treatment. Curcumin has been shown to be beneficial for neuroprotection in vivo and in vitro, but the underlying mechanism remains unclear. This study determined whether the neuroprotective role of curcumin in mouse TBI is dependent on the NF-E2-related factor (Nrf2) pathway. The Feeney weight-drop contusion model was used to mimic TBI. Curcumin was administered intraperitoneally 15 min after TBI induction, and brains were collected at 24 h after TBI. The levels of Nrf2 and its downstream genes (Hmox-1, Nqo1, Gclm, and Gclc) were detected by Western blot and qRT-PCR at 24 h after TBI. In addition, edema, oxidative damage, cell apoptosis and inflammatory reactions were evaluated in wild type (WT) and Nrf2-knockout (Nrf2-KO) mice to explore the role of Nrf2 signaling after curcumin treatment. In wild type mice, curcumin treatment resulted in reduced ipsilateral cortex injury, neutrophil infiltration, and microglia activation, improving neuron survival against TBI-induced apoptosis and degeneration. These effects were accompanied by increased expression and nuclear translocation of Nrf2, and enhanced expression of antioxidant enzymes. However, Nrf2 deletion attenuated the neuroprotective effects of curcumin in Nrf2-KO mice after TBI. These findings demonstrated that curcumin effects on TBI are associated with the activation the Nrf2 pathway, providing novel insights into the neuroprotective role of Nrf2 and the potential therapeutic use of curcumin for TBI. Copyright © 2018. Published by Elsevier Inc.

  2. Detection and widespread distribution of the nrfA gene encoding nitrite reduction to ammonia, a short circuit in the biological nitrogen cycle that competes with denitrification

    NARCIS (Netherlands)

    Mohan, S.B.; Schmid, M.C.; Jetten, M.S.M.; Cole, J.

    2004-01-01

    Degenerate primers to detect nrfA were designed by aligning six nrfA sequences including Escherichia coli K-12, Sufurospirillum deleyianum and Wolinella succinogenes. These primers amplified a 490 by fragment of nrfA. The ability of these primers to detect nrfA was tested with chromosomal DNA

  3. NRF2 ACTIVATION AS TARGET TO IMPLEMENT THERAPEUTIC TREATMENTS

    Directory of Open Access Journals (Sweden)

    Velio eBocci

    2015-02-01

    Full Text Available A chronic increase of oxidative stress is typical of serious pathologies such as myocardial infarction, stroke, chronic limb ischemia, chronic obstructive pulmonary disease (COPD, type II-diabetes, age-related macular degeneration leads to an epic increase of morbidity and mortality in all countries of the world. The initial inflammation followed by an excessive release of reactive oxygen species (ROS implies a diffused cellular injury that needs to be corrected by an inducible expression of the innate detoxifying and antioxidant system. The transcription factor Nrf2, when properly activated, is able to restore a redox homeostasis and possibly improve human health.

  4. Foundations of Risk Analysis

    CERN Document Server

    Aven, Terje

    2012-01-01

    Foundations of Risk Analysis presents the issues core to risk analysis - understanding what risk means, expressing risk, building risk models, addressing uncertainty, and applying probability models to real problems. The author provides the readers with the knowledge and basic thinking they require to successfully manage risk and uncertainty to support decision making. This updated edition reflects recent developments on risk and uncertainty concepts, representations and treatment. New material in Foundations of Risk Analysis includes:An up to date presentation of how to understand, define and

  5. Foundations of stochastic analysis

    CERN Document Server

    Rao, M M; Lukacs, E

    1981-01-01

    Foundations of Stochastic Analysis deals with the foundations of the theory of Kolmogorov and Bochner and its impact on the growth of stochastic analysis. Topics covered range from conditional expectations and probabilities to projective and direct limits, as well as martingales and likelihood ratios. Abstract martingales and their applications are also discussed. Comprised of five chapters, this volume begins with an overview of the basic Kolmogorov-Bochner theorem, followed by a discussion on conditional expectations and probabilities containing several characterizations of operators and mea

  6. Optimization Foundations and Applications

    CERN Document Server

    Miller, H Ronald

    2011-01-01

    A thorough and highly accessible resource for analysts in a broad range of social sciences. Optimization: Foundations and Applications presents a series of approaches to the challenges faced by analysts who must find the best way to accomplish particular objectives, usually with the added complication of constraints on the available choices. Award-winning educator Ronald E. Miller provides detailed coverage of both classical, calculus-based approaches and newer, computer-based iterative methods. Dr. Miller lays a solid foundation for both linear and nonlinear models and quickly moves on to dis

  7. Foundations of predictive analytics

    CERN Document Server

    Wu, James

    2012-01-01

    Drawing on the authors' two decades of experience in applied modeling and data mining, Foundations of Predictive Analytics presents the fundamental background required for analyzing data and building models for many practical applications, such as consumer behavior modeling, risk and marketing analytics, and other areas. It also discusses a variety of practical topics that are frequently missing from similar texts. The book begins with the statistical and linear algebra/matrix foundation of modeling methods, from distributions to cumulant and copula functions to Cornish--Fisher expansion and o

  8. Novel function of transcription factor Nrf2 as an inhibitor of RON tyrosine kinase receptor-mediated cancer cell invasion.

    Science.gov (United States)

    Thangasamy, Amalraj; Rogge, Jessica; Krishnegowda, Naveen K; Freeman, James W; Ammanamanchi, Sudhakar

    2011-09-16

    Recepteur d' origine nantais (RON), a tyrosine kinase receptor, is aberrantly expressed in human tumors and promotes cancer cell invasion. RON receptor activation is also associated with resistance to tamoxifen treatment in breast cancer cells. Nrf2 is a positive regulator of cytoprotective genes. Using chromatin immunoprecipitation (ChIP) and site-directed mutagenesis studies of the RON promoter, we identified Nrf2 as a negative regulator of RON gene expression. High Nrf2 and low RON expression was observed in normal mammary tissue whereas high RON and low or undetectable expression of Nrf2 was observed in breast tumors. The Nrf2 inducer sulforaphane (SFN) as well as ectopic Nrf2 expression or knock-down of the Nrf2 negative regulator keap1, which stabilizes Nrf2, inhibited RON expression and invasion of carcinoma cells. Consequently, our studies identified a novel functional role for Nrf2 as a "repressor" and RON kinase as a molecular target of SFN, which mediates the anti-tumor effects of SFN. These results are not limited to breast cancer cells since the Nrf2 inducer SFN stabilized Nrf2 and inhibited RON expression in carcinoma cells from various tumor types.

  9. Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity

    International Nuclear Information System (INIS)

    Okawa, Hiromi; Motohashi, Hozumi; Kobayashi, Akira; Aburatani, Hiroyuki; Kensler, Thomas W.; Yamamoto, Masayuki

    2006-01-01

    Nrf2 is a key regulator of many detoxifying enzyme genes, and cytoplasmic protein Keap1 represses the Nrf2 activity under quiescent conditions. Germ line deletion of the keap1 gene results in constitutive activation of Nrf2, but the pups unexpectedly died before weaning. To investigate how constitutive activation of Nrf2 influences the detoxification system in adult mice, we generated mice bearing a hepatocyte-specific disruption of the keap1 gene. Homozygous mice were viable and their livers displayed no apparent abnormalities, but nuclear accumulation of Nrf2 is elevated. Microarray analysis revealed that, while many detoxifying enzyme genes are highly expressed, some of the typical Nrf2-dependent genes are only marginally increased in the Keap1-deficient liver. The mutant mice were significantly more resistant to toxic doses of acetaminophen than control animals. These results demonstrate that chronic activation of Nrf2 confers animals with resistance to xenobiotics without affecting the morphological and physiological integrity of hepatocytes

  10. Establishment of a cohort for the long-term clinical follow-up with dose reconstruction under the joint medical research project conducted by Sasakawa Memorial Health Foundation (Japan) and the Research Institute of Radiation Hygiene (Russia)

    International Nuclear Information System (INIS)

    Konstantinov, Y.O.; Bruk, G.Y.; Ershov, E.B.

    2000-01-01

    The cohort of children in the western districts of the Bryansk Region of Russia exposed to radiation following the Chernobyl accident is described in this paper. The cohort was selected under the Joint Medical Research Project on Dosimetry Associated with the Chernobyl Accident conducted by Sasakawa Memorial Health Foundation (SMHF, Japan) and the Research Institute of Radiation Hygiene (RIRH, Russia). The subjects of the Research Project are those people residing in the most contaminated areas of Russia who was 0 to 10 years old at the time of exposure. At the moment the cohort comprises 1210 subjects, though this number may slightly decrease in course of a follow-up in view of migration of population. Most of cohort subjects were examined on their health status within the framework of the Chernobyl Sasakawa Health and Medical Cooperation Project (CSHMCP) from 1991-1996. In view of the main findings of studies in CSHMCP were thyroid abnormalities, selection of subjects was conducted on the basis of the credible estimates of thyroid dose. Preference for subjects to be included into the cohort was defined by the availability of health examination data from previous study (1991-1996) and individual dosimetry, environmental and social data that may prove useful for reconstruction of individual dose. The primary data analyzed for subjects selection are measurements of iodine-131 in the thyroid in May-June 1986, questionnaire data on individual food habits and early measurements of radiocesium in the body of subjects made by RIRH from May to September 1986. Plausible analytical models were applied to calculate thyroid dose from available data. Previously worked out methods of thyroid dose reconstruction using early measurement data of radiocesium content in the body and questionnaire data on individual consumption of locally produced milk were reevaluated. Basing on these analytical procedures, the individual thyroid dose was ascribed to each member of the cohort. The

  11. Impedance of Bucket Foundations

    DEFF Research Database (Denmark)

    Andersen, Lars; Ibsen, Lars Bo; Liingaard, Morten

    2008-01-01

    Modern offshore wind turbines are flexible structures with natural frequencies near the excitation frequencies related to wave and wind-induced loads. In order to obtain a reliable prediction of the structural response, the dynamic stiffness of the foundation must be evaluated accurately. This pa...

  12. BrightFocus Foundation

    Science.gov (United States)

    ... About BrightFocus Foundation Featured Content BrightFocus: Investing in Science to Save Mind and Sight We're here to help. Explore ... recognition is very important. Monday, November 6, 2017 New Diagnosis? Managing a mind and sight disease is a journey. And you’ ...

  13. Foundations of factor analysis

    CERN Document Server

    Mulaik, Stanley A

    2009-01-01

    Introduction Factor Analysis and Structural Theories Brief History of Factor Analysis as a Linear Model Example of Factor AnalysisMathematical Foundations for Factor Analysis Introduction Scalar AlgebraVectorsMatrix AlgebraDeterminants Treatment of Variables as Vectors Maxima and Minima of FunctionsComposite Variables and Linear Transformations Introduction Composite Variables Unweighted Composite VariablesDifferentially Weighted Composites Matrix EquationsMulti

  14. Buckling of Bucket Foundations

    DEFF Research Database (Denmark)

    Madsen, Søren; Andersen, Lars Vabbersgaard; Ibsen, Lars Bo

    2012-01-01

    In this paper, the risk of structural buckling during installation of large-diameter bucket foundations is addressed using numerical methods. Imperfect geometries are introduced based on the pre-buckling mode shapes from a linear Eigenvalue buckling analysis. Various imperfect geometries are intr...

  15. American Porphyria Foundation

    Science.gov (United States)

    ... Nicole Castelano Gregary Edwards Megan Parrish ~ How the dog I didn't want became the dog I'd always dreamed of Darnisha Davenport Liz ... or through the site for commercial or public purposes. The American Porphyria Foundation (APF) Tax Forms 990 ...

  16. Foundations of powder metallurgy

    International Nuclear Information System (INIS)

    Libenson, G.A.

    1987-01-01

    Consideration is being given to physicochemical foundations and technology of metal powders, moulding and sintering of bars, made of them or their mixtures with nonmetal powders. Data on he design of basic equipment used in the processes of powder metallurgy and its servicing are presented. General requirements of safety engineering when fabricating metal powders and products of them are mentioned

  17. Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice.

    Directory of Open Access Journals (Sweden)

    Thomas E Sussan

    Full Text Available BACKGROUND: Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf2(-/- causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis. PRINCIPAL FINDINGS: To investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf2(-/- mice with apoliporotein E-deficient (ApoE(-/- mice. ApoE(-/- and ApoE(-/-Nrf2(-/- mice were fed an atherogenic diet for 20 weeks, and plaque area was assessed in the aortas. Surprisingly, ApoE(-/-Nrf2(-/- mice exhibited significantly smaller plaque area than ApoE(-/- controls (11.5% vs 29.5%. This decrease in plaque area observed in ApoE(-/-Nrf2(-/- mice was associated with a significant decrease in uptake of modified low density lipoproteins (AcLDL by isolated macrophages from ApoE(-/-Nrf2(-/- mice. Furthermore, atherosclerotic plaques and isolated macrophages from ApoE(-/-Nrf2(-/- mice exhibited decreased expression of the scavenger receptor CD36. CONCLUSIONS: Nrf2 is pro-atherogenic in mice, despite its antioxidative function. The net pro-atherogenic effect of Nrf2 may be mediated via positive regulation of CD36. Our data demonstrates that the potential effects of Nrf2-targeted therapies on cardiovascular disease need to be investigated.

  18. Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2015-01-01

    Full Text Available Cardiovascular disease (CVD causes an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Oxidative stress plays a major role in the pathophysiology of cardiac disorders. Several studies have highlighted the cardinal role played by the overproduction of reactive oxygen or nitrogen species in the pathogenesis of ischemic myocardial damage and consequent cardiac dysfunction. Isothiocyanates (ITC are sulfur-containing compounds that are broadly distributed among cruciferous vegetables. Sulforaphane (SFN is an ITC shown to possess anticancer activities by both in vivo and epidemiological studies. Recent data have indicated that the beneficial effects of SFN in CVD are due to its antioxidant and anti-inflammatory properties. SFN activates NF-E2-related factor 2 (Nrf2, a basic leucine zipper transcription factor that serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than a hundred cytoprotective proteins, including antioxidants and phase II detoxifying enzymes. This review will summarize the evidence from clinical studies and animal experiments relating to the potential mechanisms by which SFN modulates Nrf2 activation and protects against CVD.

  19. Gap analysis: rethinking the conceptual foundations

    OpenAIRE

    Langford, Gary O.; Franck, Raymond; Huynh, Tom; Lewis, Ira A.

    2007-01-01

    Acquisition research (Graduate School of Business & Public Policy) Gap Analysis is widely regarded as a useful tool to facilitate commercial and defense system acquisitions. This paper is a rethinking of the theoretical foundations and systematics of Gap Analysis with practical extensions to illustrate its utility and limitations. It also provides a new perspective on those theoretical foundations from the perspectives of systems and value engineering. The growing sophistication and comple...

  20. CENTRIFUGAL VIBRATION TEST OF RC PILE FOUNDATION

    Science.gov (United States)

    Higuchi, Shunichi; Tsutsumiuchi, Takahiro; Otsuka, Rinna; Ito, Koji; Ejiri, Joji

    It is necessary that nonlinear responses of structures are clarified by soil-structure interaction analysis for the purpose of evaluating the seismic performances of underground structure or foundation structure. In this research, centrifuge shake table tests of reinforced concrete pile foundation installed in the liquefied ground were conducted. Then, finite element analyses for the tests were conducted to confirm an applicability of the analytical method by comparing the experimental results and analytical results.

  1. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis.

    Science.gov (United States)

    Widenmaier, Scott B; Snyder, Nicole A; Nguyen, Truc B; Arduini, Alessandro; Lee, Grace Y; Arruda, Ana Paula; Saksi, Jani; Bartelt, Alexander; Hotamisligil, Gökhan S

    2017-11-16

    Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity. In Nrf1 deficiency, in vivo cholesterol challenges induce massive hepatic cholesterol accumulation and damage, which is rescued by replacing Nrf1 exogenously. This Nrf1-mediated mechanism involves the suppression of CD36-driven inflammatory signaling and derepression of liver X receptor activity. These findings reveal Nrf1 as a guardian of cholesterol homeostasis and a core component of adaptive responses to excess cellular cholesterol. Copyright © 2017. Published by Elsevier Inc.

  2. Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2018-01-11

    Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

  3. Targeting of the Glutathione, Thioredoxin, and Nrf2 Antioxidant Systems in Head and Neck Cancer.

    Science.gov (United States)

    Roh, Jong-Lyel; Jang, Hyejin; Kim, Eun Hye; Shin, Daiha

    2017-07-10

    The glutathione (GSH), thioredoxin (Trx), and Nrf2 systems represent a major defense against reactive oxygen species (ROS), the cellular imbalance of which in cancer promotes growth and therapeutic resistance. This study investigated whether targeting the GSH, Trx, and Nrf2 antioxidant systems effectively eliminated head and neck cancer (HNC). At high concentrations, auranofin, but not buthionine sulfoximine (BSO) alone, decreased the viability of HNC, whereas even at low concentrations, auranofin plus BSO synergized to kill HNC cells. Dual silencing of the genes for GCLM and TrxR1 induced GSH depletion, Trx activity inhibition, and ROS accumulation, synergistically killing HNC cells. Inhibition of the GSH and Trx systems resulted in activation of the Nrf2-antioxidant response element (ARE) pathway, which may result in suboptimal GSH and Trx inhibition where HNC is resistant. Genetic inhibition of Nrf2 and/or HO-1 or trigonelline enhanced growth suppression, ROS accumulation, and cell death from GSH and Trx inhibition. The in vivo effects of GSH, Trx, and Nrf2 system inhibition were confirmed in a mouse HNC xenograft model by achieving growth inhibition >60% compared with those of control. Innovations: This study is the first to show that triple inhibition of GSH, Trx, and Nrf2 pathways could be an effective method to overcome the resistance of HNC. Inhibition of the Nrf2-ARE pathway in addition to dual inhibition of the GSH and Trx antioxidant systems can effectively eliminate resistant HNC. Antioxid. Redox Signal. 27, 106-114.

  4. Soybean-Derived Phytoalexins Improve Cognitive Function through Activation of Nrf2/HO-1 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ji Yeon Seo

    2018-01-01

    Full Text Available As soy-derived glyceollins are known to induce antioxidant enzymes in various types of cells and tissues, we hypothesized that the compounds could protect neurons from damage due to reactive oxygen species (ROS. In order to examine the neuroprotective effect of glyceollins, primary cortical neurons collected from mice and mouse hippocampal HT22 cells were challenged with glutamate. Glyceollins attenuated glutamate-induced cytotoxicity in primary cortical neuron isolated from mice carrying wild-type nuclear factor (erythroid-derived 2-like 2 (Nrf2, but the compounds were ineffective in those isolated from Nrf2 knockout mice, suggesting the involvement of the Nrf2 signaling pathway in glyceollin-mediated neuroprotection. Furthermore, the inhibition of heme oxygenase-1 (HO-1, a major downstream enzyme of Nrf2, abolished the suppressive effect of glyceollins against glutamate-induced ROS production and cytotoxicity, confirming that activation of HO-1 by glyceollins is responsible for the neuroprotection. To examine whether glyceollins also improve cognitive ability, mice pretreated with glyceollins were challenged with scopolamine and subjected to behavioral tests. Glyceollins attenuated scopolamine-induced cognitive impairment of mice, but failed to enhance memory in Nrf2 knockout mice, suggesting that the memory-enhancing effect is also mediated by the Nrf2 signaling pathway. Overall, glyceollins showed neuroprotection against glutamate-induced damage, and attenuated scopolamine-induced memory deficits in an Nrf2-dependent manner.

  5. Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins

    Directory of Open Access Journals (Sweden)

    Kirtikar Shukla

    2017-01-01

    Full Text Available We have shown earlier that pretreatment of cultured cells with aldose reductase (AR inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory responses. However, the effects of AR inhibitors on Nrf2-mediated anti-inflammatory responses have not been elucidated yet. We have investigated how AR inhibitor fidarestat protects high glucose- (HG- induced cell viability changes by increasing the expression of Nrf2 and its dependent phase II antioxidant enzymes. Fidarestat pretreatment prevents HG (25 mM-induced Thp1 monocyte viability. Further, treatment of Thp1 monocytes with fidarestat caused a time-dependent increase in the expression as well as the DNA-binding activity of Nrf2. In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase-1 (HO1 and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and kidney tissues. Further, AR inhibition increased the HG-induced expression of antioxidant enzymes such as SOD and catalase and activation of AMPK-α1 in Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent antioxidative proteins.

  6. Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins.

    Science.gov (United States)

    Shukla, Kirtikar; Pal, Pabitra Bikash; Sonowal, Himangshu; Srivastava, Satish K; Ramana, Kota V

    2017-01-01

    We have shown earlier that pretreatment of cultured cells with aldose reductase (AR) inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory responses. However, the effects of AR inhibitors on Nrf2-mediated anti-inflammatory responses have not been elucidated yet. We have investigated how AR inhibitor fidarestat protects high glucose- (HG-) induced cell viability changes by increasing the expression of Nrf2 and its dependent phase II antioxidant enzymes. Fidarestat pretreatment prevents HG (25 mM)-induced Thp1 monocyte viability. Further, treatment of Thp1 monocytes with fidarestat caused a time-dependent increase in the expression as well as the DNA-binding activity of Nrf2. In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase-1 (HO1) and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and kidney tissues. Further, AR inhibition increased the HG-induced expression of antioxidant enzymes such as SOD and catalase and activation of AMPK- α 1 in Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent antioxidative proteins.

  7. Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.

    Science.gov (United States)

    Deck, Lorraine M; Hunsaker, Lucy A; Vander Jagt, Thomas A; Whalen, Lisa J; Royer, Robert E; Vander Jagt, David L

    2018-01-01

    Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC 50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. Copyright © 2017. Published by Elsevier Masson SAS.

  8. Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis

    Directory of Open Access Journals (Sweden)

    Lidia Ibáñez

    2014-01-01

    Full Text Available Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2, an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis. Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−. Bone microarchitecture was analyzed by μCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123. Results. Sham-operated or ovariectomized Nrf2−/− mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/− mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro. Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

  9. NEWS: Solid foundations?

    Science.gov (United States)

    2000-07-01

    Among the initiatives to be found at UK universities is a vocational award with the title `University Foundation Degree' at Nottingham Trent University. This qualification will be offered in 14 different subjects including four in the Faculty of Science and Mathematics, in the areas of applied biology, applied sciences, chemistry and physics. The courses will be available on a two-year full-time, three-year sandwich or a part-time basis. Set at a higher standard and specification than the Higher National Diplomas which it replaces, the UFD has been devised in consultation with industry and will cover the technical and specialist areas demanded by employers to combat skills shortages. The UFD in applied sciences concentrates on practical applications through laboratory, IT and project work, supported by lectures and seminars. At the end students can enter the employment market or transfer onto the second year of a degree course. Science-based careers including research and development would be the aim of those taking the UFD in physics. The first year develops the fundamentals of modern physics supported by studies in mathematics, IT and computer programming, whilst year 2 is vocational in nature with industrial problem solving and work experience as well as an academic theme associated with environmental aspects of the subject. Those who complete the UFD will be allowed automatic progression to a specified honours degree course and would normally be expected to study for a further two years for this award. However, those demonstrating an outstanding academic performance can transfer to the linked degree programme at the end of the first year via fast-track modules. Back in May the UK's Quality Assurance Agency (QAA) announced new standard benchmarks for degrees. These will be introduced into higher education institutions from 2002 to outline the knowledge, understanding and skills a student should gain from a particular higher education course. These benchmark

  10. Real-Life Solutions to Real-Life Problems: Collaborating with a Non-Profit Foundation to Engage Honors Students in Applied Research

    Science.gov (United States)

    Stark, Emily

    2013-01-01

    Colleges and universities have long emphasized undergraduate research experiences as valuable activities for students. Collegiate honors programs in particular have embraced the role of student research as an integral experience for high-ability students, leading the way in developing the thesis-based model of undergraduate research that is…

  11. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jae Yun [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Cho, Seung Sik [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Da Eon [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Bang, Joon Seok [Graduate School of Clinical Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Jung, Young Suk [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  12. Constitutive activation of Nrf2 induces a stable reductive state in the mouse myocardium

    Directory of Open Access Journals (Sweden)

    Gobinath Shanmugam

    2017-08-01

    Full Text Available Redox homeostasis regulates key cellular signaling pathways in both physiology and pathology. The cell's antioxidant response provides a defense against oxidative stress and establishes a redox tone permissive for cell signaling. The molecular regulation of the well-known Keap1/Nrf2 system acts as sensor responding to changes in redox homeostasis and is poorly studied in the heart. Importantly, it is not yet known whether Nrf2 alone can serve as a master regulator of cellular redox homeostasis without compensation of the transcriptional regulation of antioxidant response element (ARE genes through alternate mechanisms. Here, we addressed this question using cardiac-specific transgenic expression at two different levels of constitutively active nuclear erythroid related factor 2 (caNrf2 functioning independently of Keap1. The caNrf2 mice showed augmentation of glutathione (GSH, the key regulator of the cellular thiol redox state. The Trans-AM assay for Nrf2-binding to the antioxidant response element (ARE showed a dose-dependent increase associated with upregulation of several major antioxidant genes and proteins. This was accompanied by a significant decrease in dihydroethidium staining and malondialdehyde (MDA in the caNrf2-TG mice myocardium. Interestingly, caNrf2 gene-dosage dependent redox changes were noted resulting in generation of a multi-stage model of pro-reductive and reductive conditions in the myocardium of TG-low and TG-high mice, respectively. These data clearly show that Nrf2 levels alone are capable of serving as the master regulator of the ARE. These models provide an important platform to investigate the impact of the Nrf2 system independent of the need to regulate the activity of Keap1 and the consequent exposure to pro-oxidants or electrophiles, which have numerous off-target effects.

  13. MDM2 controls NRF2 antioxidant activity in prevention of diabetic kidney disease.

    Science.gov (United States)

    Guo, Weiying; Tian, Dan; Jia, Ye; Huang, Wenlin; Jiang, Mengnan; Wang, Junnan; Sun, Weixia; Wu, Hao

    2018-04-26

    Oxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hypothesized that MDM2 enhances NRF2 antioxidant signaling in DKD given that MDM2 is a key negative regulator of P53. The MDM2 inhibitor nutlin3a elevated renal P53, inhibited NRF2 signaling and induced oxidative stress, inflammation, fibrosis, DKD-like renal pathology and albuminuria in the wild-type (WT) non-diabetic mice. These effects exhibited more prominently in nutlin3a-treated WT diabetic mice. Interestingly, nutlin3a failed to induce greater renal injuries in the Nrf2 knockout (KO) mice under both the diabetic and non-diabetic conditions, indicating that NRF2 predominantly mediates MDM2's action. On the contrary, P53 inhibition by pifithrin-α activated renal NRF2 signaling and the expression of Mdm2, and attenuated DKD in the WT diabetic mice, but not in the Nrf2 KO diabetic mice. In high glucose-treated mouse mesangial cells, P53 gene silencing completely abolished nutlin3a's inhibitory effect on NRF2 signaling. The present study demonstrates for the first time that MDM2 controls renal NRF2 antioxidant activity in DKD via inhibition of P53, providing MDM2 activation and P53 inhibition as novel strategies in the management of DKD. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Activation of Nrf2-mediated oxidative stress response in macrophages by hypochlorous acid

    International Nuclear Information System (INIS)

    Pi Jingbo; Zhang Qiang; Woods, Courtney G.; Wong, Victoria; Collins, Sheila; Andersen, Melvin E.

    2008-01-01

    Hypochlorous acid (HOCl), a potent oxidant generated when chlorine gas reacts with water, is important in the pathogenesis of many disorders. Transcription factor Nrf2-mediated antioxidant response represents a critical cellular defense mechanism that serves to maintain intracellular redox homeostasis and limit oxidative damage. In the present study, the effect of HOCl on Nrf2 activation was investigated in macrophages, one of the target cells of chlorine gas exposure. Exposure of RAW 264.7 macrophages to HOCl resulted in increased protein levels of Nrf2 in nuclear extractions, as well as a time- and dose-dependent increase in the expression of Nrf2 target genes, including heme oxygenase-1, NAD(P)H:quinone oxidoreductase 1 (NQO-1), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GS). Additionally, intracellular glutathione (GSH), which is the prime scavenger for HOCl in cells, decreased within the first hour of HOCl exposure. The decline was followed by a GSH rebound that surpassed the initial basal levels by up to 4-fold. This reversal in GSH levels closely correlated with the gene expression profile of GCLC and GS. To study the mechanisms of Nrf2 activation in response to HOCl exposure, we examined the effects of several antioxidants on Nrf2-mediated response. Pretreatment with cell-permeable catalase, N-acetyl-L-cysteine or GSH-monoethyl ester markedly reduced expression of NQO-1 and GCLC under HOCl challenge conditions, suggesting intracellular ROS-scavenging capacity affects HOCl-induced Nrf2 activation. Importantly, pre-activation of Nrf2 with low concentrations of pro-oxidants protected the cells against HOCl-induced cell damage. Taken together, we provide direct evidence that HOCl activates Nrf2-mediated antioxidant response, which protects cells from oxidative damage

  15. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    International Nuclear Information System (INIS)

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-01-01

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  16. Nrf2 mediates redox adaptation in NOX4-overexpressed non-small cell lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Qipeng; Yao, Bei; Li, Ning; Ma, Lei; Deng, Yanchao; Yang, Yang; Zeng, Cheng; Yang, Zhicheng [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Liu, Bing, E-mail: liubing520@gdpu.edu.cn [Department of Clinical Pharmacy, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 (China); Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou 510006 (China)

    2017-03-15

    The redox adaptation mechanisms in cancer cells are very complex and remain largely unclear. Our previous studies have confirmed that NADPH oxidase 4 (NOX4) is abundantly expressed in non-small cell lung cancer (NSCLC) and confers apoptosis resistance on NSCLC cells. However, the comprehensive mechanisms for NOX4-mediated oxidative resistance of cancer cells remain still undentified. The present study found that NOX4-derived H{sub 2}O{sub 2} enhanced the nuclear factor erythroid 2-related factor 2 (Nrf2) stability via disruption of redox-dependent proteasomal degradation and stimulated its activity through activation of PI3K signaling. Specifically, the results showed that ectopic NOX4 expression did not induce apoptosis of A549 cells; however, inhibition of Nrf2 resulted in obvious apoptotic death of NOX4-overexpressed A549 cells, accompanied by a significant increase in H{sub 2}O{sub 2} level and decrease in GSH content. Besides, inhibition of Nrf2 could suppress cell growth and efficiently reverse the enhancement effect of NOX4 on cell growth. The in vivo data confirmed that inhibition of Nrf2 could interfere apoptosis resistance in NOX4-overexpressed A549 tumors and led to cell growth inhibition. In conclusion, these results reveal that Nrf2 is critically involved in redox adaptation regulation in NOX4-overexpressed NSCLC cells. Therefore, NOX4 and Nrf2 may be promising combination targets against malignant progression of NSCLC. - Highlights: • NOX4-derived H{sub 2}O{sub 2} upregulates Nrf2 expression and activity in NSCLC. • Nrf2 confers apoptosis resistance in NOX4-overexpressed NSCLC cells. • Inhibition of Nrf2 reverses the enhancement effect of NOX4 on cell growth.

  17. Britanin Ameliorates Cerebral Ischemia-Reperfusion Injury by Inducing the Nrf2 Protective Pathway.

    Science.gov (United States)

    Wu, Guozhen; Zhu, Lili; Yuan, Xing; Chen, Hao; Xiong, Rui; Zhang, Shoude; Cheng, Hao; Shen, Yunheng; An, Huazhang; Li, Tiejun; Li, Honglin; Zhang, Weidong

    2017-10-10

    Oxidative stress is considered the major cause of tissue injury after cerebral ischemia. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is one of the most important defensive mechanisms against oxidative stresses and has been confirmed as a target for stroke treatment. Thus, we desired to find new Nrf2 activators and test their neuronal protective activity both in vivo and in vitro. The herb-derived compound, Britanin, is a potent inducer of the Nrf2 system. Britanin can induce the expression of protective enzymes and reverse oxygen-glucose deprivation, followed by reperfusion (OGD-R)-induced neuronal injury in primary cortical neurons in vitro. Furthermore, the administration of Britanin significantly ameliorated middle cerebral artery occlusion-reperfusion (MCAO-R) insult in vivo. We report here the crystal structure of the complex of Britanin and the BTB domain of Keap1. Britanin selectively binds to a conserved cysteine residue, cysteine 151, of Keap1 and inhibits Keap1-mediated ubiquitination of Nrf2, leading to induction of the Nrf2 pathway. Britanin is a potent inducer of Nrf2. The complex crystal structure of Britanin and the BTB domain of Keap1 help clarify the mechanism of Nrf2 induction. Britanin was proven to protect primary cortical neurons against OGD-R-induced injury in an Nrf2-dependant way. Additionally, Britanin had excellent cerebroprotective effect in an MCAO-R model. Our results demonstrate that the natural product Britanin with potent Nrf2-activating and neural protective activities both in vitro and in vivo could be developed into a cerebroprotective therapeutic agent. Antioxid. Redox Signal. 27, 754-768.

  18. ABCF2, an Nrf2 target gene, contributes to cisplatin resistance in ovarian cancer cells.

    Science.gov (United States)

    Bao, Lingjie; Wu, Jianfa; Dodson, Matthew; Rojo de la Vega, Elisa Montserrat; Ning, Yan; Zhang, Zhenbo; Yao, Ming; Zhang, Donna D; Xu, Congjian; Yi, Xiaofang

    2017-06-01

    Previously, we have demonstrated that NRF2 plays a key role in mediating cisplatin resistance in ovarian cancer. To further explore the mechanism underlying NRF2-dependent cisplatin resistance, we stably overexpressed or knocked down NRF2 in parental and cisplatin-resistant human ovarian cancer cells, respectively. These two pairs of stable cell lines were then subjected to microarray analysis, where we identified 18 putative NRF2 target genes. Among these genes, ABCF2, a cytosolic member of the ABC superfamily of transporters, has previously been reported to contribute to chemoresistance in clear cell ovarian cancer. A detailed analysis on ABCF2 revealed a functional antioxidant response element (ARE) in its promoter region, establishing ABCF2 as an NRF2 target gene. Next, we investigated the contribution of ABCF2 in NRF2-mediated cisplatin resistance using our stable ovarian cancer cell lines. The NRF2-overexpressing cell line, containing high levels of ABCF2, was more resistant to cisplatin-induced apoptosis compared to its control cell line; whereas the NRF2 knockdown cell line with low levels of ABCF2, was more sensitive to cisplatin treatment than its control cell line. Furthermore, transient overexpression of ABCF2 in the parental cells decreased apoptosis and increased cell viability following cisplatin treatment. Conversely, knockdown of ABCF2 using specific siRNA notably increased apoptosis and decreased cell viability in cisplatin-resistant cells treated with cisplatin. This data indicate that the novel NRF2 target gene, ABCF2, plays a critical role in cisplatin resistance in ovarian cancer, and that targeting ABCF2 may be a new strategy to improve chemotherapeutic efficiency. © 2017 Wiley Periodicals, Inc.

  19. Nrf2 is required to maintain the self-renewal of glioma stem cells

    International Nuclear Information System (INIS)

    Zhu, Jianhong; Wang, Handong; Sun, Qing; Ji, Xiangjun; Zhu, Lin; Cong, Zixiang; Zhou, Yuan; Liu, Huandong; Zhou, Mengliang

    2013-01-01

    Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioma stem cells (GSCs). Self-renewal is a complex biological process necessary for maintaining the glioma stem cells. Nuclear factor rythroid 2-related factor 2(Nrf2) plays a significant role in protecting cells from endogenous and exogenous stresses. Nrf2 is a key nuclear transcription factor that regulates antioxidant response element (ARE)-containing genes. Previous studies have demonstrated the significant role of Nrf2 in the proliferation of glioblastoma, and in their resistance to radioactive therapies. We examined the effect of knocking down Nrf2 in GSCs. Nrf2 expression was down-regulated by shRNA transinfected with lentivirus. Expression levels of Nestin, Nrf2, BMI-1, Sox2 and Cyclin E were assessed by western blotting, quantitative polymerase chain reaction (qPCR) and immunohistochemistry analysis. The capacity for self-renewal in vitro was assessed by genesis of colonies. The capacity for self-renewal in vivo was analyzed by tumor genesis of xenografts in nude mice. Knockdown of Nrf2 inhibited the proliferation of GSCs, and significantly reduced the expression of BMI-1, Sox2 and CyclinE. Knocking down of Nrf2 changed the cell cycle distribution of GSCs by causing an uncharacteristic increase in the proportion of cells in the G2 phase and a decrease in the proportion of cells in the S phase of the cell cycle. Nrf2 is required to maintain the self-renewal of GSCs, and its down-regulation can attenuate the self-renewal of GSCs significantly

  20. Can risk assessment predict suicide in secondary mental healthcare? Findings from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register.

    Science.gov (United States)

    Lopez-Morinigo, Javier-David; Fernandes, Andrea C; Shetty, Hitesh; Ayesa-Arriola, Rosa; Bari, Ashraful; Stewart, Robert; Dutta, Rina

    2018-06-02

    The predictive value of suicide risk assessment in secondary mental healthcare remains unclear. This study aimed to investigate the extent to which clinical risk assessment ratings can predict suicide among people receiving secondary mental healthcare. Retrospective inception cohort study (n = 13,758) from the South London and Maudsley NHS Foundation Trust (SLaM) (London, UK) linked with national mortality data (n = 81 suicides). Cox regression models assessed survival from the last suicide risk assessment and ROC curves evaluated the performance of risk assessment total scores. Hopelessness (RR = 2.24, 95% CI 1.05-4.80, p = 0.037) and having a significant loss (RR = 1.91, 95% CI 1.03-3.55, p = 0.041) were significantly associated with suicide in the multivariable Cox regression models. However, screening statistics for the best cut-off point (4-5) of the risk assessment total score were: sensitivity 0.65 (95% CI 0.54-0.76), specificity 0.62 (95% CI 0.62-0.63), positive predictive value 0.01 (95% CI 0.01-0.01) and negative predictive value 0.99 (95% CI 0.99-1.00). Although suicide was linked with hopelessness and having a significant loss, risk assessment performed poorly to predict such an uncommon outcome in a large case register of patients receiving secondary mental healthcare.

  1. Foundations of compositional model theory

    Czech Academy of Sciences Publication Activity Database

    Jiroušek, Radim

    2011-01-01

    Roč. 40, č. 6 (2011), s. 623-678 ISSN 0308-1079 R&D Projects: GA MŠk 1M0572; GA ČR GA201/09/1891; GA ČR GEICC/08/E010 Institutional research plan: CEZ:AV0Z10750506 Keywords : multidimensional probability distribution * conditional independence * graphical Markov model * composition of distributions Subject RIV: IN - Informatics, Computer Science Impact factor: 0.667, year: 2011 http://library.utia.cas.cz/separaty/2011/MTR/jirousek-foundations of compositional model theory.pdf

  2. Epigenetics Reactivation of Nrf2 in Prostate TRAMP C1 Cells by Curcumin Analogue FN1.

    Science.gov (United States)

    Li, Wenji; Pung, Doug; Su, Zheng-Yuan; Guo, Yue; Zhang, Chengyue; Yang, Anne Yuqing; Zheng, Xi; Du, Zhi-Yun; Zhang, Kun; Kong, Ah-Ng

    2016-04-18

    It has previously been shown that curcumin can effectively inhibit prostate cancer proliferation and progression in TRAMP mice, potentially acting through the hypomethylation of the Nrf2 gene promoter and hence activation of the Nrf2 pathway to enhance cell antioxidative defense. FN1 is a synthetic curcumin analogue that shows stronger anticancer activity than curcumin in other reports. We aimed to explore the epigenetic modification of FN1 that restores Nrf2 expression in TRAMP-C1 cells. Stably transfected HepG2-C8 cells were used to investigate the effect of FN1 on the Nrf2- antioxidant response element (ARE) pathway. Real-time quantitative PCR and Western blotting were applied to study the influence of FN1 on endogenous Nrf2 and its downstream genes. Bisulfite genomic sequencing (BGS) and methylated DNA immunoprecipitation (MeDIP) were then performed to examine the methylation profile of the Nrf2 promoter. An anchorage-independent colony-formation analysis was conducted to examine the tumor inhibition activity of FN1. Epigenetic modification enzymes, including DNMTs and HDACs, were investigated by Western blotting. The luciferase reporter assay indicated that FN1 was more potent than curcumin in activating the Nrf2-ARE pathway. FN1 increased the expression of Nrf2 and its downstream detoxifying enzymes. FN1 significantly inhibited the colony formation of TRAMP-C1 cells. BGS and MeDIP assays revealed that FN1 treatment (250 nM for 3 days) reduced the percentage of CpG methylation of the Nrf2 promoter. FN1 also downregulated epigenetic modification enzymes. In conclusion, our results suggest that FN1 is a novel anticancer agent for prostate cancer. In the TRAMP-C1 cell line, FN1 can increase the level of Nrf2 and downstream genes via activating the Nrf2-ARE pathway and inhibit the colony formation potentially through the decreased expression of keap1 coupled with CpG demethylation of the Nrf2 promoter. This CpG demethylation effect may come from decreased

  3. [History of the development of radiodiagnosis at the Russian Research Center of Roentgenology and Radiology: on the occasion of the 90th anniversary of its foundation].

    Science.gov (United States)

    Solodkiĭ, V A; Kotliarov, P M; Nudnov, N V

    2014-01-01

    The paper describes the history of the Russian Research Center of Roentgenology and Radiology set up 90 years ago, the main advances of the researchers of the Institute in roentgenology and radiodiagnosis in historical perspective--from the last century up to the present day. It gives a brief list of the most important procedures and publications on radiodiagnosis, which have been developed and published by the Institute's researchers.

  4. Cyber warfare building the scientific foundation

    CERN Document Server

    Jajodia, Sushil; Subrahmanian, VS; Swarup, Vipin; Wang, Cliff

    2015-01-01

    This book features a wide spectrum of the latest computer science research relating to cyber warfare, including military and policy dimensions. It is the first book to explore the scientific foundation of cyber warfare and features research from the areas of artificial intelligence, game theory, programming languages, graph theory and more. The high-level approach and emphasis on scientific rigor provides insights on ways to improve cyber warfare defense worldwide. Cyber Warfare: Building the Scientific Foundation targets researchers and practitioners working in cyber security, especially gove

  5. Antithetic Foundations of Economics

    OpenAIRE

    Marin DINU

    2011-01-01

    This paper aims at decrypting the manner in which the foundations of Economics as a science and the meanings of the relevant explanatory formulas are being shaped. My analytical endeavor focuses on understanding the peculiarities of what is referred to as the object of study of the science known as Economics, an academic synthesis of concept-related breakthroughs regarding economicity. The explicit purpose of this analysis is to identify perennial benchmarks in economic c...

  6. Topological Foundations of Electromagnetism

    CERN Document Server

    Barrett, Terrence W

    2008-01-01

    Topological Foundations of Electromagnetism seeks a fundamental understanding of the dynamics of electromagnetism; and marshals the evidence that in certain precisely defined topological conditions, electromagnetic theory (Maxwell's theory) must be extended or generalized in order to provide an explanation and understanding of, until now, unusual electromagnetic phenomena. Key to this generalization is an understanding of the circumstances under which the so-called A potential fields have physical effects. Basic to the approach taken is that the topological composition of electromagnetic field

  7. Foundations of image science

    CERN Document Server

    Barrett, Harrison H

    2013-01-01

    Winner of the 2006 Joseph W. Goodman Book Writing Award! A comprehensive treatment of the principles, mathematics, and statistics of image science In today's visually oriented society, images play an important role in conveying messages. From seismic imaging to satellite images to medical images, our modern society would be lost without images to enhance our understanding of our health, our culture, and our world. Foundations of Image Science presents a comprehensive treatment of the principles, mathematics, and st

  8. Foundations for Moral Relativism

    OpenAIRE

    Velleman, J. David

    2015-01-01

    In this new edition of Foundations for Moral Relativism, a distinguished moral philosopher tames a bugbear of current debate about cultural difference. J. David Velleman shows that different communities can indeed be subject to incompatible moralities, because their local mores are rationally binding. At the same time, he explains why the mores of different communities, even when incompatible, are still variations on the same moral themes. The book thus maps out a universe of many moral world...

  9. Wronski's Foundations of Mathematics.

    Science.gov (United States)

    Wagner, Roi

    2016-09-01

    Argument This paper reconstructs Wronski's philosophical foundations of mathematics. It uses his critique of Lagrange's algebraic analysis as a vignette to introduce the problems that he raised, and argues that these problems have not been properly appreciated by his contemporaries and subsequent commentators. The paper goes on to reconstruct Wronski's mathematical law of creation and his notions of theory and techne, in order to put his objections to Lagrange in their philosophical context. Finally, Wronski's proof of his universal law (the expansion of a given function by any series of functions) is reviewed in terms of the above reconstruction. I argue that Wronski's philosophical approach poses an alternative to the views of his contemporary mainstream mathematicians, which brings up the contingency of their choices, and bridges the foundational concerns of early modernity with those of the twentieth-century foundations crisis. I also argue that Wronski's views may be useful to contemporary philosophy of mathematical practice, if they are read against their metaphysical grain.

  10. Piper betle induces phase I & II genes through Nrf2/ARE signaling pathway in mouse embryonic fibroblasts derived from wild type and Nrf2 knockout cells.

    Science.gov (United States)

    Wan Hasan, Wan Nuraini; Kwak, Mi-Kyoung; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

    2014-02-23

    Nuclear factor-erythroid 2 p45 related factor 2 (Nrf2) is a primary transcription factor, protecting cells from oxidative stress by regulating a number of antioxidants and phase II detoxifying enzymes. Dietary components such as sulforaphane in broccoli and quercetin in onions have been shown to be inducers of Nrf2. Piper betle (PB) grows well in tropical climate and the leaves are used in a number of traditional remedies for the treatment of stomach ailments and infections among Asians. The aim of this study was to elucidate the effect of Piper betle (PB) leaves extract in Nrf2 signaling pathway by using 2 types of cells; mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) and Nrf2 knockout (N0) mice. WT and N0 cells were treated with 5 and 10 μg/ml of PB for 10 and 12-h for the determination of nuclear translocation of Nrf2 protein. Luciferase reporter gene activity was performed to evaluate the antioxidant response element (ARE)-induction by PB. Real-time PCR and Western blot were conducted on both WT and N0 cells after PB treatment for the determination of antioxidant enzymes [superoxide dismutase (SOD1) and heme-oxygenase (HO-1)], phase I oxidoreductase enzymes [ quinone oxidoreductase (NQO1)] and phase II detoxifying enzyme [glutathione S-transferase (GST)]. Nuclear translocation of Nrf2 by PB in WT cells was better after 10 h incubation compared to 12 h. Real time PCR and Western blot analysis showed increased expressions of Nrf2, NQO1 and GSTA1 genes with corresponding increases in glutathione, NQO1 and HO-1 proteins in WT cells. Reporter gene ARE was stimulated by PB as shown by ARE/luciferase assay. Interestingly, PB induced SOD1 gene and protein expressions in N0 cells but not in WT cells. The results of this study confirmed that PB activated Nrf2-ARE signaling pathway which subsequently induced some phase I oxidoreductase, phase II detoxifying and antioxidant genes expression via ARE reporter gene involved in the Nrf2 pathway with the

  11. Systemic administration of the apocarotenoid bixin protects skin against solar UV-induced damage through activation of NRF2.

    Science.gov (United States)

    Tao, Shasha; Park, Sophia L; Rojo de la Vega, Montserrat; Zhang, Donna D; Wondrak, Georg T

    2015-12-01

    Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photodamage and carcinogenesis, and an urgent need exists for improved molecular photoprotective strategies different from (or synergistic with) photon absorption. Recent studies suggest a photoprotective role of cutaneous gene expression orchestrated by the transcription factor NRF2 (nuclear factor-E2-related factor 2). Here we have explored the molecular mechanism underlying carotenoid-based systemic skin photoprotection in SKH-1 mice and provide genetic evidence that photoprotection achieved by the FDA-approved apocarotenoid and food additive bixin depends on NRF2 activation. Bixin activates NRF2 through the critical Cys-151 sensor residue in KEAP1, orchestrating a broad cytoprotective response in cultured human keratinocytes as revealed by antioxidant gene expression array analysis. Following dose optimization studies for cutaneous NRF2 activation by systemic administration of bixin, feasibility of bixin-based suppression of acute cutaneous photodamage from solar UV exposure was investigated in Nrf2(+/+) versus Nrf2(-/-) SKH-1 mice. Systemic administration of bixin suppressed skin photodamage, attenuating epidermal oxidative DNA damage and inflammatory responses in Nrf2(+/+) but not in Nrf2(-/-) mice, confirming the NRF2-dependence of bixin-based cytoprotection. Taken together, these data demonstrate feasibility of achieving NRF2-dependent cutaneous photoprotection by systemic administration of the apocarotenoid bixin, a natural food additive consumed worldwide. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Research Foundation Institute Joint Symposium '97. Ion, marine biotechnology, microgravity, ultrahigh temperature, and laser; Kenkyu kiban shisetsu godo symposium '97. Ion kaiyo bio mujuryoku chokoon laser

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-10

    Presentations were jointly made by NEDO (New Energy and Industrial Technology Development Organization)-financed Ion Engineering Center Corporation, Research Center for the Industrial Utilization of Marine Organisms, Japan Microgravity Center, Japan Ultrahigh Temperature Materials Research Institute, Applied Laser Engineering Center, and organizations annexed to them. The subjects taken up were 'Omnidirectional ion beam technology and titanium ion implantation,' 'Application of ion engineering technology to the prevention of contact allergy,' 'Research on metal/semiconductor transition phase creation for silicon ions,' 'Research on technologies of microalgae-aided CO2 fixation and effective utilization,' 'Construction of gyrB database,' 'Marine microbe-produced antibiotics and assessment of activity,' 'Research on combustion under microgravitational conditions and application to industrial combustors,' 'Research on tube-contained gas/liquid two-phase fluid under microgravitational conditions and application to power generation boiler,' 'Measurement of physical properties of molten semiconductor under microgravitational conditions and research on analysis of heat flow in silicon crystal growing furnace,' 'High temperature oxidation of Mo(Si, Al){sub 2} intermetallic compounds,' 'Development of Nb-based ultrahigh temperature materials,' 'Functional characteristics of Al{sub 2}O{sub 3}/TiC/Ni-based functionally inclined materials,' 'Control of epitaxial crystal growth in CxBE process,' and 'Manufacture of intermetallic compounds by laser plasma hybrid spraying and characteristics.' (NEDO)

  13. At the United Nation Foundation's Social Good Summit, Vice President Biden Announces New Cancer Moonshot International Cooperation and Investments | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    This week, Vice President Joe Biden announced progress on his global vision for the Cancer Moonshot.  Announced were 10 new Memoranda of Understanding or Memoranda of Cooperation for international cancer research and care, as well as new efforts in the emerging scientific areas of precision oncology, the funding of collaborative research centers to address cancer disparities in low- and middle- income (LMIC) countries, and a strengthening of existing U.S. bilateral science and technology engagements around cancer.  

  14. Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury

    Directory of Open Access Journals (Sweden)

    Ravirajsinh N. Jadeja

    2016-01-01

    Full Text Available Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2-related factor 2 (Nrf2, a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury. Several studies indicate that activation of Nrf2 signaling pathway ameliorates liver injury. The hepatoprotective potential of naturally occurring compounds has been investigated in various models of liver injuries. In this review, we comprehensively appraise various phytochemicals that have been assessed for their potential to halt acute and chronic liver injury by enhancing the activation of Nrf2 and have the potential for use in humans.

  15. Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury

    International Nuclear Information System (INIS)

    Hernandez-Montes, Eva; Pollard, Susan E.; Vauzour, David; Jofre-Montseny, Laia; Rota, Cristina; Rimbach, Gerald; Weinberg, Peter D.; Spencer, Jeremy P.E.

    2006-01-01

    Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of γ-glutamylcysteine synthetase-heavy subunit (γ-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis

  16. Introducing the "TCDD-inducible AhR-Nrf2 gene battery".

    Science.gov (United States)

    Yeager, Ronnie L; Reisman, Scott A; Aleksunes, Lauren M; Klaassen, Curtis D

    2009-10-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces genes via the transcription factor aryl hydrocarbon receptor (AhR), including Cyp1a1, NAD(P)H:quinone oxidoreductase 1 (Nqo1), UDP-glucuronosyltransferase 1a6 (Ugt1a6), and glutathione S-transferase a1 (Gsta1). These genes are referred to as the "AhR gene battery." However, Nqo1 is also considered a prototypical target gene of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). In mice, TCDD induction of Nrf2 and Nrf2 target, Nqo1, is dependent on AhR, and thus TCDD induction of drug-processing genes may be routed through an AhR-Nrf2 sequence. There has been speculation that Nrf2 may be involved in the TCDD induction of drug-processing genes; however, the data are not definitive. Therefore, to address whether TCDD induction of Nqo1, Ugts, and Gsts is dependent on Nrf2, we conducted the definitive experiment by administering TCDD (50 mug/kg, ip) to Nrf2-null and wild-type (WT) mice and collecting livers 24 h later to quantify the mRNA of drug-processing genes. TCDD induction of Cyp1a1 and Ugt1a1 was similar in WT and Nrf2-null mice, whereas TCDD induction of Ugt1a5 and 1a9 was blunted in Nrf2-null mice. TCDD induced Nqo1, Ugt1a6, 2b34, 2b35, 2b36, UDP-glucuronic acid-synthesizing gene UDP-glucose dehydrogenase, and Gsta1, m1, m2, m3, m6, p2, t2, and microsomal Gst1 in WT mice but not in Nrf2-null mice. Therefore, the present study demonstrates the novel finding that Nrf2 is required for TCDD induction of classical AhR battery genes Nqo1, Ugt1a6, and Gsta1, as well as most Ugt and Gst isoforms in livers of mice.

  17. Proteomics analysis of dendritic cell activation by contact allergens reveals possible biomarkers regulated by Nrf2

    Energy Technology Data Exchange (ETDEWEB)

    Mussotter, Franz, E-mail: franz.mussotter@bfr.bund.de [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Tomm, Janina Melanie [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); El Ali, Zeina; Pallardy, Marc; Kerdine-Römer, Saadia [INSERM UMR 996, Univ Paris-Sud, Université Paris-Saclay, Chátenay-Malabry (France); Götz, Mario [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany); Bergen, Martin von [Helmholtz Centre for Environmental Research (UFZ), Department of Molecular Systems Biology, Leipzig (Germany); University of Leipzig, Institute of Biochemistry, Leipzig (Germany); Aalborg University, Department of Chemistry and Bioscience, Aalborg (Denmark); Haase, Andrea; Luch, Andreas [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin (Germany)

    2016-12-15

    Allergic contact dermatitis is a widespread disease with high clinical relevance affecting approximately 20% of the general population. Typically, contact allergens are low molecular weight electrophilic compounds which can activate the Keap1/Nrf2 pathway. We performed a proteomics study to reveal possible biomarkers for dendritic cell (DC) activation by contact allergens and to further elucidate the role of Keap1/Nrf2 signaling in this process. We used bone marrow derived dendritic cells (BMDCs) of wild-type (nrf2{sup +/+}) and Nrf2 knockout (nrf2{sup −/−}) mice and studied their response against the model contact sensitizers 2,4-dinitrochlorobenzene (DNCB), cinnamaldehyde (CA) and nickel(II) sulfate by 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) in combination with electrospray ionization tandem mass spectrometry (ESI-MS/MS). Sodium dodecyl sulfate (SDS, 100 μM) served as irritant control. While treatment with nickel(II) sulfate and SDS had only little effects, CA and DNCB led to significant changes in protein expression. We found 18 and 30 protein spots up-regulated in wild-type cells treated with 50 and 100 μM CA, respectively. For 5 and 10 μM DNCB, 32 and 37 spots were up-regulated, respectively. Almost all of these proteins were not differentially expressed in nrf2{sup −/−} BMDCs, indicating an Nrf2-dependent regulation. Among them proteins were detected which are involved in oxidative stress and heat shock responses, as well as in signal transduction or basic cellular pathways. The applied approach allowed us to differentiate between Nrf2-dependent and Nrf2-independent cellular biomarkers differentially regulated upon allergen-induced DC activation. The data presented might contribute to the further development of suitable in vitro testing methods for chemical-mediated sensitization. - Highlights: • Contact allergens induce proteins involved in DC maturation Nrf2-dependently. • Induction of these proteins points to a functional

  18. Research Foundation Institute Joint Symposium '97. Ion, marine biotechnology, microgravity, ultrahigh temperature, and laser; Kenkyu kiban shisetsu godo symposium '97. Ion kaiyo bio mujuryoku chokoon laser

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-10

    Presentations were jointly made by NEDO (New Energy and Industrial Technology Development Organization)-financed Ion Engineering Center Corporation, Research Center for the Industrial Utilization of Marine Organisms, Japan Microgravity Center, Japan Ultrahigh Temperature Materials Research Institute, Applied Laser Engineering Center, and organizations annexed to them. The subjects taken up were 'Omnidirectional ion beam technology and titanium ion implantation,' 'Application of ion engineering technology to the prevention of contact allergy,' 'Research on metal/semiconductor transition phase creation for silicon ions,' 'Research on technologies of microalgae-aided CO2 fixation and effective utilization,' 'Construction of gyrB database,' 'Marine microbe-produced antibiotics and assessment of activity,' 'Research on combustion under microgravitational conditions and application to industrial combustors,' 'Research on tube-contained gas/liquid two-phase fluid under microgravitational conditions and application to power generation boiler,' 'Measurement of physical properties of molten semiconductor under microgravitational conditions and research on analysis of heat flow in silicon crystal growing furnace,' 'High temperature oxidation of Mo(Si, Al){sub 2} intermetallic compounds,' 'Development of Nb-based ultrahigh temperature materials,' 'Functional characteristics of Al{sub 2}O{sub 3}/TiC/Ni-based functionally inclined materials,' 'Control of epitaxial crystal growth in CxBE process,' and 'Manufacture of intermetallic compounds by laser plasma hybrid spraying and characteristics.' (NEDO)

  19. Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.

    Science.gov (United States)

    Yang, Po-Min; Wu, Zhi-Zhen; Zhang, Yu-Qi; Wung, Being-Sun

    2016-06-15

    Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells. We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA. Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished. The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Clinical significance of Keap1 and Nrf2 in oral squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Cong-Fa Huang

    Full Text Available Oxidative stress has been reported to play an important role in progression and prognostication in various kinds of cancers. However, the role and clinical significance of oxidative stress markers Keap1 and Nrf2 in oral squamous cell carcinoma (OSCC has not been elucidated. This study aimed to investigate the correlation of oxidative stress markers Keap1 and Nrf2 expression and pathological features in OSCC by using tissue microarray. Tissue microarrays containing 17 normal oral mucosa, 7 oral epithelial dysplasia and 43 OSCC specimens were studied by immunohistochemistry. The association among these proteins and pathological features were analyzed. Expression of oxidative stress markers Keap1, Nrf2, and antioxidants PPIA, Prdx6, as well as CD147 was found to increase consecutively from normal oral mucosa to OSCC, and the Keap1, Nrf2, PPIA, Prdx6, CD147 expression in OSCC were significantly higher when compared to normal oral mucosa. Expression of Keap1, Nrf2 in tumors was not found to be significantly associated with T category, lymph node metastases, and pathological grade. Furthermore, we checked the relationship among these oxidative stress markers and found that Keap1 was significantly correlated with Nrf2, Prdx6 and CD147. Significant relationship between Nrf2 and Prdx6 was also detected. Finally, we found patients with overexpression of Keap1 and Nrf2 had not significantly worse overall survival by Kaplan-Meier analysis. These findings suggest that ROS markers are associated with carcinogenesis and progression of OSCC, which may have prognostic value and could be regarded as potential therapeutic targets in OSCC.

  1. NRF2 and P73 polymorphisms in Egyptian women with breast cancer

    African Journals Online (AJOL)

    The aim of the study was to assess the role of Nrf2 promoter and P73 G4C14 to A4T14 polymorphisms in breast cancer and the potential relation to the onset of the disease. Eighty six female patients with breast tumor were included in this study. Nrf2 (rs6721961) and p73 (G4A) genetic polymorphisms in promoter and ...

  2. 4-Hydroxy hexenal derived from docosahexaenoic acid protects endothelial cells via Nrf2 activation.

    Directory of Open Access Journals (Sweden)

    Atsushi Ishikado

    Full Text Available Recent studies have proposed that n-3 polyunsaturated fatty acids (n-3 PUFAs have direct antioxidant and anti-inflammatory effects in vascular tissue, explaining their cardioprotective effects. However, the molecular mechanisms are not yet fully understood. We tested whether n-3 PUFAs showed antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a master transcriptional factor for antioxidant genes. C57BL/6 or Nrf2(-/- mice were fed a fish-oil diet for 3 weeks. Fish-oil diet significantly increased the expression of heme oxygenase-1 (HO-1, and endothelium-dependent vasodilation in the aorta of C57BL/6 mice, but not in the Nrf2(-/- mice. Furthermore, we observed that 4-hydroxy hexenal (4-HHE, an end-product of n-3 PUFA peroxidation, was significantly increased in the aorta of C57BL/6 mice, accompanied by intra-aortic predominant increase in docosahexaenoic acid (DHA rather than that in eicosapentaenoic acid (EPA. Human umbilical vein endothelial cells were incubated with DHA or EPA. We found that DHA, but not EPA, markedly increased intracellular 4-HHE, and nuclear expression and DNA binding of Nrf2. Both DHA and 4-HHE also increased the expressions of Nrf2 target genes including HO-1, and the siRNA of Nrf2 abolished these effects. Furthermore, DHA prevented oxidant-induced cellular damage or reactive oxygen species production, and these effects were disappeared by an HO-1 inhibitor or the siRNA of Nrf2. Thus, we found protective effects of DHA through Nrf2 activation in vascular tissue, accompanied by intra-vascular increases in 4-HHE, which may explain the mechanism of the cardioprotective effects of DHA.

  3. Photoprotection by dietary phenolics against melanogenesis induced by UVA through Nrf2-dependent antioxidant responses

    Science.gov (United States)

    Chaiprasongsuk, Anyamanee; Onkoksoong, Tasanee; Pluemsamran, Thanyawan; Limsaengurai, Saowalak; Panich, Uraiwan

    2015-01-01

    Dietary phenolics may play a protective role in UV-mediated skin pigmentation through their antioxidant and UV-absorbing actions. In this study, we investigated whether genetic silencing of Nrf2, regulating the transcription of antioxidant genes, affected melanogenesis in primary human epidermal melanocytes (HEMn) and B16F10 melanoma cells subjected to UVA (8 J/cm2) exposure. Then, we explored the antimelanogenic actions of phenolics; caffeic acid (CA) and ferulic acid (FA) providing partial UVA protection; quercetin (QU) and rutin (RU) providing strong UVA protection and; avobenzone (AV), an efficient UVA filter, in association with modulation of Nrf2-mediated antioxidant defenses in response to UVA insults in B16F10 cells. Upon oxidative insults, Nrf2 silencing promoted melanogenesis in both HEMn and B16F10 cells irradiated with UVA. Stimulation of melanogenesis by UVA correlated with increased ROS and oxidative DNA damage (8-OHdG), GSH depletion as well as a transient downregulation of Nrf2 nuclear translocation and of Nrf2-ARE signaling in B16F10 cells. All test compounds exerted antimelanogenic effects with respect to their abilities to reverse UVA-mediated oxidative damage as well as downregulation of Nrf2 activity and its target antioxidants (GCLC, GST and NQO1) in B16F10 cells. In conclusion, defective Nrf2 may promote melanogenesis under UVA irradiation through oxidative stress mechanisms. Compounds with antioxidant and/or UVA absorption properties could protect against UVA-induced melanogenesis through indirect regulatory effect on Nrf2-ARE pathway. PMID:26765101

  4. Emotional foundations of cognitive control

    Science.gov (United States)

    Inzlicht, Michael; Bartholow, Bruce D.; Hirsh, Jacob B.

    2015-01-01

    Often seen as the paragon of higher cognition, here we suggest that cognitive control is dependent on emotion. Rather than asking whether control is influenced by emotion, we ask whether control itself can be understood as an emotional process. Reviewing converging evidence from cybernetics, animal research, cognitive neuroscience, and social and personality psychology, we suggest that cognitive control is initiated when goal conflicts evoke phasic changes to emotional primitives that both focus attention on the presence of goal conflicts and energize conflict resolution to support goal-directed behavior. Critically, we propose that emotion is not an inert byproduct of conflict but is instrumental in recruiting control. Appreciating the emotional foundations of control leads to testable predictions that can spur future research. PMID:25659515

  5. Emotional foundations of cognitive control.

    Science.gov (United States)

    Inzlicht, Michael; Bartholow, Bruce D; Hirsh, Jacob B

    2015-03-01

    Often seen as the paragon of higher cognition, here we suggest that cognitive control is dependent on emotion. Rather than asking whether control is influenced by emotion, we ask whether control itself can be understood as an emotional process. Reviewing converging evidence from cybernetics, animal research, cognitive neuroscience, and social and personality psychology, we suggest that cognitive control is initiated when goal conflicts evoke phasic changes to emotional primitives that both focus attention on the presence of goal conflicts and energize conflict resolution to support goal-directed behavior. Critically, we propose that emotion is not an inert byproduct of conflict but is instrumental in recruiting control. Appreciating the emotional foundations of control leads to testable predictions that can spur future research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Foundations for microstrip circuit design

    CERN Document Server

    Edwards, Terry

    2016-01-01

    Building on the success of the previous three editions, Foundations for Microstrip Circuit Design offers extensive new, updated and revised material based upon the latest research. Strongly design-oriented, this fourth edition provides the reader with a fundamental understanding of this fast expanding field making it a definitive source for professional engineers and researchers and an indispensable reference for senior students in electronic engineering. Topics new to this edition: microwave substrates, multilayer transmission line structures, modern EM tools and techniques, microstrip and planar transmision line design, transmission line theory, substrates for planar transmission lines, Vias, wirebonds, 3D integrated interposer structures, computer-aided design, microstrip and power-dependent effects, circuit models, microwave network analysis, microstrip passive elements, and slotline design fundamentals.

  7. Static Behaviour of Bucket Foundations

    DEFF Research Database (Denmark)

    Larsen, Kim André

    One new foundation concept in relation to offshore wind turbines is bucket foundations. The concept is known from the oil and gas industry, though the load conditions here are significantly different. The bucket foundation can be used as monopod or e.g. tripod foundations for offshore wind turbines....... The monopod concept is investigated in this thesis, regarding the static behaviour from loads relevant to offshore wind turbines. The main issue in this concept is the rotational stiffness of the foundation and the combined capacity dominated by moments. The vertical bearing capacity of bucket foundations...... theory is proposed. The proposed expression applies to plane strain as well as axis-symmetric stress conditions for foundations with smooth or rough bases. A thorough experimental investigation of the static behaviour of bucket foundations subjected to combined loading is carried out. Laboratory tests...

  8. Unknown foundation determination for scour.

    Science.gov (United States)

    2012-04-01

    Unknown foundations affect about 9,000 bridges in Texas. For bridges over rivers, this creates a problem : regarding scour decisions as the calculated scour depth cannot be compared to the foundation depth, and a : very conservative costly approach m...

  9. Wave Forces on Windturbine Foundations

    DEFF Research Database (Denmark)

    Larsen, Brian Juul; Frigaard, Peter

    A testprogramme has been performed to determine the wave forces on two types of foundations for an offshore windturbine. the tested foundation types are a monopile and cone. Furthermore the shaft of the cone has been tested....

  10. AAA Foundation for Traffic Safety

    Science.gov (United States)

    ... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

  11. Gene expression profiling following NRF2 and KEAP1 siRNA knockdown in human lung fibroblasts identifies CCL11/Eotaxin-1 as a novel NRF2 regulated gene

    Science.gov (United States)

    2012-01-01

    Background Oxidative Stress contributes to the pathogenesis of many diseases. The NRF2/KEAP1 axis is a key transcriptional regulator of the anti-oxidant response in cells. Nrf2 knockout mice have implicated this pathway in regulating inflammatory airway diseases such as asthma and COPD. To better understand the role the NRF2 pathway has on respiratory disease we have taken a novel approach to define NRF2 dependent gene expression in a relevant lung system. Methods Normal human lung fibroblasts were transfected with siRNA specific for NRF2 or KEAP1. Gene expression changes were measured at 30 and 48 hours using a custom Affymetrix Gene array. Changes in Eotaxin-1 gene expression and protein secretion were further measured under various inflammatory conditions with siRNAs and pharmacological tools. Results An anti-correlated gene set (inversely regulated by NRF2 and KEAP1 RNAi) that reflects specific NRF2 regulated genes was identified. Gene annotations show that NRF2-mediated oxidative stress response is the most significantly regulated pathway, followed by heme metabolism, metabolism of xenobiotics by Cytochrome P450 and O-glycan biosynthesis. Unexpectedly the key eosinophil chemokine Eotaxin-1/CCL11 was found to be up-regulated when NRF2 was inhibited and down-regulated when KEAP1 was inhibited. This transcriptional regulation leads to modulation of Eotaxin-1 secretion from human lung fibroblasts under basal and inflammatory conditions, and is specific to Eotaxin-1 as NRF2 or KEAP1 knockdown had no effect on the secretion of a set of other chemokines and cytokines. Furthermore, the known NRF2 small molecule activators CDDO and Sulphoraphane can also dose dependently inhibit Eotaxin-1 release from human lung fibroblasts. Conclusions These data uncover a previously unknown role for NRF2 in regulating Eotaxin-1 expression and further the mechanistic understanding of this pathway in modulating inflammatory lung disease. PMID:23061798

  12. Foundation helps refurbish buildings

    International Nuclear Information System (INIS)

    Camenzind, B.

    2006-01-01

    This article looks at the activities of the Swiss 'Climate-Cent' foundation, which is helping support the energetic refurbishment of building envelopes. The conditions which have to be fulfilled to receive grants are explained. Work supported includes the replacement of windows and the insulation of roofs and attics as well as outside walls. Details on the financial support provided and examples of projects supported are given. The source of the finance needed to provide such support - a voluntary levy on petrol - and further support provided in certain Swiss cantons is commented on

  13. Mathematical foundations of elasticity

    CERN Document Server

    Marsden, Jerrold E

    1994-01-01

    This advanced-level study approaches mathematical foundations of three-dimensional elasticity using modern differential geometry and functional analysis. It is directed to mathematicians, engineers and physicists who wish to see this classical subject in a modern setting with examples of newer mathematical contributions. Prerequisites include a solid background in advanced calculus and the basics of geometry and functional analysis.The first two chapters cover the background geometry ― developed as needed ― and use this discussion to obtain the basic results on kinematics and dynamics of con

  14. Instant Zurb Foundation 4

    CERN Document Server

    Arévalo, Jorge

    2013-01-01

    A quick and easy guide that follows a practical approach to rapidly create responsive web pages using Foundation 4 framework, following the mobile-first philosophy.If you are a web developer who wants to get the most out of your HTML5/CSS/JavaScript skills, this book is ideal for you. It is assumed that you will have some experience with these languages, but for those who don't, you can also be up and running in an instant.

  15. Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    Full Text Available BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5 against 6-hydroxydopamine (6-OHDA- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2 accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1 expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC and heme oxygenase-1 (HO-1, both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment. CONCLUSION: Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.

  16. Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum.

    Science.gov (United States)

    Granado, Noelia; Lastres-Becker, Isabel; Ares-Santos, Sara; Oliva, Idaira; Martin, Eduardo; Cuadrado, Antonio; Moratalla, Rosario

    2011-12-01

    Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analyzed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration. Copyright © 2011 Wiley‐Liss, Inc.

  17. Design, synthesis, and evaluation of curcumin derivatives as Nrf2 activators and cytoprotectors against oxidative death.

    Science.gov (United States)

    Tu, Zhi-Shan; Wang, Qi; Sun, Dan-Dan; Dai, Fang; Zhou, Bo

    2017-07-07

    Activation of nuclear factor erythroid-2-related factor 2 (Nrf2) has been proven to be an effective means to prevent the development of cancer, and natural curcumin stands out as a potent Nrf2 activator and cancer chemopreventive agent. In this study, we synthesized a series of curcumin analogs by introducing the geminal dimethyl substituents on the active methylene group to find more potent Nrf2 activators and cytoprotectors against oxidative death. The geminally dimethylated and catechol-type curcumin analog (compound 3) was identified as a promising lead molecule in terms of its increased stability and cytoprotective activity against the tert-butyl hydroperoxide (t-BHP)-induced death of HepG2 cells. Mechanism studies indicate that its cytoprotective effects are mediated by activating the Nrf2 signaling pathway in the Michael acceptor- and catechol-dependent manners. Additionally, we verified by using copper and iron ion chelators that the two metal ion-mediated oxidations of compound 3 to its corresponding electrophilic o-quinone, contribute significantly to its Nrf2-dependent cytoprotection. This work provides an example of successfully designing natural curcumin-directed Nrf2 activators by a stability-increasing and proelectrophilic strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Identification of a Novel and Potent Nrf2 inhibitor as a Radiosensitizer with High Throughput Screening

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ji Yeon; Park, Sa Rah; Yun, Yeon Sook; Song, Jie Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    Lung cancer is the leading cause of cancer death in both men and women in the United States. Non-small cell lung cancer (NSCLC) accounts for more than 75% of all lung cancers and radiotherapy (RT) is the general treatment modality for these lung cancer patients. Nuclear factor erythroid-2. related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates the expression of genes encoding electrophiles and xenobiotic detoxification enzymes and efflux proteins, which confer cytoprotection against oxidative stress and xenobiotics in normal cells. Kelch-like ECH-associated protein (Keap1) sequesters Nrf2 and leads to proteasomal degradation of Nrf2 in non-stressed condition. Keap1 is often found with biallelic mutation in NSCLC cell lines and NSCLC patients, results in constitutive activation of Nrf2 function, and contributes to resistance of chemotherapy (CT) or RT (3, 4). We thus postulated that inhibition of Nrf2 in cancer cells could increase sensitivity to RT. Our primary results show that IM3829, a putative Nrf2 inhibitor, enhances the efficacy of RT and CT in H1299 lung cancer cell.

  19. Geometric and numerical foundations of movements

    CERN Document Server

    Mansard, Nicolas; Lasserre, Jean-Bernard

    2017-01-01

    This book aims at gathering roboticists, control theorists, neuroscientists, and mathematicians, in order to promote a multidisciplinary research on movement analysis. It follows the workshop “ Geometric and Numerical Foundations of Movements ” held at LAAS-CNRS in Toulouse in November 2015[1]. Its objective is to lay the foundations for a mutual understanding that is essential for synergetic development in motion research. In particular, the book promotes applications to robotics --and control in general-- of new optimization techniques based on recent results from real algebraic geometry.

  20. The foundation of self-esteem.

    Science.gov (United States)

    Bailey, Joseph A

    2003-05-01

    Self-esteem is a simplistic term for varied and complex mental states pertaining to how one views oneself. It takes but little research in the voluminous literature to see the vagueness and inconsistencies in its various definitions. Even more problematic is the uncertainty concerning its foundational components. The importance of having a solid definition and specific ideas about the foundational components of self-esteem is that both pave the way to recognizing its causes; to predicting effects from those causes; and to organizing the trouble-shooting process for locating those philosophical flaws or psychological scars which lead to low self-esteem. The purpose of this paper is to offer a common ground for thinking about self-esteem at its most basic level. In order to distinguish the "basic level" from the rest of the components of self-esteem, let us liken it to a skyscraper building. Here, the focus is on the building's "underground foundation" and the base upon which that foundation rests. The base is a definition that allows for the assessment of the foundation. The underground foundation itself consists of the mental building blocks called self-meaning, self-identity, self-image, and self-concepts. To help illustrate their interactions, a few of the "masks" and "faces" of self-esteem will be mentioned. What is not being addressed is the "above ground structure"--those theories and manifestations dealt with by most mental health specialists.

  1. Problem solving in foundation engineering using foundationPro

    CERN Document Server

    Yamin, Mohammad

    2016-01-01

    This book is at once a supplement to traditional foundation engineering textbooks and an independent problem-solving learning tool. The book is written primarily for university students majoring in civil or construction engineering taking foundation analysis and design courses to encourage them to solve design problems. Its main aim is to stimulate problem solving capability and foster self-directed learning. It also explains the use of the foundationPro software, available at no cost, and includes a set of foundation engineering applications. Taking a unique approach, Dr. Yamin summarizes the general step-by-step procedure to solve various foundation engineering problems, illustrates traditional applications of these steps with longhand solutions, and presents the foundationPro solutions. The special structure of the book allows it to be used in undergraduate and graduate foundation design and analysis courses in civil and construction engineering. The book stands as valuable resource for students, faculty, ...

  2. Mathematical foundations of biomechanics.

    Science.gov (United States)

    Niederer, Peter F

    2010-01-01

    The aim of biomechanics is the analysis of the structure and function of humans, animals, and plants by means of the methods of mechanics. Its foundations are in particular embedded in mathematics, physics, and informatics. Due to the inherent multidisciplinary character deriving from its aim, biomechanics has numerous connections and overlapping areas with biology, biochemistry, physiology, and pathophysiology, along with clinical medicine, so its range is enormously wide. This treatise is mainly meant to serve as an introduction and overview for readers and students who intend to acquire a basic understanding of the mathematical principles and mechanics that constitute the foundation of biomechanics; accordingly, its contents are limited to basic theoretical principles of general validity and long-range significance. Selected examples are included that are representative for the problems treated in biomechanics. Although ultimate mathematical generality is not in the foreground, an attempt is made to derive the theory from basic principles. A concise and systematic formulation is thereby intended with the aim that the reader is provided with a working knowledge. It is assumed that he or she is familiar with the principles of calculus, vector analysis, and linear algebra.

  3. The science of sex and gender in human health: online courses to create a foundation for sex and gender accountability in biomedical research and treatment.

    Science.gov (United States)

    Plank-Bazinet, Jennifer L; Sampson, Annie; Miller, Leah R; Fadiran, Emmanuel O; Kallgren, Deborah; Agarwal, Rajeev K; Barfield, Whitney; Brooks, Claudette E; Begg, Lisa; Mistretta, Amy C; Scott, Pamela E; Clayton, Janine Austin; Cornelison, Terri L

    2016-01-01

    Sex and gender differences play a significant role in the course and outcome of conditions that affect specific organ systems in the human body. Research on differences in the effects of medical intervention has helped scientists develop a number of sex- and gender-specific guidelines on the treatment and management of these conditions. An online series of courses, "The Science of Sex and Gender in Human Health," developed by the National Institutes of Health Office of Research on Women's Health and the U.S. Food and Drug Administration Office of Women's Health, examines sex and gender differences and their implications. Thus far, three online courses have been generated. The first course offers an overview of the scientific and biological basis for sex- and gender-related differences. The second course is focused on disease-specific sex and gender differences in health and behavior and their implications. Finally, the third course covers the influence of sex and gender on disease manifestation, treatment, and outcome. Data were obtained using website analytics and post-course surveys. To date, over 1000 individuals have completed at least one course. Additionally, 600 users have received continuing education credit for completing a course in the series. Finally, the majority of respondents to the online course survey have indicated that the courses considerably enhanced their professional effectiveness. "The Science of Sex and Gender in Human Health" online courses are freely available sources of information that provide healthcare providers and researchers with the resources to successfully account for sex and gender in their medical practice and research programs.

  4. Watershed Watch: The Importance of Mentors in Student-driven Full Inquiry Undergraduate Research Projects as the Foundation for an Introductory Course in Biogeoscience

    Science.gov (United States)

    Rock, B. N.; Hale, S. R.; Graham, K. J.; Hayden, L.; Barber, L.; Perry, C.; Schloss, J.; Sullivan, E.; Yuan, J.; Abebe, E.; Mitchell, L.; Abrams, E.; Gagnon, M.

    2008-12-01

    Watershed Watch (NSF 0525433) engages early undergraduate students from two-year and four-year colleges in student-driven full inquiry-based instruction in the biogeosciences. Program goals for Watershed Watch are to test if inquiry-rich student-driven projects sufficiently engage undeclared students (or noncommittal STEM majors) to declare a STEM major (or remain with their STEM major). A significant component of this program is an intensive two-week Summer course, in which undeclared freshmen research various aspects of a local watershed. Students develop their own research questions and study design, collect and analyze data, and produce a scientific or an oral poster presentation. The course objectives, curriculum and schedule are presented as a model for dissemination for other institutions and programs seeking to develop inquiry-rich courses designed to attract students into biogeoscience disciplines. Data from self-reported student feedback indicated the most important factors explaining high-levels of student motivation and research excellence in the course are 1) working with committed, energetic, and enthusiastic faculty mentors; and 2) faculty mentors demonstrating high degrees of teamwork and coordination.

  5. Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis.

    Directory of Open Access Journals (Sweden)

    Ning Chen

    Full Text Available To explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis.Western blot, immunohistochemistry(IHC and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism.Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods. (p< 0.05. However, there was no statistical difference in Nrf2 mRNA expression levels between the adenomyosis and control groups. Using an agonist and Nrf2 siRNA, we regulated the Nrf2 protein levels of primary cultured endometrial glandular cells. With increased expression of Nrf2, cell scratch assay showed that the agonist-treated group migrated significantly faster than the control group, with MMP9 protein level markedly elevated. In contrast, Nrf2 siRNA-treated group migrated slower than the control group, with decreased expression of MMP9 protein. All of the scratching healing spaces and protein levels between the treated and control groups were statistically significant (p< 0.05.Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis. Specified reduction of Nrf2 expression could prove to be a new therapeutic target in the clinical treatment of adenomyosis.

  6. Industrial Foundations as Long‐term Owners

    DEFF Research Database (Denmark)

    Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

    2018-01-01

    Research Question/Issue: Does foundation ownership lead to long‐term corporate governance and business behavior in foundation‐owned companies? Research Findings/Insights: Short‐termism has become a serious concern for corporate governance, and this has inspired a search for institutional...... that practice long‐term governance.We show that foundation ownership is highly stable compared to other ownership structures. Foundation‐owned companies replace managers less frequently. They have conservative capital structures with low financial leverage. They score higheron an index of long......‐termism in finance, investment, and employment. They survivelonger. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures, and particularly that industrial foundations possess characteristics that promote long‐termism. Policymakers, business owners...

  7. Implementation of a new Foundations Concept for Offshore Wind Farms

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo

    2008-01-01

    The foundation principles for the recent major offshore wind farm projects in Europe have been dominated by two types of foundation solutions, the gravitational foundation and the monopile. A fully operational 3.0 MW offshore wind turbine was installed on a prototype of the bucket foundation...... at the test field in Frederikshavn in December 2002. A five-year research and development project has proven the bucket foundation to be feasible in suitable soil conditions in water depth from near shore to approximately 40 meters. The bucket foundation design reduces the steel weight by half compared...... with a traditional monopile solution and the installation of the bucket foundation is much easier and does not require heavy installation equipment. In this paper the full-scale field installation of the prototype is described. A design procedure has been developed in cooperation with the certifying party in order...

  8. Elucidation of the therapeutic role of mitochondrial biogenesis transducers NRF-1 in the regulation of renal fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Pei-Fang [Graduate Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Liu, Shu-Fen [Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan (China); Hung, Tsung-Jen [Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Hung, Chien-Ya [Department of Food Nutrition, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Liu, Guo-Zheng [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Chuang, Lea-Yea [Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Chen, Mei-Fen [Department of Acupressure Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Wang, Jue-Long [Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Taiwan (China); Shi, Ming-Der [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Department of Medical Technology, Kaohsiung Veterans General Hospital Tainan Branch, Tainan, Taiwan (China); Hsu, Chen Hung [Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Shiue, Yow-Ling, E-mail: shiue.shirley@gmail.com [Graduate Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China); Yang, Yu-Lin, E-mail: Call0955443221@gmail.com [Graduate Institute of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan (China); Graduate Institute of Biomedical Science, Chung Hwa University of Medical Technology, Tainan, Taiwan (China)

    2016-11-15

    Background: Mitochondrial dysfunction is a newly established risk factor for the development of renal fibrosis. Cell survival and injury repair is facilitated by mitochondrial biogenesis. Nuclear respiratory factor 1 (NRF-1) is a transcriptional regulation factor that plays a central role in the regulation of mitochondrial biogenesis. However, the transcription factor of this process in renal fibrosis is unknown. Thus, we hereby discussed the correlations of NRF-1 and renal interstitial fibrosis. Materials and methods: In vitro fibrosis model was established by treatment with transforming growth factor-β1 (TGF-β1) in NRK-49F (Normal Rat kidney fibroblast). We investigated the ROS production, mitochondrial biogenesis and fibrogenic marker (e.q. fibronectin) during the progression of renal fibrosis by kit and Western blotting assay. Here, we used that two distinct mechanisms regulate NRF-1 activation and degradation of NRF-1. NRF-1 was transfect by pcDNA-NRF-1 overexpression gene to evaluate the NRF-1 activity of the therapeutic effect in renal fibrosis. In addition, NRF-1 was silenced by shRNA-NRF-1 to evaluate the significance of NRF-1. ELISA was used to evaluate the secreted fibronectin. Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin, NRF-1). Results: Under renal fibrosis conditions, TGF-β1 (5 ng/ml) increased ROS. Simultaneously, TGF-β1-induced extracellular fibronectin by ELISA assay. In addition, TGF-β1 decreased expression of mitochondrial biogenesis. This is the first time to demonstrate that expression of NRF-1 is significantly decreased in renal fibrosis. However, NRK49F was a transfection with pcDNA-NRF-1 (2 μg/ml) expression vector dramatically reverse TGF-β1-induced cellular fibrosis concomitantly with the suppression of fibronectin (both intracellular and extracellular fibronectin). More importantly, transfection with shRNA-NRF-1 (2 μg/ml) significantly increased the expression of fibronectin

  9. Generation of a Nrf2 homozygous knockout human embryonic stem cell line using CRISPR/Cas9

    Directory of Open Access Journals (Sweden)

    So-Jung Kim

    2017-03-01

    Full Text Available Nuclear factor erythroid 2-related factor 2 (NFE2L2 or Nrf2 is a well-known transcription factor that regulates the expression of a large number of anti-oxidant genes in mammalian cells (J.H. Kim et al., 2014. Here, we generated a homozygous Nrf2 knockout human embryonic stem cell (hESC line, H9Nrf2KO-A13, using the CRISPR/Cas9 genome editing method. The Nrf2 homozygous knockout H9 cell line maintains pluripotency, differentiation potential into three germ layers, and a normal karyotype.

  10. Stabilization of Nrf2 protein by D3T provides protection against ethanol-induced apoptosis in PC12 cells.

    Directory of Open Access Journals (Sweden)

    Jian Dong

    2011-02-01

    Full Text Available Previous studies have demonstrated that maternal ethanol exposure induces a moderate increase in Nrf2 protein expression in mouse embryos. Pretreatment with the Nrf2 inducer, 3H-1, 2-dithiole-3-thione (D3T, significantly increases the Nrf2 protein levels and prevents apoptosis in ethanol-exposed embryos. The present study, using PC12 cells, was designed to determine whether increased Nrf2 stability is a mechanism by which D3T enhances Nrf2 activation and subsequent antioxidant protection. Ethanol and D3T treatment resulted in a significant accumulation of Nrf2 protein in PC 12 cells. CHX chase analysis has shown that ethanol treatment delayed the degradation of Nrf2 protein in PC12 cells. A significantly greater decrease in Nrf2 protein degradation was observed in the cells treated with D3T alone or with both ethanol and D3T. In addition, D3T treatment significantly reduced ethanol-induced apoptosis. These results demonstrate that the stabilization of Nrf2 protein by D3T confers protection against ethanol-induced apoptosis.

  11. Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis.

    Science.gov (United States)

    Chen, Ning; Du, Baoying; Zhou, Hao; Shen, Fengxian; Li, Juan; Xie, Zhenwei

    2017-01-01

    To explore the expression level of Nrf2 in adenomyosis and study the mechanism of abnormal expression of Nrf2 in the pathogenesis of adenomyosis. Western blot, immunohistochemistry(IHC) and real time PCR were used to measure Nrf2 expression levels in tissue and cell samples. Knockdown and overexpression of Nrf2 were used to investigate the variation of migration ability of endometrial glandular cells as well as the regulatory mechanism. Nrf2 protein levels were significantly higher in the eutopic and ectopic endometrial glands when compared with control cases using IHC and western blot methods. (pendometrial glandular cells. With increased expression of Nrf2, cell scratch assay showed that the agonist-treated group migrated significantly faster than the control group, with MMP9 protein level markedly elevated. In contrast, Nrf2 siRNA-treated group migrated slower than the control group, with decreased expression of MMP9 protein. All of the scratching healing spaces and protein levels between the treated and control groups were statistically significant (p< 0.05). Abnormal expression of Nrf2 may play an important role in the pathogenesis and development of adenomyosis. Specified reduction of Nrf2 expression could prove to be a new therapeutic target in the clinical treatment of adenomyosis.

  12. [Foundation of the science and society alliance in France. Towards a conscious and recognised collaboration between actors of research and civil society].

    Science.gov (United States)

    Fellini, Nadia; Faroult, Elie

    2015-01-01

    In the last two decades, the debate on the meaning of science in relation to societies that create it, nourish it, and benefit from it, focused on civil society's ability to produce knowledge. This yielded first the concept of participatory science and later the wider concept of participatory research. Throughout Europe, numerous collective experimentations have generated countless interactions, and new interfaces between the world of research and civil society are constantly being created. But in spite of the proliferation of these experiences, a paradox slows down their acknowledgment and legitimation. On the one hand, these interactions often go unseen and unrecognized by the institutions, public policies, and even at times their very creators. On the other hand, scientists, are still overwhelmingly wary of civil society and, perceiving only its intellectual deficit and lack of comprehension, they fail to consider the study and development of these interactions as being of primary importance. The Sciences and Society Alliance, which was recently founded in France, provides a platform where these collaborative experiences can be collected, studied, supported, communicated, and institutionally acknowledged. The launch of this process,which is soon to be European in scope, answers the need to bring science into the democratic path tread by the societies that create it. In its ability to compose diversity, this process is an example of deep democracy.

  13. The Impact of an Interactive Statistics Module on Novices' Development of Scientific Process Skills and Attitudes in a First-Semester Research Foundations Course.

    Science.gov (United States)

    Marsan, Lynnsay A; D'Arcy, Christina E; Olimpo, Jeffrey T

    2016-12-01

    Evidence suggests that incorporating quantitative reasoning exercises into existent curricular frameworks within the science, technology, engineering, and mathematics (STEM) disciplines is essential for novices' development of conceptual understanding and process skills in these domains. Despite this being the case, such studies acknowledge that students often experience difficulty in applying mathematics in the context of scientific problems. To address this concern, the present study sought to explore the impact of active demonstrations and critical reading exercises on novices' comprehension of basic statistical concepts, including hypothesis testing, experimental design, and interpretation of research findings. Students first engaged in a highly interactive height activity that served to intuitively illustrate normal distribution, mean, standard deviation, and sample selection criteria. To enforce practical applications of standard deviation and p -value, student teams were subsequently assigned a figure from a peer-reviewed primary research article and instructed to evaluate the trustworthiness of the data. At the conclusion of this exercise, students presented their evaluations to the class for open discussion and commentary. Quantitative assessment of pre- and post-module survey data indicated a statistically significant increase both in students' scientific reasoning and process skills and in their self-reported confidence in understanding the statistical concepts presented in the module. Furthermore, data indicated that the majority of students (>85%) found the module both interesting and helpful in nature. Future studies will seek to develop additional, novel exercises within this area and to evaluate the impact of such modules across a variety of STEM and non-STEM contexts.

  14. Completion Summary for Well NRF-16 near the Naval Reactors Facility, Idaho National Laboratory, Idaho

    Science.gov (United States)

    Twining, Brian V.; Fisher, Jason C.; Bartholomay, Roy C.

    2010-01-01

    In 2009, the U.S. Geological Survey in cooperation with the U.S. Department of Energy's Naval Reactors Laboratory Field Office, Idaho Branch Office cored and completed well NRF-16 for monitoring the eastern Snake River Plain (SRP) aquifer. The borehole was initially cored to a depth of 425 feet below land surface and water samples and geophysical data were collected and analyzed to determine if well NRF-16 would meet criteria requested by Naval Reactors Facility (NRF) for a new upgradient well. Final construction continued after initial water samples and geophysical data indicated that NRF-16 would produce chemical concentrations representative of upgradient aquifer water not influenced by NRF facility disposal, and that the well was capable of producing sustainable discharge for ongoing monitoring. The borehole was reamed and constructed as a Comprehensive Environmental Response Compensation and Liability Act monitoring well complete with screen and dedicated pump. Geophysical and borehole video logs were collected after coring and final completion of the monitoring well. Geophysical logs were examined in conjunction with the borehole core to identify primary flow paths for groundwater, which are believed to occur in the intervals of fractured and vesicular basalt and to describe borehole lithology in detail. Geophysical data also were examined to look for evidence of perched water and the extent of the annular seal after cement grouting the casing in place. Borehole videos were collected to confirm that no perched water was present and to examine the borehole before and after setting the screen in well NRF-16. Two consecutive single-well aquifer tests to define hydraulic characteristics for well NRF-16 were conducted in the eastern SRP aquifer. Transmissivity and hydraulic conductivity averaged from the aquifer tests were 4.8 x 103 ft2/d and 9.9 ft/d, respectively. The transmissivity for well NRF-16 was within the range of values determined from past aquifer

  15. Role of the Nrf2-heme oxygenase-1 pathway in silver nanoparticle-mediated cytotoxicity

    International Nuclear Information System (INIS)

    Kang, Su Jin; Ryoo, In-geun; Lee, Young Joon; Kwak, Mi-Kyoung

    2012-01-01

    Silver nanoparticles (nano-Ag) have been widely used in various commercial products including textiles, electronic appliances and biomedical products. However, there remains insufficient information on the potential risk of nano-Ag to human health and environment. In the current study, we have investigated the role of NF-E2-related factor 2 (Nrf2) transcription factor in nano-Ag-induced cytotoxicity. When Nrf2 expression was blocked using interring RNA expression in ovarian carcinoma cell line, nano-Ag treatment showed a substantial decrease in cell viability with concomitant increases in apoptosis and DNA damage compared to the control cells. Target gene analysis revealed that the expression of heme oxygenase-1 (HO-1) was highly elevated by nano-Ag in nonspecific shRNA expressing cells, while Nrf2 knockdown cells (NRF2i) did not increase HO-1 expression. The role of HO-1 in cytoprotection against nano-Ag was reinforced by results using pharmacological inducer of HO-1: cobalt protoporphyrin-mediated HO-1 activation in the NRF2i cells prevented nano-Ag-mediated cell death. Similarly, pharmacological or genetic inhibition of HO-1 in nonspecific control cells exacerbated nano-Ag toxicity. As the upstream signaling mechanism, nano-Ag required the phosphoinositide 3-kinase (PI3K) and p38MAPK signaling cascades for HO-1 induction. The treatment with either PI3K inhibitor or p38MAPK inhibitor suppressed HO-1 induction and intensified nano-Ag-induced cell death. Taken together, these results suggest that Nrf2-dependent HO-1 up-regulation plays a protective role in nano-Ag-induced DNA damage and consequent cell death. In addition, nano-Ag-mediated HO-1 induction is associated with the PI3K and p38MAPK signaling pathways. -- Highlights: ► Role of Nrf2 signaling in silver nanoparticle toxicity. ► Silver nanoparticle toxicity is increased by Nrf2 blockade. ► Nrf2-dependent HO-1 induction protects cells from silver nanoparticle toxicity. ► PI3K and p38MAPK cascades are

  16. Physical Foundations of Cosmology

    International Nuclear Information System (INIS)

    Stewart, J M

    2006-01-01

    In 1952, Mme Yvonne Choquet-Bruhat published a major paper, Theoreme d'existence pour certains systemes d'equations aux derivees partielles non lineaires (Acta Math. 88 141-225), which laid the foundation for modern studies of the Cauchy problem in general relativity. The fiftieth anniversary of this event was celebrated with an eponymous Cargese Summer School in 2002. The proceedings of that summer school are summarized electronically (as audio, video, transparencies and lecture notes, where available) on a DVD archive included with this volume, and are also available on the internet. However the organizers decided that a separate volume describing the 'state of the art in mathematical general relativity' would be useful, and this book is the result. It includes some material not covered in the school and excludes some school material which has been covered adequately elsewhere. About one fifth of the book is devoted to a survey of Smoothness at Null Infinity and the Structure of Initial Data by Helmut Friedrich. This is a modern study of gravitational radiation, and the analysis of Einstein's equations. It is extremely helpful to survey all of this material, including some of the latest developments, using a consistent notation. This article is strongly recommended to anyone hoping to gain a foothold in this area. Lars Andersson has surveyed, in The Global Existence Problem in General Relativity, some results and conjectures about the global properties of 3+1-dimensional spacetimes with a compact Cauchy surface. Again it is very useful to have essentially all of the known results presented in a consistent notation. This material is not on the DVD. Yvonne Choquet-Bruhat has contributed a long research paper, Future Complete U(1) Symmetric Einsteinian Spacetimes, the Unpolarized Case. There is a non-linear stability theorem due to her and Vincent Moncrief in which spacetime is of the form M x R where M is a circle bundle over a compact orientable surface of genus

  17. Assessment of scientific programs: a necessary procedure for Brazilian scientific policy - the Young Investigator Program of the State of São Paulo Research Foundation

    Directory of Open Access Journals (Sweden)

    Carlos A. de Pian

    2007-09-01

    Full Text Available Programs of Science and Technology research have grown significantly in Brazil over the last decades. Until the 1980s the so-called undirected programs, without specific goals and requiring only scientific merit, prevailed. The few programs with defined goals in this period were never objectively assessed. The same situation occurred in developed countries. In the early 1990s, the assessment of programs supported by public funding became mandatory in US and some European countries. In Brazil, program assessment has so far not been implemented yet. The Fundação de Amparo à Pesquisa no Estado de São Paulo (FAPESP (Brazilian funding agency Young Investigator (YI Program is in its eleventh year, with approximately eight hundred projects awarded. Although it is free-demand based as concerns areas of knowledge, it has specific goals : (1 conceding grants to YI in view of the balance between funding, merit and real needs so as to enable satisfactory working conditions in the short term, (2 providing priority for institutions with a less extensive background in research, (3 granting a special fellowship to YI with no employment connection and (4 introduction of new research fronts in centers with a sound research background. This assessment provided evidence for the achievement of first three goals. The fourth one is still pending on additional data requiring survey assessment. Actions in this direction are recommended.Programas de Ciência e Tecnologia cresceram significativamente no Brasil nas últimas décadas. Até a década de 80 os assim chamados programas não dirigidos, sem metas específicas e requerendo apenas mérito científico prevaleciam. Os poucos programas com metas definidas neste período não foram jamais objetivamente avaliados. A mesma situação ocorria nos países desenvolvidos. No início da década de 90, a avaliação de programas dependentes de recursos públicos tornou-se mandatória nos Estados Unidos e em alguns pa

  18. Challenges and Ideas to Achieve Wireless 100 Gb/s Transmission: An Overview of Challenges and Solutions within the German Research Foundation (DFG) Special Priority Program SPP1655

    Science.gov (United States)

    Kraemer, Rolf

    2017-09-01

    Wireless communications is one of the fastest growing technology fields, driving numerous other innovations in electronics. One challenging research area within the wireless field is to achieve much higher transmission rates. First products with up to 3 Gb/s are in the market. In the coming years we predict this speed growing quickly up to and beyond 100 Gb/s. Today it is an open question how we can realize a wireless system at this speed. If we intend to use such systems in a mobile environment, we can only afford to spend approximately 1-10 pW/b for the end-to-end communication. This includes RF-transmission and all processing and protocol steps. The SPP1655 of the DFG was set up to investigate new paradigms for achieving the 100 Gb/s wireless transmission goal. Within 11 coordinated projects researchers from all over Germany are addressing several relevant issues ranging from the antennas and RF-Frontend, baseband-processing and error correction to protocol processing. A number of limitations of current approaches have to be investigated and new algorithms must be found in order to achieve the intended goal. One of the big challenges is finding the correct balance between analog and digital signal processing to achieve an extremely high performance at very low energy consumption. Another challenge is to find a good balance between bandwidth and bandwidth efficiency to achieve the 100 Gbps goal. Finally, protocol processing will need new approaches to decouple the central processor of a computer from the high-end input/output operations. Within this editorial we will address the main challenges and briefly outline the approaches of the running projects. The rest of this special issue will be devoted to more detailed descriptions and achievements of the individual projects of SPP1655.

  19. Developing a Child and Youth Mental Health and Addictions Framework for Yukon as a Foundation for Policy Reform: Engaging Stakeholders Through a Policy and Research Partnership

    Directory of Open Access Journals (Sweden)

    Gillian Mulvale

    2016-09-01

    Full Text Available In April 2015 the Yukon Government released a new child and youth mental health and addictions framework (CYMHAF to improve territory-wide access to basic mental health care and coordination of services for children and families. Yukon’s limited resource base and dispersed population challenges delivery of child and youth mental health and addictions services to small rural communities where needs are often high as a legacy of residential school policies. The objective of CYMHAF is to improve outcomes by identifying and capitalizing on current strengths, and reallocating existing resources to better meet the mental health needs of Yukon youth and families. Access, coordination and quality problems associated with existing services, growing public awareness of mental health issues, and a new national policy framework designed to assist provinces and territories, led Yukon policy makers to partner with researchers to capitalize on a Canadian Institutes of Health Research (CIHR strategic grant initiative. CYMHAF was based on extensive stakeholder engagement, best evidence and advice from key informants in other jurisdictions, and offers a cascading model of service delivery through which basic mental health care can be provided by existing health and human service workers in communities. These workers will be trained in child and youth mental health competencies, and will have electronic linkages and support to integrated teams of primary care providers who will be located in regional hubs once fully implemented, and to specialists in Whitehorse and out of Territory. Implementation is underway with some training of front line Health and Social Service and First Nations workers, a new mental wellness strategy for Yukon founded on CYMHAF scheduled for release in spring 2016, and may be accelerated by federal government promises of a new Health Accord and a new relationship with indigenous people.

  20. The Impact of an Interactive Statistics Module on Novices’ Development of Scientific Process Skills and Attitudes in a First-Semester Research Foundations Course

    Directory of Open Access Journals (Sweden)

    Lynnsay A. Marsan

    2016-12-01

    Full Text Available Evidence suggests that incorporating quantitative reasoning exercises into existent curricular frameworks within the science, technology, engineering, and mathematics (STEM disciplines is essential for novices’ development of conceptual understanding and process skills in these domains. Despite this being the case, such studies acknowledge that students often experience difficulty in applying mathematics in the context of scientific problems. To address this concern, the present study sought to explore the impact of active demonstrations and critical reading exercises on novices’ comprehension of basic statistical concepts, including hypothesis testing, experimental design, and interpretation of research findings. Students first engaged in a highly interactive height activity that served to intuitively illustrate normal distribution, mean, standard deviation, and sample selection criteria. To enforce practical applications of standard deviation and p-value, student teams were subsequently assigned a figure from a peer-reviewed primary research article and instructed to evaluate the trustworthiness of the data. At the conclusion of this exercise, students presented their evaluations to the class for open discussion and commentary. Quantitative assessment of pre- and post-module survey data indicated a statistically significant increase both in students’ scientific reasoning and process skills and in their self-reported confidence in understanding the statistical concepts presented in the module. Furthermore, data indicated that the majority of students (>85% found the module both interesting and helpful in nature. Future studies will seek to develop additional, novel exercises within this area and to evaluate the impact of such modules across a variety of STEM and non-STEM contexts.

  1. Foundations of signal processing

    CERN Document Server

    Vetterli, Martin; Goyal, Vivek K

    2014-01-01

    This comprehensive and engaging textbook introduces the basic principles and techniques of signal processing, from the fundamental ideas of signals and systems theory to real-world applications. Students are introduced to the powerful foundations of modern signal processing, including the basic geometry of Hilbert space, the mathematics of Fourier transforms, and essentials of sampling, interpolation, approximation and compression. The authors discuss real-world issues and hurdles to using these tools, and ways of adapting them to overcome problems of finiteness and localisation, the limitations of uncertainty and computational costs. Standard engineering notation is used throughout, making mathematical examples easy for students to follow, understand and apply. It includes over 150 homework problems and over 180 worked examples, specifically designed to test and expand students' understanding of the fundamentals of signal processing, and is accompanied by extensive online materials designed to aid learning, ...

  2. Logical foundation of quantum mechanics

    International Nuclear Information System (INIS)

    Stachow, E.W.

    1980-01-01

    The subject of this article is the reconstruction of quantum mechanics on the basis of a formal language of quantum mechanical propositions. During recent years, research in the foundations of the language of science has given rise to a dialogic semantics that is adequate in the case of a formal language for quantum physics. The system of sequential logic which is comprised by the language is more general than classical logic; it includes the classical system as a special case. Although the system of sequential logic can be founded without reference to the empirical content of quantum physical propositions, it establishes an essential part of the structure of the mathematical formalism used in quantum mechanics. It is the purpose of this paper to demonstrate the connection between the formal language of quantum physics and its representation by mathematical structures in a self-contained way. (author)

  3. The openEHR Foundation.

    Science.gov (United States)

    Kalra, Dipak; Beale, Thomas; Heard, Sam

    2005-01-01

    The openEHR Foundation is an independent, not-for-profit organisation and community, facilitating the creation and sharing of health records by consumers and clinicians via open-source, standards-based implementations. It was formed as a union of ten-year international R&D efforts in specifying the requirements, information models and implementation of comprehensive and ethico-legally sound electronic health record systems. Between 2000 and 2004 it has grown to having an on-line membership of over 300, published a wide range of EHR information viewpoint specifications. Several groups have now begun collaborative software development, within an open source framework. This chapter summarises the formation of openEHR, its research underpinning, practical demonstrators, the principle design concepts, and the roles openEHR members are playing in international standards.

  4. Mathematical foundation of quantum mechanics

    CERN Document Server

    Parthasarathy, K R

    2005-01-01

    This is a brief introduction to the mathematical foundations of quantum mechanics based on lectures given by the author to Ph.D.students at the Delhi Centre of the Indian Statistical Institute in order to initiate active research in the emerging field of quantum probability. The material in the first chapter is included in the author's book "An Introduction to Quantum Stochastic Calculus" published by Birkhauser Verlag in 1992 and the permission of the publishers to reprint it here is acknowledged. Apart from quantum probability, an understanding of the role of group representations in the development of quantum mechanics is always a fascinating theme for mathematicians. The first chapter deals with the definitions of states, observables and automorphisms of a quantum system through Gleason's theorem, Hahn-Hellinger theorem and Wigner's theorem. Mackey's imprimitivity theorem and the theorem of inducing representations of groups in stages are proved directly for projective unitary antiunitary representations ...

  5. Activities of the National Academy of Sciences in relation to the Radiation Effects Research Foundation. Annual performance report, June 1, 1991--May 31, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Edington, C.W.

    1992-06-01

    This progress report relates progress in the various research projects evaluating the late health effects, both somatic and genetic, resulting from radiation exposure of the survivors of the atomic bombs at Hiroshima and Nagasaki, Japan. Considerable progress has been made in the collection and utilization of the various epidemiological data bases. These include the Life Span Study, (LSS) cohort, the Adult Health Study (AHS) cohort, the In Utero cohort, the leukemia registry and the F-1 Study population. Important progress has been made in using RERF Tumor and Tissue Registry records for evaluation of cancer incidence and radiation risk estimates for comparison with cancer mortality and risk in the LSS cohort. At the present time, a manuscript on the incidence of solid tumors (1950-1987) is undergoing internal and external review for publication as an RERF Technical report (TR) and for publication in a peer-reviewed scientific journal. In addition, manuscripts are in preparation on (1) a comprehensive report on the incidence of hematological cancers, including analysis of leukemia by cell type (1950-1987), (2) a general description of Tumor Registry operations and (3) a comparison of incidence- and mortality-based estimates of radiation risk in the LSS cohort.

  6. Current Empirical Premises to the Disclosure of the Secrets of Property in Law: A Foundation and a Guideline for Future Research

    Directory of Open Access Journals (Sweden)

    Geir Stenseth

    2008-12-01

    Full Text Available This article presents an empirical legal study in the field of property theory. I take as my point of departure the perspective of exclusion. Such a basic perspective falls short, however, when we conceptualize the exceptions from the exclusion rule. In this respect, a diversified set of considerations and concerns claims attention, including the nature of the relationship between the possessor and the object in question. This research digs into the new achievements in the fields of economics and life sciences, investigating the validity and relevance of arguments which may be derived from the possessor-object dimension. The findings suggest a differentiated view on how people comprehend various situations of possession, and the article proposes a gradual theoretical model for shaping and managing the legal concept of property in this respect. Finally, I indicate some practical legal topics which may take advantage of the model (e.g. the field of expropriation, the problem of whether a possession should be protected by a property rule or by a liability rule, and the problems related to property as a human right.

  7. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jeong Su [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2015-10-09

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  8. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    Science.gov (United States)

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.

  9. Concerted action of p62 and Nrf2 protects cells from palmitic acid-induced lipotoxicity

    International Nuclear Information System (INIS)

    Park, Jeong Su; Kang, Dong Hoon; Lee, Da Hyun; Bae, Soo Han

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and diabetes mellitus, is caused by the accumulation of excess fatty acids within liver cells. Palmitic acid (PA), a common saturated fatty acid found in mammals, induces the generation of reactive oxygen species (ROS) and elicits apoptotic cell death, known as lipotoxicity. However, protective mechanisms against PA-induced lipotoxicity have not been elucidated. In this study, we aimed to clarify the role of p62, an adapter protein in the autophagic process, as well as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in protecting cells from PA-induced lipotoxicity. The Nrf2-Keap1 pathway is essential for the protection of cells from oxidative stress. p62 enhances its binding to Keap1 and leads to Nrf2 activation. Here, we show that PA potentiates Keap1 degradation and thereby activates the transcription of Nrf2 target genes partially through autophagy. Furthermore, this PA-mediated Keap1 degradation depends on p62. Correspondingly, a lack of p62 attenuates the PA-mediated Nrf2 activation and increases the susceptibility of cells to oxidative stress. These results indicate that p62 plays an important role in protecting cells against lipotoxicity through Keap1 degradation-mediated Nrf2 activation. - Highlights: • PA induces Keap1 downregulation and activates Nrf2 target gene transcription. • PA-induced Keap1 degradation is partly mediated by the autophagic pathway. • PA-induced Keap1 degradation depends on p62. • Ablation of p62 exacerbates PA-mediated apoptotic cell death.

  10. Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Chian, Song; Thapa, Ruby; Chi, Zhexu [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Wang, Xiu Jun [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Tang, Xiuwen, E-mail: xiuwentang@zju.edu.cn [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China)

    2014-05-16

    Highlights: • Luteolin inhibits the Nrf2 pathway in mouse liver and in xenografted tumors. • Luteolin markedly inhibits the growth of xenograft tumors. • Luteolin enhances the anti-cancer effect of cisplatin in mice in vivo. • Luteolin could serve as an adjuvant in the chemotherapy of NSCLC. - Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many types of tumor, promotes tumor growth, and confers resistance to anticancer therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer. Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro. Here, we showed that luteolin reduced the constitutive expression of NAD(P)H quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner. Further, luteolin inhibited the expression of antioxidant enzymes and glutathione transferases, decreasing the reduced glutathione in the liver of wild-type mice under both constitutive and butylated hydroxyanisole-induced conditions. In contrast, such distinct responses were not detected in Nrf2{sup −/−} mice. In addition, oral administration of luteolin, either alone or combined with intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549 cells grown subcutaneously in athymic nude mice. Cell proliferation, the expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin. Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in vivo and can serve as an adjuvant in the chemotherapy of NSCLC.

  11. Installation of foundation fieldbus to KUR

    International Nuclear Information System (INIS)

    Ishihara, Shinji; Fujita, Yoshiaki

    1999-11-01

    The instrumentation and control system for the research reactor in Research Reactor Institute, Kyoto University has been used for the safe and steady operation since the initial critical attainment in 1964. It has been modified and added many devices in the chance of increasing the reactor power from 1 MW to 5 MW, installing new experimental facilities or fitting to modified nuclear regulations. In order to avoid the unscheduled shutdown of the research reactor by cause the failure of the devices, most of instrumentation system was renewed in 1999. Operating the research reactor more safely and reliably, Supervisory Control Automation and Data Acquisition System which employed personal computers with the Windows NT operating system was added to the conventional instrumentation system, and the fieldbus system called Foundation Fieldbus was installed. Compared with conventional instrumentation system, each fieldbus system has some advantages. Many kinds of fieldbus systems have been developed and sold on the markets in some countries. Foundation Fieldbus standardizing international, which was able to use the devices made by multi-vendor was tentatively installed to study particular techniques about Foundation Fieldbus. The primary coolant flow rate, the temperature difference between the reactor tank inlet and outlet temperatures, the calorimetric power and the reactor power in nuclear instrumentation are monitored on human-machine interface devices on the fieldbus. The programmable logic controller is employed to control the information system for the reactor. This paper introduces Foundation Fieldbus installed. (author)

  12. Think Tank Initiative - Hewlett Foundation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    IDRC and the William and Flora Hewlett Foundation are collaborating on the Think Tank Initiative, a new program to strengthen independent think tanks and policy research centres in the developing world. These organizations provide critical input for the creation of effective public policy to promote growth and reduce ...

  13. Western European Art Foundations and Publishing

    Science.gov (United States)

    King, Lindsay M.; Clement, Russell T.

    2011-01-01

    Western European art foundations create invaluable opportunities for research and exhibition by artists, curators, and scholars. These activities are often documented and disseminated via high-quality publications. This article highlights an important but under-recognized collecting resource for academic and museum libraries by profiling several…

  14. Comprehensive Psychopathological Assessment Based on the Association for Methodology and Documentation in Psychiatry (AMDP) System: Development, Methodological Foundation, Application in Clinical Routine, and Research

    Science.gov (United States)

    Stieglitz, Rolf-Dieter; Haug, Achim; Fähndrich, Erdmann; Rösler, Michael; Trabert, Wolfgang

    2017-01-01

    The documentation of psychopathology is core to the clinical practice of the psychiatrist and clinical psychologist. However, both in initial as well as further training and specialization in their fields, this particular aspect of their work receives scanty attention only. Yet, for the past 50 years, the Association for Methodology and Documentation in Psychiatry (AMDP) System has been in existence and available as a tool to serve precisely the purpose of offering a systematic introduction to the terminology and documentation of psychopathology. The motivation for its development was based on the need for an assessment procedure for the reliable documentation of the effectiveness of newly developed psychopharmacological substances. Subsequently, the AMDP-System began to be applied in the context of investigations into a number of methodological issues in psychiatry (e.g., the frequency and specificity of particular symptoms, the comparison of rating scales). The System then became increasingly important also in clinical practice and, today, represents the most used instrument for the documentation of psychopathology in the German-speaking countries of Europe. This paper intends to offer an overview of the AMDP-System, its origins, design, and functionality. After an initial account of the history and development of the AMDP-System, the discussion will in turn focus on the System’s underlying methodological principles, the transfer of clinical skills and competencies in its practical application, and its use in research and clinical practice. Finally, potential future areas of development in relation to the AMDP-System are explored. PMID:28439242

  15. Governance of Open Source Software Foundations: Who Holds the Power?

    Directory of Open Access Journals (Sweden)

    Ludovico Prattico

    2012-12-01

    Full Text Available The research reported in this article attempts to discover who holds the power in open source software foundations through the analysis of governance documents. Artificial neural network analysis is used to analyse the content of the bylaws of six open source foundations (Apache, Eclipse, GNOME, Plone, Python, and SPI for the purpose of identifying power structures. Results of the research suggest that: i the actions of an open source software foundation are centered around one of three groups: Members, Chairman/President/Executive Director, and Board of Directors; ii in only one of the six foundations is the Board of Directors responsible for both the community and the product; and iii artificial neural network analysis of the content of bylaws provides unbiased insights of the power structure of open source software foundations. These results may prove useful to those who contribute to open source foundations and use their products and services.

  16. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response.

    Science.gov (United States)

    Seo, Ji Yeon; Pyo, Euisun; An, Jin-Pyo; Kim, Jinwoong; Sung, Sang Hyun; Oh, Won Keun

    2017-01-01

    Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata , and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (A β ) 42 -induced microglial activation related to Nrf2 and nuclear factor κ B (NF- κ B)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular A β 42 in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1 β , prostaglandin (PG)E 2 , and nitric oxide (NO) because of artificial phagocytic A β 42 . It decreased pNF- κ B accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits A β 42 -overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

  17. Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Ji Yeon Seo

    2017-01-01

    Full Text Available Therapeutic approach of Alzheimer’s disease (AD has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1/nuclear factor (erythroid-derived 2-like 2 (Nrf2-mediated heme oxygenase (HO-1-inducing effects and the inhibitory activity of amyloid beta (Aβ42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aβ42 in BV-2 cells and decreased the production of interleukin (IL-6, IL-1β, prostaglandin (PGE2, and nitric oxide (NO because of artificial phagocytic Aβ42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS and cyclooxygenase II (COX-II in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aβ42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

  18. History on foundation of Korea nuclear power

    International Nuclear Information System (INIS)

    Park, Ik Su

    1999-12-01

    This reports the history on foundation of Korea nuclear power from 1955 to 1980, which is divided ten chapters. The contents of this book are domestic and foreign affairs before foundation of nuclear power center, establishment of nuclear power and research center, early activity and internal conflict about nuclear power center, study for nuclear power business and commercialization of the studying ordeal over nuclear power administration and new phase, dispute for jurisdiction on nuclear power business and the process, permission for nuclear reactor, regulation and local administration, the process of deliberation and decision of reactor 3. 4 in Yonggwang, introduction of nuclear reprocessing facilities and activities for social organization.

  19. Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet

    International Nuclear Information System (INIS)

    Zhang, Yu-Kun Jennifer; Yeager, Ronnie L.; Tanaka, Yuji; Klaassen, Curtis D.

    2010-01-01

    Oxidative stress has been proposed as an important promoter of the progression of fatty liver diseases. The current study investigates the potential functions of the Nrf2-Keap1 signaling pathway, an important hepatic oxidative stress sensor, in a rodent fatty liver model. Mice with no (Nrf2-null), normal (wild type, WT), and enhanced (Keap1 knockdown, K1-kd) expression of Nrf2 were fed a methionine- and choline-deficient (MCD) diet or a control diet for 5 days. Compared to WT mice, the MCD diet-caused hepatosteatosis was more severe in the Nrf2-null mice and less in the K1-kd mice. The Nrf2-null mice had lower hepatic glutathione and exhibited more lipid peroxidation, whereas the K1-kd mice had the highest amount of glutathione in the liver and developed the least lipid peroxidation among the three genotypes fed the MCD diet. The Nrf2 signaling pathway was activated by the MCD diet, and the Nrf2-targeted cytoprotective genes Nqo1 and Gstα1/2 were induced in WT and even more in K1-kd mice. In addition, Nrf2-null mice on both control and MCD diets exhibited altered expression profiles of fatty acid metabolism genes, indicating Nrf2 may influence lipid metabolism in liver. For example, mRNA levels of long chain fatty acid translocase CD36 and the endocrine hormone Fgf21 were higher in livers of Nrf2-null mice and lower in the K1-kd mice than WT mice fed the MCD diet. Taken together, these observations indicate that Nrf2 could decelerate the onset of fatty livers caused by the MCD diet by increasing hepatic antioxidant and detoxification capabilities.

  20. Lupus Foundation of America

    Science.gov (United States)

    ... Store Read About Our $3.8M Commitment to Stem Cell Research. Learn More Committed to Advancing Research on Lupus ... person with lupus? Get Answers Latest News & Stories Research News | Nov. 16, 2017 Major Lupus Stem Cell Study Receives Funding $3.8 million committed by ...

  1. Foundations of resilience thinking.

    Science.gov (United States)

    Curtin, Charles G; Parker, Jessica P

    2014-08-01

    Through 3 broad and interconnected streams of thought, resilience thinking has influenced the science of ecology and natural resource management by generating new multidisciplinary approaches to environmental problem solving. Resilience science, adaptive management (AM), and ecological policy design (EPD) contributed to an internationally unified paradigm built around the realization that change is inevitable and that science and management must approach the world with this assumption, rather than one of stability. Resilience thinking treats actions as experiments to be learned from, rather than intellectual propositions to be defended or mistakes to be ignored. It asks what is novel and innovative and strives to capture the overall behavior of a system, rather than seeking static, precise outcomes from discrete action steps. Understanding the foundations of resilience thinking is an important building block for developing more holistic and adaptive approaches to conservation. We conducted a comprehensive review of the history of resilience thinking because resilience thinking provides a working context upon which more effective, synergistic, and systems-based conservation action can be taken in light of rapid and unpredictable change. Together, resilience science, AM, and EPD bridge the gaps between systems analysis, ecology, and resource management to provide an interdisciplinary approach to solving wicked problems. © 2014 Society for Conservation Biology.

  2. The logical foundations of mathematics

    CERN Document Server

    Hatcher, William S

    1981-01-01

    The Logical Foundations of Mathematics offers a study of the foundations of mathematics, stressing comparisons between and critical analyses of the major non-constructive foundational systems. The position of constructivism within the spectrum of foundational philosophies is discussed, along with the exact relationship between topos theory and set theory.Comprised of eight chapters, this book begins with an introduction to first-order logic. In particular, two complete systems of axioms and rules for the first-order predicate calculus are given, one for efficiency in proving metatheorems, and

  3. Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

    Directory of Open Access Journals (Sweden)

    Yonggang Wang

    2017-01-01

    Full Text Available Although angiotensin II (Ang II was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN via activating nuclear factor (erythroid-derived 2-like 2 (NRF2, the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2.

  4. The Role of the Nrf2/ARE Antioxidant System in Preventing Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Robert E. Smith

    2016-11-01

    Full Text Available It is widely believed that consuming foods and beverages that have high concentrations of antioxidants can prevent cardiovascular diseases and many types of cancer. As a result, many articles have been published that give the total antioxidant capacities of foods in vitro. However, many antioxidants behave quite differently in vivo. Some of them, such as resveratrol (in red wine and epigallocatechin gallate or EGCG (in green tea can activate the nuclear erythroid-2 like factor-2 (Nrf2 transcription factor. It is a master regulator of endogenous cellular defense mechanisms. Nrf2 controls the expression of many antioxidant and detoxification genes, by binding to antioxidant response elements (AREs that are commonly found in the promoter region of antioxidant (and other genes, and that control expression of those genes. The mechanisms by which Nrf2 relieves oxidative stress and limits cardiac injury as well as the progression to heart failure are described. Also, the ability of statins to induce Nrf2 in the heart, brain, lung, and liver is mentioned. However, there is a negative side of Nrf2. When over-activated, it can cause (not prevent cardiovascular diseases and multi-drug resistance cancer.

  5. Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

    Directory of Open Access Journals (Sweden)

    Angelo Sparaneo

    2016-01-01

    Full Text Available The transcription factor Nrf2 (NF-E2 related factor 2 is a master regulator of the cell antioxidant response associated with tumor growth and resistance to cytotoxic treatments. In particular, Nrf2 induces upregulation of cytoprotective genes by interacting with the closely situated AREs (Antioxidant Response Elements in response to endogenous or exogenous stress stimuli and takes part to several oncogenic signaling pathways. Among these, the crosstalk with Notch pathway has been shown to enhance cytoprotection and maintenance of cellular homeostasis, tissue organization by modulating cell proliferation kinetics, and stem cell self-renewal in several organs. The role of Notch and Nrf2 related pathways in tumorigenesis is highly variable and when they are both abnormally activated they can synergistically cause neoplastic proliferation by promoting cell survival, differentiation, invasion, and metastases. NFE2L2, KEAP1, and NOTCH genes family appear in the list of significantly mutated genes in tumors in both combined and individual sets, supporting the crucial role that the aberrant Nrf2-Notch crosstalk might have in cancerogenesis. In this review, we summarize current knowledge about the alterations of Nrf2 and Notch pathways and their reciprocal transcriptional regulation throughout tumorigenesis and progression of lung tumors, supporting the potentiality of putative biomarkers and therapeutic targets.

  6. Nrf2-peroxiredoxin I axis in polymorphous adenocarcinoma is associated with low matrix metalloproteinase 2 level.

    Science.gov (United States)

    Brod, J M; Demasi, Ana Paula Dias; Montalli, V A; Teixeira, L N; Furuse, C; Aguiar, M C; Soares, A B; Sperandio, M; Araujo, V C

    2017-12-01

    Polymorphous adenocarcinoma (PAC) is a malignant epithelial neoplasm that affects almost exclusively the minor salivary glands, generally described as having a relatively good prognosis. Aberrant nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) activation in tumor cells has been associated with induction of antioxidant enzymes, such as peroxiredoxin I (Prx I) and increased matrix metalloproteinase (MMP) expression. In this context, the aim of the present study was to evaluate the expression of Nrf2 and correlate it with Prx I and MMP-2 secretion in PAC. Thirty-one cases of PAC from oral biopsies were selected and immunohistochemically analyzed for Nrf2 and Prx I. MMP-2 quantification was performed on primary cell cultures derived from PAC. Oral squamous cell carcinoma (OSCC) cell cultures were used as control. A high immunoexpression of Nrf2 was observed in both the cytoplasm and the nucleus of neoplastic cells from PAC. Nuclear staining for Nrf2 suggested its activation in the majority of the PAC cells, which was confirmed by the high expression of its target gene, Prx I. Quantification of MMP-2 secretion showed lower levels in PAC cell cultures when compared to OSCC cell cultures (p high-grade malignancies, such relationship is not infallible and, in fact, the opposite may occur in low-grade tumors, such as PAC of minor salivary glands.

  7. Lansoprazole halts contrast induced nephropathy through activation of Nrf2 pathway in rats.

    Science.gov (United States)

    Khaleel, Sahar A; Alzokaky, Amany A; Raslan, Nahed A; Alwakeel, Asmaa I; Abd El-Aziz, Heba G; Abd-Allah, Adel R

    2017-05-25

    Contrast-induced nephropathy (CIN) is an important cause of acute kidney injury characterized by significant mortality and morbidity. To date, there is no successful protective regimen for CIN especially in poor kidney function patients. Lansoprazole has been shown to exert antioxidant action through induction of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. The aim of the present study is to investigate the potential of lansoprazole to activate Nrf2 pathway in the kidney and consequently to protect against oxidative stress induced by iodinated contrast media. Lansoprazole, at a dose of 100 mg/kg, showed a significant induction of Nrf2 mRNA after 3 h. Administration of contrast media induced significant increase in serum creatinine and blood urea nitrogen, histological deterioration, and reduction in total antioxidant capacity. Moreover, it instigated the defensive Nrf2 gene expression and immunoreactivity. In addition, there were overexpression of HO-1, caspase 3, p53 and IL6 genes and downregulation of Bcl2 gene. Pre-treatment with lansoprazole (100 mg/kg) ameliorated the nephrotoxicity parameters and oxidative stress, improved histological lesions, and hijacked apoptotic and inflammatory markers that were provoked by contrast media. In conclusion, lansoprazole attenuates experimental CIN which might be due to activation of Nrf2 antioxidant defence pathway. These findings highlight the potential benefit of incorporating lansoprazole in the protective regimen against CIN especially for susceptible patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality?

    Science.gov (United States)

    Houghton, Christine A.; Fassett, Robert G.; Coombes, Jeff S.

    2016-01-01

    The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements. PMID:26881038

  9. Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

    Energy Technology Data Exchange (ETDEWEB)

    Ohnuma, Tomokazu; Matsumoto, Takashi; Itoi, Ayano; Kawana, Ayako; Nishiyama, Takahito; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira, E-mail: hiratuka@toyaku.ac.jp [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)

    2011-10-07

    Highlights: {yields} We found a novel inhibitor of Nrf2 known as a chemoresistance factor. {yields} Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. {yields} Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. {yields} Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

  10. The nuclear factor (erythroid-derived 2)-like 2 (NRF2) antioxidant response promotes melanocyte viability and reduces toxicity of the vitiligo-inducing phenol monobenzone.

    Science.gov (United States)

    Arowojolu, Omotayo A; Orlow, Seth J; Elbuluk, Nada; Manga, Prashiela

    2017-07-01

    Vitiligo, characterised by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterised. We hypothesised that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Mortality of people with chronic fatigue syndrome: a retrospective cohort study in England and Wales from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) Register.

    Science.gov (United States)

    Roberts, Emmert; Wessely, Simon; Chalder, Trudie; Chang, Chin-Kuo; Hotopf, Matthew

    2016-04-16

    Mortality associated with chronic fatigue syndrome is uncertain. We investigated mortality in individuals diagnosed with chronic fatigue syndrome in secondary and tertiary care using data from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Clinical Record Interactive Search (CRIS) register. We calculated standardised mortality ratios (SMRs) for all-cause, suicide-specific, and cancer-specific mortality for a 7-year observation period using the number of deaths observed in SLaM records compared with age-specific and sex-specific mortality statistics for England and Wales. Study participants were included if they had had contact with the chronic fatigue service (referral, discharge, or case note entry) and received a diagnosis of chronic fatigue syndrome. We identified 2147 cases of chronic fatigue syndrome from CRIS and 17 deaths from Jan 1, 2007, to Dec 31, 2013. 1533 patients were women of whom 11 died, and 614 were men of whom six died. There was no significant difference in age-standardised and sex-standardised mortality ratios (SMRs) for all-cause mortality (SMR 1·14, 95% CI 0·65-1·85; p=0·67) or cancer-specific mortality (1·39, 0·60-2·73; p=0·45) in patients with chronic fatigue syndrome when compared with the general population in England and Wales. This remained the case when deaths from suicide were removed from the analysis. There was a significant increase in suicide-specific mortality (SMR 6·85, 95% CI 2·22-15·98; p=0·002). We did not note increased all-cause mortality in people with chronic fatigue syndrome, but our findings show a substantial increase in mortality from suicide. This highlights the need for clinicians to be aware of the increased risk of completed suicide and to assess suicidality adequately in patients with chronic fatigue syndrome. National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

  12. Keap1/Nrf2 pathway in kidney cancer : frequent methylation of KEAP1 gene promoter in clear renal cell carcinoma

    NARCIS (Netherlands)

    Fabrizio, Federico Pio; Costantini, Manuela; Copetti, Massimiliano; la Torre, Annamaria; Sparaneo, Angelo; Fontana, Andrea; Poeta, Luana; Gallucci, Michele; Sentinelli, Steno; Graziano, Paolo; Parente, Paola; Pompeo, Vincenzo; De Salvo, Laura; Simone, Giuseppe; Papalia, Rocco; Picardo, Francesco; Balsamo, Teresa; Flammia, Gerardo Paolo; Trombetta, Domenico; Pantalone, Angela; Kok, Klaas; Paranita, Ferronika; Muscarella, Lucia Anna; Fazio, Vito Michele

    2017-01-01

    The Keap1/Nrf2 pathway is a master regulator of the cellular redox state through the induction of several antioxidant defence genes implicated in chemotherapeutic drugs resistance of tumor cells. An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal

  13. The Foundations of Radiation Belt Research

    Science.gov (United States)

    Ludwig, G. H.

    2008-12-01

    The United States undertook the launching of an artificial Earth satellite as part of its contribution to the International Geophysical Year. The Vanguard program was established to meet that commitment, and it developed a launch vehicle, ground station network, and suite of scientific payloads, including the cosmic ray experiment proposed by James A. Van Allen. Although Vanguard eventually exceeded all of its pre-stated goals, the preemptive launches of Sputniks I and II by the Soviets in October and November 1957 spurred the U.S. into a frenzy of activity, resulting in the launches of Explorers I and III in January and March of 1958. The data from those two satellites quickly revealed the lower boundary of an unexpected region of high intensity radiation trapped in the Earth's magnetic field. The original announcement in May 1958 stated that the radiation was probably composed of either protons or electrons, and that, if electrons, it was probably bremsstrahlung formed in the satellite shell. Immediately following that announcement, approval was received for what became Explorer IV, whose announced purpose was to follow up on the new discovery. Another reason for the satellite, unmentioned at the time, was its inclusion as a component of the highly classified Argos program, a covert military program to test whether the detonation of nuclear devices at high altitude would inject measurable numbers of charged particles into durable trajectories in the Earth's magnetic field. Our team at Iowa produced the satellites under the oversight of, and with assistance by, the Army Ballistic Missile Agency in Huntsville, and with the contributions of key hardware from several other government laboratories. The project was completed in the unbelievably short period of seventy-seven days from approval to launch. Launched into a higher-inclination orbit than the earlier Explorers, Explorer IV confirmed the discovery and greatly expanded our understanding of the natural phenomenon. It also provided the first hint that there were two distinct radiation belts, although that conclusion was not reached until later. Although that new information was quickly announced, the results of the high altitude nuclear detonations were kept secret until well into 1959. They clearly revealed the charged particle shells created by the Argos nuclear detonations. The next major step in mapping and understanding the high-intensity radiation involved the launch of deep space probes Pioneers III and IV in December 1958 and March 1959. Although both launches fell short in their primary objective, to reach the moon, they traveled far enough from the Earth to fully meet the needs of the scientific experiment. They very clearly showed the two-radiation belt structure, and mapped its extent. They also showed the probable effect of a magnetic storm on 25 February, thus indicating the direct influence of solar activity on the outer belt. By the end of 1959, the existence of the Van Allen Radiation Belts and their general structure were solidly established, early information about the composition of the radiation was appearing in print, and energetic work was under way to understand the physics of the processes involved.

  14. Fisher Center for Alzheimer's Research Foundation

    Science.gov (United States)

    ... Hear Kent Karosen, President and CEO of the Fisher Center, describe his new book and the power ... Signs of Alzheimer's Clinical Stages of Alzheimer’s About Fisher About Us Board of Trustees Financials Terms of ...

  15. Research award: Foundations for Innovation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-09-06

    Sep 6, 2017 ... academic/non-academic partnerships in support of social or economic ... for scaling-up new, development-oriented technologies in LMICs. ... for this position, and explain how this opportunity will advance their career goals.

  16. MS Swaminathan Research Foundation : Organizational and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Le CRDI lance un nouveau projet dans la région de l'ANASE. L'honorable Chrystia Freeland, ministre du Commerce international, a annoncé le lancement d'un nouveau projet financé par le Centre de recherches pour le développement international (CRDI). Voir davantageLe CRDI lance un nouveau projet dans la région ...

  17. Michael J. Fox Foundation for Parkinson's Research

    Science.gov (United States)

    ... Tribute Gift Send an Ecard Team Fox Donation Employer Matching Gifts Planned Giving Other Ways to Give ... Fox Trial Finder Italy | Fox Shop | FAQs | Careers | Leadership & Staff | Contact Us | Español Facebook Twitter YouTube Instagram ...

  18. Western Kentucky University Research Foundation Biodiesel Project

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Wei-Ping [Principal Investigator; Cao, Yan [Co-Principal Investigator

    2013-03-15

    Petroleum-based liquid hydrocarbons is exclusively major energy source in the transportation sector. Thus, it is the major CO{sub 2} source which is the associated with greenhouse effect. In the United States alone, petroleum consumption in the transportation sector approaches 13.8 million barrels per day (Mbbl/d). It is corresponding to a release of 0.53 gigatons of carbon per year (GtC/yr), which accounts for approximate 7.6 % of the current global release of CO{sub 2} from all of the fossil fuel usage (7 GtC/yr). For the long term, the conventional petroleum production is predicted to peak in as little as the next 10 years to as high as the next 50 years. Negative environmental consequences, the frequently roaring petroleum prices, increasing petroleum utilization and concerns about competitive supplies of petroleum have driven dramatic interest in producing alternative transportation fuels, such as electricity-based, hydrogen-based and bio-based transportation alternative fuels. Use of either of electricity-based or hydrogen-based alternative energy in the transportation sector is currently laden with technical and economical challenges. The current energy density of commercial batteries is 175 Wh/kg of battery. At a storage pressure of 680 atm, the lower heating value (LHV) of H{sub 2} is 1.32 kWh/liter. In contrast, the corresponding energy density for gasoline can reach as high as 8.88 kWh/liter. Furthermore, the convenience of using a liquid hydrocarbon fuel through the existing infrastructures is a big deterrent to replacement by both batteries and hydrogen. Biomass-derived ethanol and bio-diesel (biofuels) can be two promising and predominant U.S. alternative transportation fuels. Both their energy densities and physical properties are comparable to their relatives of petroleum-based gasoline and diesel, however, biofuels are significantly environmental-benign. Ethanol can be made from the sugar-based or starch-based biomass materials, which is easily fermented to create ethanol. In the United States almost all starch ethanol is mainly manufactured from corn grains. The technology for manufacturing corn ethanol can be considered mature as of the late 1980s. In 2005, 14.3 % of the U.S. corn harvest was processed to produce 1.48 x10{sup 10} liters of ethanol, energetically equivalent to 1.72 % of U.S. gasoline usage. Soybean oil is extracted from 1.5 % of the U.S. soybean harvest to produce 2.56 x 10{sup 8} liters of bio-diesel, which was 0.09 % of U.S. diesel usage. However, reaching maximum rates of bio-fuel supply from corn and soybeans is unlikely because these crops are presently major contributors to human food supplies through livestock feed and direct consumption. Moreover, there currently arguments on that the conversion of many types of many natural landscapes to grow corn for feedstock is likely to create substantial carbon emissions that will exacerbate globe warming. On the other hand, there is a large underutilized resource of cellulose biomass from trees, grasses, and nonedible parts of crops that could serve as a feedstock. One of the potentially significant new bio-fuels is so called "cellulosic ethanol", which is dependent on break-down by microbes or enzymes. Because of technological limitations (the wider variety of molecular structures in cellulose and hemicellulose requires a wider variety of microorganisms to break them down) and other cost hurdles (such as lower kinetics), cellulosic ethanol can currently remain in lab scales. Considering farm yields, commodity and fuel prices, farm energy and agrichemical inputs, production plant efficiencies, byproduct production, greenhouse gas (GHG) emissions, and other environmental effects, a life-cycle evaluation of competitive indicated that corn ethanol yields 25 % more energy than the energy invested in its production, whereas soybean bio-diesel yields 93 % more. Relative to the fossil fuels they displace, greenhouse gas emissions are reduced 12 % by the production and combustion of ethanol and 41 % by bio-diesel. Bio-diesel also releases less air pollutants per net energy gain than ethanol. Bio-diesel has advantages over ethanol due to its lower agricultural inputs and more efficient conversion. Thus, to be a viable alternative, a bio-fuel firstly should be producible in large quantities without reducing food supplies. In this aspect, larger quantity supplies of cellulose biomass are likely viable alternatives. U. S. Congress has introduced an initiative and subsequently rolled into the basic energy package, which encourages the production of fuel from purely renewable resources, biomass. Secondly, a bio-fuel should also provide a net energy gain, have environmental benefits and be economically competitive. In this aspect, bio-diesel has advantages over ethanol. The commonwealth of Kentucky is fortunate to have a diverse and abundant supply of renewable energy resources. Both Kentucky Governor Beshear in the energy plan for Kentucky "Intelligent Energy Choices for Kentucky's Future", and Kentucky Renewable Energy Consortium, outlined strategies on developing energy in renewable, sustainable and efficient ways. Smart utilization of diversified renewable energy resources using advanced technologies developed by Kentucky public universities, and promotion of these technologies to the market place by collaboration between universities and private industry, are specially encouraged. Thus, the initially question answering Governor's strategic plan is if there is any economical way to make utilization of larger quantities of cellulose and hemicellulose for production of bio-fuels, especially bio-diesel. There are some possible options of commercially available technologies to convert cellulose based biomass energy to bio-fuels. Cellulose based biomass can be firstly gasified to obtain synthesis gas (a mixture of CO and H{sub 2}), which is followed up by being converted into liquid hydrocarbon fuels or oxygenate hydrocarbon fuel through Fischer-Tropsch (F-T) synthesis. Methanol production is regarded to be the most economic starting step in many-year practices of the development of F-T synthesis technology since only C{sub 1} synthesis through F-T process can potentially achieve 100% conversion efficiency. Mobil's F-T synthesis process is based on this understanding. Considering the economical advantages of bio-diesel production over ethanol and necessary supply of methanol during bio-diesel production, a new opportunity for bio-diesel production with total supplies of biomass-based raw materials through more economic reaction pathways is likely identified in this proposal. The bio-oil part of biomass can be transesterified under available methanol (or mixed alcohols), which can be synthesized in the most easy part of F-T synthesis process using synthesis gas from gasification of cellulose fractions of biomass. We propose a novel concept to make sense of bio-diesel production economically though a coupling reaction of bio-oil transesterification and methanol synthesis. It will overcome problems of current bio-diesel producing process based on separated handling of methanol and bio-oil.

  19. Theoretical Foundation for Advanced Distributed Learning Research

    National Research Council Canada - National Science Library

    Hays, Robert

    2001-01-01

    ... and constrained by system principles. The goal of this paper is to sensitize individuals working in all aspects of ADL systems to the power of a system view and to provide several examples of system methods...

  20. Antithetic Foundations of Economics

    Directory of Open Access Journals (Sweden)

    Marin Dinu

    2011-03-01

    Full Text Available This paper aims at decrypting the manner in which the foundations of Economics as a science and the meanings of the relevant explanatory formulas are being shaped. My analytical endeavor focuses on understanding the peculiarities of what is referred to as the object of study of the science known as Economics, an academic synthesis of concept-related breakthroughs regarding economicity. The explicit purpose of this analysis is to identify perennial benchmarks in economic cognition whereby this ensures its consistency. The implicit purpose is to shape a cognitive model in line with the specifics of the conceptual universe of Economics, as well as with the sources of the economic realities that are subject to a sui-generis relativism. The primary benefit of this endeavor consists in systemizing the conceptual prospects with an antithetic nature that allow for the explanations of the state of economic rationality and generate the understanding of what the source of economicity is and how it behaves. As such, the conclusions are marked by the stringent need of more precisely defining economic knowledge in order to match the changing nature of economic reality, as an expression that embraces the meeting point of two ontological vistas that are methodologically separated by some theories: human nature and human condition. Economics as a science thus features, apart from a conceptual substrate that needs to be spotted, an ontological background that needs to be revealed. The role played by this background appears to be most frequently ignored. The joint identification of both direct and contextual determinants for a sensitive area of humankind, i.e. the economy, is a direction to be followed by the royal path of rational knowledge.

  1. Curcumin Derivative Epigenetically Reactivates Nrf2 Antioxidative Stress Signaling in Mouse Prostate Cancer TRAMP C1 Cells.

    Science.gov (United States)

    Li, Wenji; Su, Zheng-Yuan; Guo, Yue; Zhang, Chengyue; Wu, Renyi; Gao, Linbo; Zheng, Xi; Du, Zhi-Yun; Zhang, Kun; Kong, Ah-Ng

    2018-02-19

    The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-bis-(3,4,5-trimethoxybenzylidene)-tetrahydro-thiopyran-4-one (F10) and (3E,5E)-3,5-bis-(3,4,5-trimethoxy-benzylidene)-tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin, and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways. We performed real-time quantitative PCR and Western blotting to investigate the effects of F10 and E10 on Nrf2, correlated phase II detoxification genes. We also measured expression and activity of DNMTand HDAC enzymes. Enrichment of H3K27me3 on the promoter region of Nrf2 was explored with a chromatin immunoprecipitation (ChIP) assay. Methylation of the CpG region in Nrf2 promoter was doubly examined by bisulfite genomic sequencing (BGS) and methylation DNA immunoprecipitation (MeDIP). Compared with curcumin and SFN, F10 is more potent in activating Nrf2-ARE pathways. Both F10 and E10 enhanced level of Nrf2 and the correlated phase II detoxifying genes. BGS and MeDIP assays indicated that F10 but not E10 hypomethylated the Nrf2 promoter. F10 also downregulated the protein level of DNMT1, DNMT3a, DNMT3b, HDAC1, HDAC4, and HDAC7 and the activity of DNMTs and HDACs. F10 but not E10 effectively reduced the accumulation of H3k27me3 on the promoter of Nrf2. F10 and E10 can activate the Nrf2-ARE pathway and increase the level of Nrf2 and correlated phase II detoxification genes. The reactivation effect on Nrf2 by F10 in TRAMP C1 may come from demethylation, decrease of HDACs, and inhibition of H3k27me3 accumulation.

  2. Evaluating the philosophical foundation of 2013 Curriculum

    Directory of Open Access Journals (Sweden)

    M. Mardiana

    2017-12-01

    Full Text Available The study was to: (1 identify the interpretation toward the philosophical foundation of 2013 Curriculum; and (2 evaluate the philosophical foundation of 2013 Curriculum. In order to achieve these objectives, the researchers implemented the method of philosophy interpretation, namely a method that might discover an individual’s paradigm through the texts or the articles that he or she composed. Furthermore, in order to evaluate the philosophical foundation of 2013 Curriculum the researchers implemented certain criteria and this effort was supported by the expert interview. The data were analyzed by means of hermeneutic method, namely the presence of a relationship among the three elements namely text, interpreter and reader. The conclusions of the study then were as follows: (1 the interpretation toward the philosophical foundation of 2013 Curriculum contained six points namely: (a establishing and developing the nation’s attitude and civilization or the nation’s character, (b developing the curriculum based on the nation’s culture, (c referring to the fact that education had been a process of developing the learning participants’ potentials, (d referring to the fact that education had been based on the nation’s culture and experience in the past, (e referring to the fact that education had been basis of the nation’s life continuity and (f Referring to the fact that education had been adjusted to the life of the learning participants as an individual, a society member and a citizen; (2 the six philosophical reasons namely: (a perennialism, (b essentialism, (c progressivism, (d pragmatism, (e existentialism and (f reconstructionism; (3 the following evaluation results: (a the philosophical foundation of 2013 Curriculum based on the interpretation results had provided clear educational objectives and functions, (b the philosophical foundation of 2013 Curriculum had been in accordance to facts, (c the philosophical foundation of 2013

  3. Theodore Presser and His Foundation.

    Science.gov (United States)

    Nazzaro, William J.

    1983-01-01

    Describes the life of Theodore Presser and the establishment of the Presser Foundation in 1916. Presser was a music publisher and the founder of "Etude" magazine. The Presser Foundation provides scholarships to music students, aid to elderly music teachers, and help to colleges for building music facilities. (CS)

  4. Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.

    Science.gov (United States)

    Mascuch, Samantha J; Boudreau, Paul D; Carland, Tristan M; Pierce, N Tessa; Olson, Joshua; Hensler, Mary E; Choi, Hyukjae; Campanale, Joseph; Hamdoun, Amro; Nizet, Victor; Gerwick, William H; Gaasterland, Teresa; Gerwick, Lena

    2018-03-23

    The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keap1. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.

  5. Clearinghouse Goes beyond Foundation Walls to Link Youth Programs.

    Science.gov (United States)

    Quill and Scroll, 1997

    1997-01-01

    Recounts how the Newspaper Association of America Foundation is setting up a clearinghouse to conduct research with those to be served (young people), is designing a site, and is implementing the project. States that the Foundation sent questionnaires to leaders in youth service areas asking for 13 different kinds of information and that response…

  6. The William and Flora Hewlett Foundation | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    The William and Flora Hewlett Foundation. The William and Flora Hewlett Foundation. http://www.hewlett.org/. Think Tank Initiative. This initiative is creating high-quality independent research and policy institutions throughout the developing world. View more. Think Tank Initiative. Growth and Economic Opportunities for ...

  7. Foundation Degree Learning: An Educational Journey of Personal Development

    Science.gov (United States)

    Herrera, Helena; Brown, David; Portlock, Jane

    2015-01-01

    The foundation degree is an intermediate-level qualification designed to widen participation in higher education while providing work-related skills and knowledge. It has a vocational focus and a pedagogic approach that integrates academic and work-based learning. Research into opportunities and the process of learning within foundation degrees is…

  8. Quantum theory informational foundations and foils

    CERN Document Server

    Spekkens, Robert

    2016-01-01

    This book provides the first unified overview of the burgeoning research area at the interface between Quantum Foundations and Quantum Information.  Topics include: operational alternatives to quantum theory, information-theoretic reconstructions of the quantum formalism, mathematical frameworks for operational theories, and device-independent features of the set of quantum correlations. Powered by the injection of fresh ideas from the field of Quantum Information and Computation, the foundations of Quantum Mechanics are in the midst of a renaissance. The last two decades have seen an explosion of new results and research directions, attracting broad interest in the scientific community. The variety and number of different approaches, however, makes it challenging for a newcomer to obtain a big picture of the field and of its high-level goals. Here, fourteen original contributions from leading experts in the field cover some of the most promising research directions that have emerged in the new wave of quant...

  9. Can Innate, modular "foundations" explain morality? Challenges for Haidt's Moral Foundations Theory.

    Science.gov (United States)

    Suhler, Christopher L; Churchland, Patricia

    2011-09-01

    Jonathan Haidt's Moral Foundations Theory is an influential scientific account of morality incorporating psychological, developmental, and evolutionary perspectives. The theory proposes that morality is built upon five innate "foundations," each of which is believed to have been selected for during human evolution and, subsequently, tuned-up by learning during development. We argue here that although some general elements of Haidt's theory are plausible, many other important aspects of his account are seriously flawed. First, innateness and modularity figure centrally in Haidt's account, but terminological and conceptual problems foster confusion and ambiguities. Second, both the theory's proposed number of moral foundations and its taxonomy of the moral domain appear contrived, ignoring equally good candidate foundations and the possibility of substantial intergroup differences in the foundations' contents. Third, the mechanisms (viz., modules) and categorical distinctions (viz., between foundations) proposed by the theory are not consilient with discoveries in contemporary neuroscience concerning the organization, functioning, and development of the brain. In light of these difficulties, we suggest that Haidt's theory is inadequate as a scientific account of morality. Nevertheless, the theory's weaknesses are instructive, and hence, criticism may be useful to psychologists, neuroscientists, and philosophers attempting to advance theories of morality, as well as to researchers wishing to invoke concepts such as innateness and modularity more generally.

  10. Dendritic cells' death induced by contact sensitizers is controlled by Nrf2 and depends on glutathione levels

    Energy Technology Data Exchange (ETDEWEB)

    El Ali, Zeina [UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry (France); Deloménie, Claudine [IFR141 IPSIT, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry (France); Botton, Jérémie [INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Team (France); Pallardy, Marc [UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry (France); Kerdine-Römer, Saadia, E-mail: saadia.kerdine-romer@u-psud.fr [UMR996 - Inflammation, Chemokines and Immunopathology-, INSERM, Univ Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry (France)

    2017-05-01

    Dendritic cells (DC) are known to play a major role during contact allergy induced by contact sensitizers (CS). Our previous studies showed that Nrf2 was induced in DC and controlled allergic skin inflammation in mice in response to chemicals. In this work, we raised the question of the role of Nrf2 in response to a stress provoked by chemical sensitizers in DC. We used two well-described chemical sensitizers, dinitrochlorobenzene (DNCB) and cinnamaldehyde (CinA), known to have different chemical reactivity and mechanism of action. First, we performed a RT-qPCR array showing that CinA was a higher inducer of immune and detoxification genes compared to DNCB. Interestingly, in the absence of Nrf2, gene expression was dramatically affected in response to DNCB but was slightly affected in response to CinA. These observations prompted us to study DC's cell death in response to both chemicals. DNCB and CinA increased apoptotic cells and decreased living cells in the absence of Nrf2. The characterization of DC apoptosis induced by both CS involved the mitochondrial-dependent caspase pathway and was regulated via Nrf2 in response to both chemicals. Oxidative stress induced by DNCB, and leading to cell death, was regulated by Nrf2. Unlike CinA, DNCB treatment provoked a significant reduction of intracellular GSH levels and up-regulated bcl-2 gene expression, under the control of Nrf2. This work underlies that chemical reactivity may control Nrf2-dependent gene expression leading to different cytoprotective mechanisms in DC. - Highlights: • Nrf2 controls cell death induced by contact sensitizers in dendritic cells. • DNCB reduced GSH levels and up-regulated bcl-2 gene expression unlike CinA. • Chemical reactivity controls Nrf2-dependent genes having protective effect in DC.

  11. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

    Science.gov (United States)

    Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-01-01

    Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

  12. Escin activates AKT-Nrf2 signaling to protect retinal pigment epithelium cells from oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kaijun [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China); Jiang, Yiqian [The First People Hospital of Xiaoshan, Hangzhou (China); Wang, Wei; Ma, Jian [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China); Chen, Min, E-mail: eyedrchenminzj@163.com [Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou (China); Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou (China)

    2015-12-25

    Here we explored the anti-oxidative and cytoprotective potentials of escin, a natural triterpene-saponin, against hydrogen peroxide (H{sub 2}O{sub 2}) in retinal pigment epithelium (RPE) cells. We showed that escin remarkably attenuated H{sub 2}O{sub 2}-induced death and apoptosis of established (ARPE-19) and primary murine RPE cells. Meanwhile, ROS production and lipid peroxidation by H{sub 2}O{sub 2} were remarkably inhibited by escin. Escin treatment in RPE cells resulted in NF-E2-related factor 2 (Nrf2) signaling activation, evidenced by transcription of anti-oxidant-responsive element (ARE)-regulated genes, including HO-1, NQO-1 and SRXN-1. Knockdown of Nrf2 through targeted shRNAs/siRNAs alleviated escin-mediated ARE gene transcription, and almost abolished escin-mediated anti-oxidant activity and RPE cytoprotection against H{sub 2}O{sub 2}. Reversely, escin was more potent against H{sub 2}O{sub 2} damages in Nrf2-over-expressed ARPE-19 cells. Further studies showed that escin-induced Nrf2 activation in RPE cells required AKT signaling. AKT inhibitors (LY294002 and perifosine) blocked escin-induced AKT activation, and dramatically inhibited Nrf2 phosphorylation, its cytosol accumulation and nuclear translocation in RPE cells. Escin-induced RPE cytoprotection against H{sub 2}O{sub 2} was also alleviated by the AKT inhibitors. Together, these results demonstrate that escin protects RPE cells from oxidative stress possibly through activating AKT-Nrf2 signaling.

  13. Effects of trigonelline inhibition of the Nrf2 transcription factor in vitro on Echinococcus granulosus.

    Science.gov (United States)

    Qin, Wenjuan; Guan, Dongfang; Ma, Rongji; Yang, Rentan; Xing, Guoqiang; Shi, Hongjuan; Tang, Guangyao; Li, Jiajie; Lv, Hailong; Jiang, Yufeng

    2017-08-01

    The aim of this study was to investigate the impact of trigonelline (TRG) on Echinococcus granulosus, and to explore the inhibition impact of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway on E. granulosus protoscoleces. Echinococcus granulosus protoscoleces were incubated with various concentrations of TRG, and then Nrf2 protein expression and its localization in protoscoleces were detected by western blot analysis and immunofluorescence assay, respectively. Reactive oxygen species (ROS) level in protoscoleces was measured using ROS detection kit. Caspase-3 activity was measured using a caspase-3 activity assay kit, and NAD(P)H quinone oxidoreductase (NQO)-1 and heme oxygenase (HO)-1 activities in protoscoleces were measured by ELISA. The effect of TRG on protoscoleces viability was investigated using 0.1% eosin staining, and ultrastructural alterations in protoscoleces were examined by scanning electron microscopy (SEM). Immunolocalization experiment clearly showed that Nrf2 protein was predominantly present in cells of protoscoleces. TRG treatment reduced NQO-1 and HO-1 activities in protoscoleces, but could increase ROS level at early time. Protoscoleces could not survive when treated with 250 μM TRG for 12 days. SEM results showed that TRG-treated protoscoleces presented damage in the protoscoleces region, including hook deformation, lesions, and digitiform protuberance. Nrf2 protein expression was significantly decreased and caspase-3 activity was clearly increased in protoscoleces treated with TRG for 24 and 48 h, respectively, when compared with that in controls (P granulosus protoscoleces. Nrf2 protein was mainly expressed in the cells and TRG could efficiently inhibit the Nrf2 signaling pathway in E. granulosus. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For

  14. Pharmacological targeting of GSK-3 and NRF2 provides neuroprotection in a preclinical model of tauopathy

    Directory of Open Access Journals (Sweden)

    Antonio Cuadrado

    2018-04-01

    Full Text Available Tauopathies are a group of neurodegenerative disorders where TAU protein is presented as aggregates or is abnormally phosphorylated, leading to alterations of axonal transport, neuronal death and neuroinflammation. Currently, there is no treatment to slow progression of these diseases. Here, we have investigated whether dimethyl fumarate (DMF, an inducer of the transcription factor NRF2, could mitigate tauopathy in a mouse model. The signaling pathways modulated by DMF were also studied in mouse embryonic fibroblast (MEFs from wild type or KEAP1-deficient mice. The effect of DMF on neurodegeneration, astrocyte and microglial activation was examined in Nrf2+/+ and Nrf2−/− mice stereotaxically injected in the right hippocampus with an adeno-associated vector expressing human TAUP301L and treated daily with DMF (100 mg/kg, i.g during three weeks. DMF induces the NRF2 transcriptional through a mechanism that involves KEAP1 but also PI3K/AKT/GSK-3-dependent pathways. DMF modulates GSK-3β activity in mouse hippocampi. Furthermore, DMF modulates TAU phosphorylation, neuronal impairment measured by calbindin-D28K and BDNF expression, and inflammatory processes involved in astrogliosis, microgliosis and pro-inflammatory cytokines production. This study reveals neuroprotective effects of DMF beyond disruption of the KEAP1/NRF2 axis by inhibiting GSK3 in a mouse model of tauopathy. Our results support repurposing of this drug for treatment of these diseases. Keywords: DMF, Inflammation, Neurodegeneration, NRF2, Oxidative stress, TAU/ GSK-3

  15. Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms

    Directory of Open Access Journals (Sweden)

    Chang Joo Oh

    2014-01-01

    Full Text Available Excessive proliferation of vascular smooth muscle cells (VSMCs and incomplete re-endothelialization is a major clinical problem limiting the long-term efficacy of percutaneous coronary angioplasty. We tested if dimethylfumarate (DMF, an anti-psoriasis drug, could inhibit abnormal vascular remodeling via NF−E2-related factor 2 (Nrf2-NAD(PH quinone oxidoreductase 1 (NQO1 activity. DMF significantly attenuated neointimal hyperplasia induced by balloon injury in rat carotid arteries via suppression of the G1 to S phase transition resulting from induction of p21 protein in VSMCs. Initially, DMF increased p21 protein stability through an enhancement in Nrf2 activity without an increase in p21 mRNA. Later on, DMF stimulated p21 mRNA expression through a process dependent on p53 activity. However, heme oxygenase-1 (HO-1 or NQO1 activity, well-known target genes induced by Nrf2, were dispensable for the DMF induction of p21 protein and the effect on the VSMC proliferation. Likewise, DMF protected endothelial cells from TNF-α-induced apoptosis and the dysfunction characterized by decreased eNOS expression. With knock-down of Nrf2 or NQO1, DMF failed to prevent TNF-α-induced cell apoptosis and decreased eNOS expression. Also, CD31 expression, an endothelial specific marker, was restored in vivo by DMF. In conclusion, DMF prevented abnormal proliferation in VSMCs by G1 cell cycle arrest via p21 upregulation driven by Nrf2 and p53 activity, and had a beneficial effect on TNF-α-induced apoptosis and dysfunction in endothelial cells through Nrf2–NQO1 activity suggesting that DMF might be a therapeutic drug for patients with vascular disease.

  16. Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yanli Liu

    2017-05-01

    Full Text Available The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. We used real-time PCR, Western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the function of nuclear factor-erythroid 2-related factor 2 (Nrf2. We demonstrated that with upregulated levels of reactive oxygen species (ROS and malondialdehyde (MDA, the effect of oxidative stress was obvious under H2O2 treatment. Oxidative molecules were altered after the H2O2 exposure, whereby the signaling of Nrf2 was activated with an increase in its downstream effectors, heme oxygenase-1 (HO-1, NAD(PH:quinone oxidoreductase 1 (NQO1 and γ-glutamyl cysteine synthetase (γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress by the upregulation of caspase-9, caspase-3, Bax and c-Fos levels in addition to the downregulation of Bcl-2. However, there was no alterations in levels of caspase-8. The enhanced antioxidant effect could not mitigate the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, Bax and c-Fos, but not that of caspase-8. In contrast, silencing the expression of Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on regulating oxidative stress and anti-intrinsic apoptosis by the activation of oxidative enzymes.

  17. Licochalcone A Upregulates Nrf2 Antioxidant Pathway and Thereby Alleviates Acetaminophen-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hongming Lv

    2018-03-01

    Full Text Available Acetaminophen (APAP overdose-induced fatal hepatotoxicity is majorly characterized by overwhelmingly increased oxidative stress while enhanced nuclear factor-erythroid 2-related factor 2 (Nrf2 is involved in prevention of hepatotoxicity. Although Licochalcone A (Lico A upregulates Nrf2 signaling pathway against oxidative stress-triggered cell injury, whether it could protect from APAP-induced hepatotoxicity by directly inducing Nrf2 activation is still poorly elucidated. This study aims to explore the protective effect of Lico A against APAP-induced hepatotoxicity and its underlying molecular mechanisms. Our findings indicated that Lico A effectively decreased tert-butyl hydroperoxide (t-BHP- and APAP-stimulated cell apoptosis, mitochondrial dysfunction and reactive oxygen species generation and increased various anti-oxidative enzymes expression, which is largely dependent on upregulating Nrf2 nuclear translocation, reducing the Keap1 protein expression, and strengthening the antioxidant response element promoter activity. Meanwhile, Lico A dramatically protected against APAP-induced acute liver failure by lessening the lethality; alleviating histopathological liver changes; decreasing the alanine transaminase and aspartate aminotransferase levels, malondialdehyde formation, myeloperoxidase level and superoxide dismutase depletion, and increasing the GSH-to-GSSG ratio. Furthermore, Lico A not only significantly modulated apoptosis-related protein by increasing Bcl-2 expression, and decreasing Bax and caspase-3 cleavage expression, but also efficiently alleviated mitochondrial dysfunction by reducing c-jun N-terminal kinase phosphorylation and translocation, inhibiting Bax mitochondrial translocation, apoptosis-inducing factor and cytochrome c release. However, Lico A-inhibited APAP-induced the lethality, histopathological changes, hepatic apoptosis, and mitochondrial dysfunction in WT mice were evidently abrogated in Nrf2-/- mice. These

  18. Proteus Syndrome Foundation

    Science.gov (United States)

    ... Syndrome Diagnostic Criteria & FAQs Medical Research Glossary Donate Cash Donation Life Insurance Gift Matching Gift Stock Gift ... data It’s easy to join There is no cost to you: the costs are supported by the ...

  19. Foundations of health psychology

    National Research Council Canada - National Science Library

    Friedman, Howard S; Silver, Roxane Cohen

    2007-01-01

    ... and Effective Treatment 9 Adjustment to Chronic Disease: Progress and Promise in Research Annette L. Stanton and Tracey A. Revenson 203 10 Aging and Health 234 Karen S. Rook, Susan T. Charles, and...

  20. Genetic Disease Foundation

    Science.gov (United States)

    ... has used its fundraising efforts to help further research programs at Mount Sinai. Spotlight: Gaucher Gaucher Disease is the most common of the lipid storage diseases. Learn about its symptoms, how it ...