WorldWideScience

Sample records for sustainability proliferation resistance

  1. Proliferation resistance of advanced sustainable nuclear fuel cycles

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, H.E.; Lineberry, M.J.; Aumeier, S.E.; McFarlane, H.F. [Argonne National Lab.-West (United States)

    2001-07-01

    Intrinsic and extrinsic proliferation barriers of a pyro-process-based nuclear fuel cycle are discussed. While technical characteristics of the process raise new challenges for safeguards, others naturally facilitate the implementation of more integrated schemes for unattended continuous monitoring. In particular, the concept of operations accountability and model-assisted methods are revisited. While traditional safeguards constructs, such as material control and accountability, place greater emphasis on input/output characterization of nuclear processes, a model- based discrete event accountability approach could explicitly verify not only facility use but also internal operational dynamics. Under the proposed remote integral safeguards approach, transparency can be achieved efficiently, without divulging competitive or national security sensitive information. (author)

  2. Proliferation resistance of advanced sustainable nuclear fuel cycles

    International Nuclear Information System (INIS)

    Garcia, H.E.; Lineberry, M.J.; Aumeier, S.E.; McFarlane, H.F.

    2001-01-01

    Intrinsic and extrinsic proliferation barriers of a pyro-process-based nuclear fuel cycle are discussed. While technical characteristics of the process raise new challenges for safeguards, others naturally facilitate the implementation of more integrated schemes for unattended continuous monitoring. In particular, the concept of operations accountability and model-assisted methods are revisited. While traditional safeguards constructs, such as material control and accountability, place greater emphasis on input/output characterization of nuclear processes, a model- based discrete event accountability approach could explicitly verify not only facility use but also internal operational dynamics. Under the proposed remote integral safeguards approach, transparency can be achieved efficiently, without divulging competitive or national security sensitive information. (author)

  3. Proliferation resistance modeling

    International Nuclear Information System (INIS)

    Bari, R.; Peterson, P.; Roglans, J.; Mladineo, S.; Nuclear Engineering Division; BNL; Univ. of California at Berkely; PNNL

    2004-01-01

    The National Nuclear Security Administration is developing methods for nonproliferation assessments. A working group on Nonproliferation Assessment Methodology (NPAM) assembled a toolbox of methods for various applications in the nonproliferation arena. One application of this methodology is to the evaluation of the proliferation resistance of Generation IV nuclear energy systems. This paper first summarizes the key results of the NPAM program and then provides results obtained thus far in the ongoing application, which is co-sponsored by the DOE Office of Nuclear Energy Science and Technology. In NPAM, a top-level measure of proliferation resistance for a fuel cycle system is developed from a hierarchy of metrics. The problem is decomposed into: metrics to be computed, barriers to proliferation, and a finite set of threats. The analyst models the process undertaken by the proliferant to overcome barriers to proliferation and evaluates the outcomes. In addition to proliferation resistance (PR) evaluation, the application also addresses physical protection (PP) evaluation against sabotage and theft. The Generation IV goal for future nuclear energy systems is to assure that they are very unattractive and the least desirable route for diversion or theft of weapons-usable materials, and provide increased physical protection against terrorism. An Expert Group, addressing this application, has identified six high-level measures for the PR goals (six measures have also been identified for the PP goals). Combined together, the complete set of measures provides information for program policy makers and system designers to compare specific system design features and integral system characteristics and to make choices among alternative options. The Group has developed a framework for a phased evaluation approach to analyzing PR and PP of system characteristics and to quantifying metrics and measures. This approach allows evaluations to become more detailed and representative

  4. Proliferation resistance fuel cycle technology

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. S.; Ko, W. I

    1999-02-01

    The issues of dual use in nuclear technology are analysed for nuclear fuel cycle with special focus on uranium enrichment and spent fuel reprocessing which are considered as the most sensitive components in terms of vulnerability to diversion. Technical alternatives to mitigrate the vulnerability, as has been analysed in depth during the NASAP and INFCE era in the late seventies, are reviewed to characterize the DUPIC fuel cycle alternative. On the other hand, the new realities in nuclear energy including the disposition of weapon materials as a legacy of cold war are recast in an angle of nuclear proliferation resistance and safeguards with a discussion on the concept of spent fuel standard concept and its compliance with the DUPIC fuel cycle technology. (author)

  5. Status of Methodology Development for the Evaluation of Proliferation Resistance

    International Nuclear Information System (INIS)

    Lee, Yong Deok; Ko, Won Il; Lee, Jung Won

    2010-01-01

    Concerning the increasing energy demand and green house effect, nuclear energy is now the most feasible option. Therefore, recently, oil countries even have a plan to build the nuclear power plant for energy production. If nuclear systems are to make a major and sustainable contribution to the worlds energy supply, future nuclear energy systems must meet specific requirements. One of the requirements is to satisfy the proliferation resistance condition in an entire nuclear system. Therefore, from the beginning of future nuclear energy system development, it is important to consider a proliferation resistance to prevent the diversion of nuclear materials. The misuse of a nuclear system must be considered as well. Moreover, in the import and export of nuclear system, the evaluation of the proliferation resistance on the nuclear system becomes a key factor The INPRO (International Project on Innovative Nuclear Reactors and Fuel Cycles) program initiated by the IAEA proposed proliferation resistance (PR) as a key component of a future innovative nuclear system (INS) with a sustainability, economics, safety of nuclear installation and waste management. The technical goal for Generation IV (Gen IV) nuclear energy systems (NESs) highlights a Proliferation Resistance and Physical Protection (PR and PP), sustainability, safety, reliability and economics as well. Based on INPRO and Gen IV study, the methodology development for the evaluation of proliferation resistance has been carried out in KAERI. Finally, the systematic procedure for methodology was setup and the indicators for the procedure were decided. The methodology involves the evaluation from total nuclear system to individual process. Therefore, in this study, the detailed procedure for the evaluation of proliferation resistance and the newly proposed additional indicators are described and several conditions are proposed to increase the proliferation resistance in the future nuclear system. The assessment of PR

  6. Framework of Comprehensive Proliferation Resistance Evaluation Methodology

    International Nuclear Information System (INIS)

    Kim, Min Su; Jo, Seong Youn; Kim, Min Soo; Kim, Jae San; Lee, Hyun Kyung

    2007-01-01

    Civilian nuclear programs can be used as a pretext to acquire technologies, materials, equipment for military weapon programs. Consequently, international society has a strong incentive to develop a nuclear system more proliferation resistant to assure that the civilian nuclear energy system is an unattractive and least desirable route for diversion of weapon usable material. The First step developing a more proliferation resistant nuclear energy system is to develop a systematic and standardized evaluation methodology to ensure that any future nuclear energy system satisfies the proliferation resistance goals. Many attempts to develop systematic evaluation methodology have been proposed and many systems for assessing proliferation resistance have been previously studied. However, a comprehensive proliferation resistance evaluation can not be achieved by simply applying one method since complicated proliferation resistance characteristics, including inherent features and extrinsic features, should be completely evaluated. Therefore, it is necessary to develop one incorporated evaluation methodology to make up for weak points of each evaluation method. The objective of this study is to provide a framework of comprehensive proliferation resistance evaluation methodology by incorporating two generally used evaluation methods, attribute and scenario analysis

  7. Comparative analysis of proliferation resistance assessment methodologies

    International Nuclear Information System (INIS)

    Takaki, Naoyuki; Kikuchi, Masahiro; Inoue, Naoko; Osabe, Takeshi

    2005-01-01

    Comparative analysis of the methodologies was performed based on the discussions in the international workshop on 'Assessment Methodology of Proliferation Resistance for Future Nuclear Energy Systems' held in Tokyo, on March 2005. Through the workshop and succeeding considerations, it is clarified that the proliferation resistance assessment methodologies are affected by the broader nuclear options being pursued and also by the political situations of the state. Even the definition of proliferation resistance, despite the commonality of fundamental issues, derives from perceived threat and implementation circumstances inherent to the larger programs. Deep recognitions of the 'difference' among communities would help us to make further essential and progressed discussion with harmonization. (author)

  8. Proliferation resistance of small modular reactors fuels

    Energy Technology Data Exchange (ETDEWEB)

    Polidoro, F.; Parozzi, F. [RSE - Ricerca sul Sistema Energetico,Via Rubattino 54, 20134, Milano (Italy); Fassnacht, F.; Kuett, M.; Englert, M. [IANUS, Darmstadt University of Technology, Alexanderstr. 35, D-64283 Darmstadt (Germany)

    2013-07-01

    In this paper the proliferation resistance of different types of Small Modular Reactors (SMRs) has been examined and classified with criteria available in the literature. In the first part of the study, the level of proliferation attractiveness of traditional low-enriched UO{sub 2} and MOX fuels to be used in SMRs based on pressurized water technology has been analyzed. On the basis of numerical simulations both cores show significant proliferation risks. Although the MOX core is less proliferation prone in comparison to the UO{sub 2} core, it still can be highly attractive for diversion or undeclared production of nuclear material. In the second part of the paper, calculations to assess the proliferation attractiveness of fuel in typical small sodium cooled fast reactor show that proliferation risks from spent fuel cannot be neglected. The core contains a highly attractive plutonium composition during the whole life cycle. Despite some aspects of the design like the sealed core that enables easy detection of unauthorized withdrawal of fissile material and enhances proliferation resistance, in case of open Non-Proliferation Treaty break-out, weapon-grade plutonium in sufficient quantities could be extracted from the reactor core.

  9. Proliferation resistance assessment of thermal recycle systems

    International Nuclear Information System (INIS)

    1979-02-01

    This paper examines the major proliferation aspects of thermal recycle systems and the extent to which technical or institutional measures could increase the difficulty or detectability of misuse of the system by would-be proliferators. It does this by examining the various activities necessary to acquire weapons-usable material using a series of assessment factors; resources required, time required, detectability. It is concluded that resistance to proliferation could be improved substantially by collecting reprocessing, conversion and fuel fabrication plants under multi national control and instituting new measures to protect fresh MOX fuel. Resistance to theft at sub-national level could be improved by co-location of sensitive facilities high levels of physical protection at plants and during transportation and possibly by adding a radiation barrier to MOX prior to shipment

  10. Proliferation Resistant Nuclear Reactor Fuel

    International Nuclear Information System (INIS)

    Gray, L.W.; Moody, K.J.; Bradley, K.S.; Lorenzana, H.E.

    2011-01-01

    Global appetite for fission power is projected to grow dramatically this century, and for good reason. Despite considerable research to identify new sources of energy, fission remains the most plentiful and practical alternative to fossil fuels. The environmental challenges of fossil fuel have made the fission power option increasingly attractive, particularly as we are forced to rely on reserves in ecologically fragile or politically unstable corners of the globe. Caught between a globally eroding fossil fuel reserve as well as the uncertainty and considerable costs in the development of fusion power, most of the world will most likely come to rely on fission power for at least the remainder of the 21st century. Despite inevitable growth, fission power faces enduring challenges in sustainability and security. One of fission power's greatest hurdles to universal acceptance is the risk of potential misuse for nefarious purposes of fissionable byproducts in spent fuel, such as plutonium. With this issue in mind, we have discussed intrinsic concepts in this report that are motivated by the premise that the utility, desirability, and applicability of nuclear materials can be reduced. In a general sense, the intrinsic solutions aim to reduce or eliminate the quantity of existing weapons usable material; avoid production of new weapons-usable material through enrichment, breeding, extraction; or employ engineering solutions to make the fuel cycle less useful or more difficult for producing weapons-usable material. By their nature, these schemes require modifications to existing fuel cycles. As such, the concomitants of these modifications require engagement from the nuclear reactor and fuel-design community to fully assess their effects. Unfortunately, active pursuit of any scheme that could further complicate the spread of domestic nuclear power will probably be understandably unpopular. Nevertheless, the nonproliferation and counterterrorism issues are paramount, and

  11. Analysis of nuclear proliferation resistance reprocessing and recycling technologies

    Energy Technology Data Exchange (ETDEWEB)

    Patricia Paviet-Hartmann; Gary Cerefice; Marcela Stacey; Steven Bakhtiar

    2011-05-01

    The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate – and should not be equated -with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. . Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R&D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

  12. Analysis of nuclear proliferation resistance reprocessing and recycling technologies

    International Nuclear Information System (INIS)

    Paviet-Hartmann, Patricia; Cerefice, Gary; Stacey, Marcela; Bakhtiar, Steven

    2011-01-01

    The PUREX process has been progressively and continuously improved during the past three decades, and these improvements account for successful commercialization of reprocessing in a few countries. The renewed interest in nuclear energy and the international growth of nuclear electricity generation do not equate - and should not be equated - with increasing proliferation risks. Indeed, the nuclear renaissance presents a unique opportunity to enhance the culture of non-proliferation. With the recent revival of interest in nuclear technology, technical methods for prevention of nuclear proliferation are being revisited. Robust strategies to develop new advanced separation technologies are emerging worldwide for sustainability and advancement of nuclear energy with enhanced proliferation resistance. On the other hand, at this moment, there are no proliferation resistance advanced technologies. Until now proliferation resistance as it applies to reprocessing has been focused on not separating a pure stream of weapons-usable plutonium. France, as an example, has proposed a variant of the PUREX process, the COEX TM process, which does not result on a pure plutonium product stream. A further step is to implement a process based on group extraction of actinides and fission products associated with a homogeneous recycling strategy (UNEX process in the US, GANEX process in France). Such scheme will most likely not be deployable on an industrial scale before 2030 or so because it requires intensive R and D and robust flowsheets. Finally, future generation recycling schemes will handle the used nuclear fuel in fast neutron reactors. This means that the plutonium throughput of the recycling process may increase. The need is obvious for advanced aqueous recycling technologies that are intrinsically more proliferation resistant than the commercial PUREX process. In this paper, we review the actual PUREX process along with the advanced recycling technologies that will enhance

  13. Proliferation resistance assessment of pyro processing

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, E. H.; Ko, W. I.; Kim, H. D. [KAERI, Daejeon (Korea, Republic of)

    2012-10-15

    In 2002, world experts gathered and defined the term proliferation resistance as 'the characteristic of a nuclear energy system that impedes the diversion or undeclared production of nuclear material, or misuse of technology, by State in order to acquire nuclear weapons or other nuclear explosive devices.' The same report also defines the following terms: Intrinsic barriers (technical features) of proliferation resistance are features that result from the technical design of nuclear energy systems, including those that facilitate the implementation of extrinsic measures. Extrinsic barriers (institutional measures) of proliferation resistance are features that result from the decisions and undertakings of states related to nuclear energy system. Intrinsic barriers are further divided into material barriers.the 'intrinsic, or inherent, qualities of materials that reduce the inherent desirability or attractiveness of the material as an explosive' and technical barriers. The 'intrinsic technical lements of the fuel cycle, its facilities, processes, and equipment that serve to make it difficult to gain access to materials and/or to use or misuse facilities to obtain weapons usable materials.' Material barriers include isotopic, chemical, radiological, mass and bulk, and detectability, whereas technical barriers include facility unattractiveness, accessibility, available fissile mass, detectability of and time required for diversion, and skills, expertise, and knowledge. Assessing the proliferation resistance of pyro processing is meaningful only when compared with other processes. This paper attempts to discuss the features of pyro processing by comparing it with direct disposal and aqueous separation processes from a proliferation resistance viewpoint.

  14. Proliferation resistance criteria for fissile material disposition

    International Nuclear Information System (INIS)

    Close, D.A.; Fearey, B.L.; Markin, J.T.; Rutherford, D.A.; Duggan, R.A.; Jaeger, C.D.; Mangan, D.L.; Moya, R.W.; Moore, L.R.; Strait, R.S.

    1995-04-01

    The 1994 National Academy of Sciences study open-quotes Management and Disposition of Excess Weapons Plutoniumclose quotes defined options for reducing the national and international proliferation risks of materials declared excess to the nuclear weapons program. This report proposes criteria for assessing the proliferation resistance of these options. The criteria are general, encompassing all stages of the disposition process from storage through intermediate processing to final disposition including the facilities, processing technologies and materials, the level of safeguards for these materials, and the national/subnational threat to the materials

  15. Technical features to enhance proliferation resistance of nuclear energy systems

    International Nuclear Information System (INIS)

    2010-01-01

    It is generally accepted that proliferation resistance is an essential issue for the continued development and sustainability of nuclear energy. Several comprehensive assessment activities on the proliferation resistance of the nuclear fuel cycle have previously been completed, notably the International Nuclear Fuel Cycle Evaluation (INFCE) carried out under the auspices of the IAEA, and the Non-proliferation Alternative Systems Assessment Program (NASAP) review carried out by the USA. There have been, however, relatively few comprehensive treatments of the issue following these efforts in the 1970s. However, interest in and concern about this issue have increased recently, particularly because of greater interest in innovative nuclear fuel cycles and systems. In 2000, the IAEA initiated the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) and the US Department of Energy initiated the Generation IV International Forum (GIF). These projects are aimed at the selection and development of concepts of innovative nuclear energy systems and fuel cycles. Proliferation resistance is one of the fundamental considerations for both projects. In this context, the IAEA in 2001 initiated a study entitled 'Technical Aspects of Increasing Proliferation Resistance of the Nuclear Fuel Cycle'. This task is not intended as an effort to assess the merits of a particular fuel cycle system for the future, but to describe a qualitative framework for an examination of the proliferation resistance provided by the intrinsic features of an innovative nuclear energy system and fuel cycle. This task also seeks to provide a high level survey of a variety of innovative nuclear energy systems and fuel cycles with respect to that framework. The concept of proliferation resistance is considered in terms of intrinsic features and extrinsic measures. The intrinsic features, sometimes referred to as the physical/technical aspects, are those features that result from the

  16. Proliferation resistance assessment of nuclear systems

    International Nuclear Information System (INIS)

    1978-09-01

    The paper focuses on examining the degree to which nuclear systems could be used to acquire nuclear weapons material. It establishes a framework for proliferation resistance assessment and illustrates its applicability through an analysis of reference systems for once-through cycles, breeder cycles and thermal recycle. On a more tentative basis, the approach is applied to various alternative technical and institutional measures. This paper was also submitted to Working Groups 5 and 8

  17. Proliferation resistance assessment of high temperature gas reactors

    Energy Technology Data Exchange (ETDEWEB)

    Chikamatsu N, M. A. [Instituto Tecnologico y de Estudios Superiores de Monterrey, Campus Santa Fe, Av. Carlos Lazo No. 100, Santa Fe, 01389 Mexico D. F. (Mexico); Puente E, F., E-mail: midori.chika@gmail.com [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2014-10-15

    The Generation IV International Forum has established different objectives for the new generation of reactors to accomplish. These objectives are focused on sustain ability, safety, economics and proliferation resistance. This paper is focused on how the proliferation resistance of the High Temperature Gas Reactors (HTGR) is assessed and the advantages that these reactors present currently. In this paper, the focus will be on explaining why such reactors, HTGR, can achieve the goals established by the GIF and can present a viable option in terms of proliferation resistance, which is an issue of great importance in the field of nuclear energy generation. The reason why the HTGR are being targeted in this writing is that these reactors are versatile, and present different options from modular reactors to reactors with the same size as the ones that are being operated today. Besides their versatility, the HTGR has designed features that might improve on the overall sustain ability of the nuclear reactors. This is because the type of safety features and materials that are used open up options for industrial processes to be carried out; cogeneration for instance. There is a small section that mentions how HTGR s are being developed in the international sector in order to present the current world view in this type of technology and the further developments that are being sought. For the proliferation resistance section, the focus is on both the intrinsic and the extrinsic features of the nuclear systems. The paper presents a comparison between the features of Light Water Reactors (LWR) and the HTGR in order to be able to properly compare the most used technology today and one that is gaining international interest. (Author)

  18. Proliferation resistance assessment of high temperature gas reactors

    International Nuclear Information System (INIS)

    Chikamatsu N, M. A.; Puente E, F.

    2014-10-01

    The Generation IV International Forum has established different objectives for the new generation of reactors to accomplish. These objectives are focused on sustain ability, safety, economics and proliferation resistance. This paper is focused on how the proliferation resistance of the High Temperature Gas Reactors (HTGR) is assessed and the advantages that these reactors present currently. In this paper, the focus will be on explaining why such reactors, HTGR, can achieve the goals established by the GIF and can present a viable option in terms of proliferation resistance, which is an issue of great importance in the field of nuclear energy generation. The reason why the HTGR are being targeted in this writing is that these reactors are versatile, and present different options from modular reactors to reactors with the same size as the ones that are being operated today. Besides their versatility, the HTGR has designed features that might improve on the overall sustain ability of the nuclear reactors. This is because the type of safety features and materials that are used open up options for industrial processes to be carried out; cogeneration for instance. There is a small section that mentions how HTGR s are being developed in the international sector in order to present the current world view in this type of technology and the further developments that are being sought. For the proliferation resistance section, the focus is on both the intrinsic and the extrinsic features of the nuclear systems. The paper presents a comparison between the features of Light Water Reactors (LWR) and the HTGR in order to be able to properly compare the most used technology today and one that is gaining international interest. (Author)

  19. Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

    Energy Technology Data Exchange (ETDEWEB)

    Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

    1979-01-19

    This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is more acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables.

  20. Proliferation resistance design of a plutonium cycle (Proliferation Resistance Engineering Program: PREP)

    International Nuclear Information System (INIS)

    Sorenson, R.J.; Roberts, F.P.; Clark, R.G.

    1979-01-01

    This document describes the proliferation resistance engineering concepts developed to counter the threat of proliferation of nuclear weapons in an International Fuel Service Center (IFSC). The basic elements of an International Fuel Service Center are described. Possible methods for resisting proliferation such as processing alternatives, close-coupling of facilities, process equipment layout, maintenance philosophy, process control, and process monitoring are discussed. Political and institutional issues in providing proliferation resistance for an International Fuel Service Center are analyzed. The conclusions drawn are (1) use-denial can provide time for international response in the event of a host nation takeover. Passive use-denial is more acceptable than active use-denial, and acceptability of active-denial concepts is highly dependent on sovereignty, energy dependence and economic considerations; (2) multinational presence can enhance proliferation resistance; and (3) use-denial must be nonprejudicial with balanced interests for governments and/or private corporations being served. Comparisons between an IFSC as a national facility, an IFSC with minimum multinational effect, and an IFSC with maximum multinational effect show incremental design costs to be less than 2% of total cost of the baseline non-PRE concept facility. The total equipment acquisition cost increment is estimated to be less than 2% of total baseline facility costs. Personnel costs are estimated to increase by less than 10% due to maximum international presence. 46 figures, 9 tables

  1. Proliferation resistance assessment of nuclear systems

    International Nuclear Information System (INIS)

    1978-09-01

    The first part of the present paper describes the basic assessment procedure that is adopted in the analysis of the three generic nuclear systems. Once-through, fast breeder, and thermal recycle systems are then treated in Sections II, III, and IV, respectively. In each of these sections, a reference system is examined, possible technical and institutional improvements are considered, and alternative system types are indicated. Section V then discusses the relative proliferation resistance of the three generic systems. Although this paper emphasizes the analysis and comparison of individual fuel cycle alternatives, Section V indicates briefly how these analyses then have to be considered in a broader context where systems coexist

  2. Proliferation resistance of the lithium reduction process

    International Nuclear Information System (INIS)

    Ko, W. I.; Ha, J. H.; Lee, S. Y.; Song, D. Y.; Kim, H. D.; Park, S. W.

    2002-01-01

    This paper addresses the characteristics of proliferation resistance of the lithium reduction process and international domestic safeguarding methods. In addition to dealing with qualitative features of the proliferation resistance, this study is emphasizing on the quantitative analysis of radiation barrier, which could be a significant accessibility barrier if the field is high enough to force a theft to shield the object during a theft. From the radiation barrier analysis, it is indicated that whole-body radiation dose is about 20 rem/hr at one meter of smelt and ingot metal of 40 kgHM, which could be considered to be a significant reduction in risk of theft. For safeguarding of this process, we propose a NDA concept for nuclear material accounting which is to measure the amount of curium in the reduction metal and associated process samples using a neutron coincidence counter and then to convert the curium mass into special nuclear material with predetermined curium ratios. For this, a well-type neutron coincidence counter with substantial shielding to protect the system from high gamma radiation is conceptually designed

  3. Criteria for proliferation resistance of nuclear fuel cycle options

    International Nuclear Information System (INIS)

    Kiriyama, Eriko; Pickett, Susan; Suzuki, Tatsujiro

    2000-01-01

    In order to understand the concept of nuclear proliferation resistance, this paper examines the technical definitions of proliferation resistance. Although nuclear proliferation resistance is often included as one of the major goals of advanced reactor research and development, the criteria for nuclear proliferation resistance of nuclear fuel cycles is not defined clearly. The implied meaning of proliferation resistance was compared in proposals regarding the nuclear fuel cycle. Discrepancies amongst the proposals regarding the technical definition of proliferation resistance is found. While all these proposals indicate proliferation resistance, few clearly spell out exactly what criteria they are measuring themselves against. However we found there are also common feature in many proposals. They are; (1) Reduction of Pu, (2) Less separated Weapon Usable Materials, (3) Fewer steps, (4) Barrier for Weapon Usable Materials. Recognizing that there are numerous political and infrastructure measures that may also be taken to guard against proliferation risks, we have focused here on the definition of proliferation resistance in terms of technical characteristics. Another important conclusion is that in many proposals proliferation resistance is only one of the important criteria such as energy security, economical efficiency, and safety. (author)

  4. Model for evaluating nuclear strategies with proliferation resistance

    International Nuclear Information System (INIS)

    Shay, M.R.; Hardie, R.W.; Omberg, R.P.

    1979-03-01

    A model was developed at HEDL to specifically analyze proliferation resistant strategies. The model was not designed to predict the future, but rather to provide a method for estimating the consequences of decisions affecting proliferation resistance in a rational and plausible manner. The characteristics of the model are described

  5. Evaluation of proliferation resistance using the INPRO methodology

    International Nuclear Information System (INIS)

    Yang, Myung Seung; Park, Joo Hwan; Ko, Won Il; Song, Kee Chan; Choi, Kun Mo; Kim, Jin Kyoung

    2007-01-01

    The IAEA launched the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) and developed the INPRO Methodology to provide guidelines and to assess the characteristics of a future innovative nuclear energy system in areas such as safety, economics, waste management, and proliferation resistance. The proliferation resistance area of the INPRO Methodology is reviewed here, and modifications for further improvements are proposed. The evaluation metrics including the evaluation parameters, evaluation scales and acceptance limits are developed for a practical application of the methodology to assess the proliferation resistance. The proliferation resistant characteristics of the DUPIC fuel cycle are assessed by applying the modified INPRO Methodology based on the developed evaluation metrics and acceptance criteria. The evaluation procedure and the metrics can be utilized as a reference for an evaluation of the proliferation resistance of a future innovative nuclear energy system

  6. Methodologies for evaluating the proliferation resistance of nuclear fuel cycles

    International Nuclear Information System (INIS)

    Shiotani, Hiroki; Hori, Kei-ichiro; Takeda, Hiroshi

    2001-01-01

    The Japan Nuclear Cycle Development Institute (JNC) believes that the development of future nuclear fuel cycle technology should be conducted with careful consideration given to non-proliferation. JNC is studying methodologies for evaluating proliferation resistance of nuclear fuel cycle technologies. However, it is difficult to establish the methodology for evaluating proliferation resistance since the results greatly depend on the assumption for the evaluation and the surrounding conditions. This study grouped factors of proliferation resistance into categories through reviewing past studies and studied the relationships between the factors. Then, this study tried to find vulnerable nuclear material (plutonium) in some FBR fuel cycles from the proliferation perspective, and calculated the time it takes to convert the materials from various nuclear fuel cycles into pure plutonium metal under some assumptions. The result showed that it would take a long time to convert the nuclear materials from the FBR fuel cycles without plutonium separation. While it is a preliminary attempt to evaluate a technical factor of proliferation resistance as the basis of the institutional proliferation resistance, the JNC hopes that it will contribute to future discussions in this area. (author)

  7. Model for nuclear proliferation resistance analysis using decision making tools

    International Nuclear Information System (INIS)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2003-06-01

    The nuclear proliferation risks of nuclear fuel cycles is being considered as one of the most important factors in assessing advanced and innovative nuclear systems in GEN IV and INPRO program. They have been trying to find out an appropriate and reasonable method to evaluate quantitatively several nuclear energy system alternatives. Any reasonable methodology for integrated analysis of the proliferation resistance, however, has not yet been come out at this time. In this study, several decision making methods, which have been used in the situation of multiple objectives, are described in order to see if those can be appropriately used for proliferation resistance evaluation. Especially, the AHP model for quantitatively evaluating proliferation resistance is dealt with in more detail. The theoretical principle of the method and some examples for the proliferation resistance problem are described. For more efficient applications, a simple computer program for the AHP model is developed, and the usage of the program is introduced here in detail. We hope that the program developed in this study could be useful for quantitative analysis of the proliferation resistance involving multiple conflict criteria

  8. Model for nuclear proliferation resistance analysis using decision making tools

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2003-06-01

    The nuclear proliferation risks of nuclear fuel cycles is being considered as one of the most important factors in assessing advanced and innovative nuclear systems in GEN IV and INPRO program. They have been trying to find out an appropriate and reasonable method to evaluate quantitatively several nuclear energy system alternatives. Any reasonable methodology for integrated analysis of the proliferation resistance, however, has not yet been come out at this time. In this study, several decision making methods, which have been used in the situation of multiple objectives, are described in order to see if those can be appropriately used for proliferation resistance evaluation. Especially, the AHP model for quantitatively evaluating proliferation resistance is dealt with in more detail. The theoretical principle of the method and some examples for the proliferation resistance problem are described. For more efficient applications, a simple computer program for the AHP model is developed, and the usage of the program is introduced here in detail. We hope that the program developed in this study could be useful for quantitative analysis of the proliferation resistance involving multiple conflict criteria.

  9. ASSESSING THE PROLIFERATION RESISTANCE OF INNOVATIVE NUCLEAR FUEL CYCLES

    International Nuclear Information System (INIS)

    BARI, R.; ROGLANS, J.; DENNING, R.; MLADINEO, S.

    2003-01-01

    The National Nuclear Security Administration is developing methods for nonproliferation assessments to support the development and implementation of U.S. nonproliferation policy. This paper summarizes the key results of that effort. Proliferation resistance is the degree of difficulty that a nuclear material, facility, process, or activity poses to the acquisition of one or more nuclear weapons. A top-level measure of proliferation resistance for a fuel cycle system is developed here from a hierarchy of metrics. At the lowest level, intrinsic and extrinsic barriers to proliferation are defined. These barriers are recommended as a means to characterize the proliferation characteristics of a fuel cycle. Because of the complexity of nonproliferation assessments, the problem is decomposed into: metrics to be computed, barriers to proliferation, and a finite set of threats. The spectrum of potential threats of nuclear proliferation is complex and ranges from small terrorist cells to industrialized countries with advanced nuclear fuel cycles. Two general categories of methods have historically been used for nonproliferation assessments: attribute analysis and scenario analysis. In the former, attributes of the systems being evaluated (often fuel cycle systems) are identified that affect their proliferation potential. For a particular system under consideration, the attributes are weighted subjectively. In scenario analysis, hypothesized scenarios of pathways to proliferation are examined. The analyst models the process undertaken by the proliferant to overcome barriers to proliferation and estimates the likelihood of success in achieving a proliferation objective. An attribute analysis approach should be used at the conceptual design level in the selection of fuel cycles that will receive significant investment for development. In the development of a detailed facility design, a scenario approach should be undertaken to reduce the potential for design vulnerabilities

  10. User requirements and criteria for proliferation resistance in INPRO

    International Nuclear Information System (INIS)

    Choi, K.; Shea, T.E.; Hurt, R.D.; Nishimura, R.

    2004-01-01

    In designing future nuclear energy systems, it is important to consider the potential that such systems could be misused for the purpose of producing nuclear weapons. INPRO set out to provide guidance on incorporating proliferation resistance into innovative nuclear energy systems (INS). Generally two types of proliferation resistance measures are distinguished: intrinsic and extrinsic. Intrinsic features consist of technical design features that reduce the attractiveness of nuclear material for nuclear weapon program, or prevent the diversion of nuclear material or production of undeclared nuclear material for nuclear weapons. Extrinsic measures include commitments, obligations and policies of states such as the Treaty on the Non-Proliferation of Nuclear Weapons (NPT) and IAEA safeguards agreements. INPRO has produced five basic principles and five user requirements for INS. It emphasizes that INS must continue to be an unattractive means to acquire fissile material for a nuclear weapon program. It also addresses as user requirements: 1) a balanced and optimised combination of intrinsic features and extrinsic measures, 2) the development and implementation of intrinsic features, 3) an early consideration of proliferation resistance in the development of INS and 4) the utilization of intrinsic features to increase the efficiency of extrinsic measures. INPRO has also developed criteria, consisting of indicators and acceptance limits, which would be used by a state to assess how an INS satisfies those user requirements. For the first user requirement, the most important but complex one, INPRO provides a 3-layer hierarchy of indicators to assess how unattractive a specific INS would be as part of a nuclear weapon program. Attributes of nuclear material and facilities are used as indicators to assess intrinsic features. Extrinsic measures imposed on the system are also assessed. Indicators to assess defence in depth for proliferation resistance include the number and

  11. Revised INPRO Methodology in the Area of Proliferation Resistance

    International Nuclear Information System (INIS)

    Park, J.H.; Lee, Y.D.; Yang, M.S.; Kim, J.K.; Haas, E.; Depisch, F.

    2008-01-01

    The official INPRO User Manual in the area of proliferation resistance is being processed for the evaluation of innovative nuclear energy systems. Proliferation resistance is one of the goals to be satisfied for future nuclear energy systems in INPRO. The features of currently updated and released INPRO methodology were introduced on basic principles, user requirements and indicators. The criteria for an acceptance limit were specified. The DUPIC fuel cycle was evaluated based on the updated INPRO methodology for the applicability of the INPRO User Manual. However, the INPRO methodology has some difficulty in quantifying the multiplicity and robustness as well as the total cost to improve proliferation resistance. Moreover, the integration method for the evaluation results still needs to be improved.

  12. Complexities in gauging time-dependency of proliferation resistance

    International Nuclear Information System (INIS)

    Avens, L.R.; Eller, P.G.; Stanbro, W.D.

    2004-01-01

    To a considerable extent, policy decisions on nuclear fuel cycle issues depend upon how decision makers recognize and weigh 'long-term' and 'short-term' nuclear proliferation risk factors. Priorities and structures of advanced fuel cycle and safeguards research and development programs are affected similarly. Unfortunately, there is a diversity of understanding of the precise meanings of these proliferation risk terms, leading to lack of precision in their usage. In addition, proliferation risk evaluation fundamentally involves value judgments on the relative importance of time-dependent risks. Poor communication and diverse conclusions often result. This paper explores some complexities in gauging 'long-term' and 'short-term' proliferation risk in the context of advanced nuclear fuel cycles. A convenient vehicle for this purpose is a commonly used notional plot of some proliferation resistance attribute of spent fuel or separated plutonium versus years from reactor discharge, often overlain with similar notional curves denoting multiple fuel irradiation and recycle. A common basis for misuse of such plots is failure to clearly define the range of proliferation threats being evaluated, as illustrated by several common examples of such omissions. Partial arguments of this type can be misleading and provide a disservice to policy makers who must have a clear picture of the tradeoffs being made. This paper concludes with a call for much greater care to avoid overly simplistic interpretations of notional proliferation-related concepts and greater precision in general in use of proliferation-related terminology.

  13. INCREASED PROLIFERATION RESISTANCE FOR 21ST CENTURY NUCLEAR POWER

    International Nuclear Information System (INIS)

    Demuth, Scott F.; Thomas, Ken E.; Wallace, Richard K.

    2007-01-01

    World energy demand and greenhouse gases are expected to significantly increase in the near future. Key developing countries have identified nuclear power as a major contributor to their future energy sources. Consequently, the US and others are currently exploring the concept of a Global Nuclear Energy Partnership (GNEP) to address the concerns of nuclear proliferation. This effort is also being encouraged by the International Atomic Energy Agency (IAEA). While the IAEA currently provides the framework for monitoring of state sponsored nuclear proliferation by way of international treaties, a complimentary action is to promote more proliferation resistant fuel cycles and advanced safeguards technology. As such, it is the responsibility of current technology owners to increase their nuclear fuel cycle proliferation resistance. For those countries that have an active and well-developed fuel cycle, it will require future enhancements. For those countries with extensive nuclear energy experience, yet less active programs, it requires re-engagement for technology development and deployment. The following paper discusses potential fuel cycle and technology changes that affect proliferation resistance; and consequently, may form the basis of future technology development efforts.

  14. Methodological considerations in evaluating a proliferation resistance of innovative nuclear energy systems

    International Nuclear Information System (INIS)

    Kikuchi, Masahiro; Takaki, Naoyuki; Murajiri, Masahiro; Nakagome, Yoshihiro; Tokiwai, Moriyasu

    2004-01-01

    Over 25 years ago, INFCE studied the evaluation methodology of proliferation resistance. Recently, INPRO and GEN-IV coordinated by the IAEA and the USDOE respectively seek an appropriate innovative fuel cycle system for next generation that is furnished safer, sustainable, economical and reliable features. The evaluation methodology of the proliferation resistance is also assigned as an essential part of both studies. The IAEA established and has been strictly implementing the verification measures with accurate material accountancy system from the early of the 1970s in order to detect diversion of plutonium that is individually separated from irradiated nuclear material and recycled as MOX fuel. This paper firstly identifies the impedibility of intrinsic features of innovative fuel cycles and the safeguardability of selected nonproliferation measures as two individual essential parameters for evaluation of a proliferation resistance capability. As a next step, this paper also shows methodological considerations in evaluating the proliferation resistance levels as a multiple model of several clusters that are identified the ability of each parameter. (author)

  15. Proliferation resistance criteria for fissile material disposition issues

    International Nuclear Information System (INIS)

    Rutherford, D.A.; Fearey, B.L.; Markin, J.T.; Close, D.A.; Tolk, K.M.; Mangan, D.L.; Moore, L.

    1995-01-01

    The 1994 National Acdaemy of Sciences study ''Management and Disposition of Excess Weapons Plutonium'' defined options for reducing the national and international proliferation risks of materials declared excess to the nuclear weapons program. This paper proposes criteria for assessing the proliferation resistance of these options as well defining the ''Standards'' from the report. The criteria are general, encompassing all stages of the disposition process from storage through intermediate processing to final disposition including the facilities, processing technologies and materials, the level of safeguards for these materials, and the national/subnational threat to the materials

  16. Enhancing VVER annular proliferation resistance fuel with minor actinides

    International Nuclear Information System (INIS)

    Chang, G. S.

    2007-01-01

    Key aspects of the Global Nuclear Energy Partnership (GNEP) are to significantly advance the science and technology of nuclear energy systems and the Advanced Fuel Cycle (AFC) program. It consists of both innovative nuclear reactors and innovative research in separation and transmutation. To accomplish these goals, international cooperation is very important and public acceptance is crucial. The merits of nuclear energy are high-density energy, with low environmental impacts (i.e. almost zero greenhouse gas emission). Planned efforts involve near term and intermediate-term improvements in fuel utilization and recycling in current light water reactors (LWRs) as well as the longer-term development of new nuclear energy systems that offer much improved fuel utilization and proliferation resistance, along with continued advances in operational safety. The challenges are solving the energy needs of the world, protection against nuclear proliferation, the problem of nuclear waste, and the global environmental problem. To reduce spent fuel for storage and enhance the proliferation resistance for the intermediate-term, there are two major approaches (a) increase the discharged spent fuel burnup in the advanced LWR (Gen-III Plus), which not only can reduce the spent fuel for storage, but also increase the 2 38Pu and 2 40Pu isotopes ratio to enhance the proliferation resistance, and (b) use of transuranic nuclides ( 2 37Np and 2 41Am) in the high burnup fuel, which can drastically increase the proliferation resistance isotope ratio of 2 38Pu /Pu. For future advanced nuclear systems, the minor actinides (MA) are viewed more as a resource to be recycled, or transmuted to less hazardous and possibly more useful forms, rather than simply as a waste stream to be disposed of in expensive repository facilities. As a result, MAs play a much larger part in the design of advanced systems and fuel cycles, not only as additional sources of useful energy, but also as direct contributors

  17. MEHODOLOGY FOR PROLIFERATION RESISTANCE FOR ADVANCE NUCLEAR ENERGY SYSTEMS

    International Nuclear Information System (INIS)

    YUE, M.; CHANG, L.Y.; BARI, R.

    2006-01-01

    The Technology Goals for Generation IV nuclear energy systems highlight Proliferation Resistance and Physical Protection (PRandPP) as one of the four goal areas for Generation 1V nuclear technology. Accordingly, an evaluation methodology is being developed by a PRandPP Experts Group. This paper presents a possible approach, which is based on Markov modeling, to the evaluation methodology for Generation IV nuclear energy systems being developed for PRandPP. Using the Markov model, a variety of proliferation scenarios can be constructed and the proliferation resistance measures can be quantified, particularly the probability of detection. To model the system with increased fidelity, the Markov model is further developed to incorporate multiple safeguards approaches in this paper. The approach to the determination of the associated parameters is presented. Evaluations of diversion scenarios for an example sodium fast reactor (ESFR) energy system are used to illustrate the methodology. The Markov model is particularly useful because it can provide the probability density function of the time it takes for the effort to be detected at a specific stage of the proliferation effort

  18. Energy-efficiency and proliferation-resistance assessment factors

    International Nuclear Information System (INIS)

    1979-02-01

    Assessment factors suggested with regard to energy efficiency are: preservation of natural non-renewable resources: the degree of security of supply which can be achieved; the availability of necessary raw materials and technology; economic feasibility; and acceptability of a fuel cycle from environmental and safety views. In the area of proliferation resistance, it is suggested that the basic element is the political commitment by a Government not to use imported nuclear materials and equipment to manufacture nuclear explosives. 100% proliferation resistance is considered unattainable in practice. The role of international safeguards in detering possible diversion through the risk of early detection is described, and it is argued that efficient safeguards will force a Government willing to go nuclear to withdraw from its safeguards agreements. The second assessment factor, accordingly, is to consider different fuel cycles with regard to the efficient and rapid building up of a nuclear weapons capacity once the country has withdrawn from its safeguards commitments

  19. Development of proliferation resistance assessment methodology based on international standard

    International Nuclear Information System (INIS)

    Ko, W. I.; Chang, H. L.; Lee, Y. D.; Lee, J. W.; Park, J. H.; Kim, Y. I.; Ryu, J. S.; Ko, H. S.; Lee, K. W.

    2012-04-01

    Nonproliferation is one of the main requirements to be satisfied by the advanced future nuclear energy systems that have been developed in the Generation IV and INPRO studies. The methodologies to evaluate proliferation resistance has been developed since 1980s, however, the systematic evaluation approach has begun from around 2000. Domestically a study to develop national method to evaluate proliferation resistance (PR) of advanced future nuclear energy systems has started in 2007 as one of the long-term nuclear R and D subjects in order to promote export and international credibility and transparency of national nuclear energy systems and nuclear fuel cycle technology development program. In the first phase (2007-2010) development and improvement of intrinsic evaluation parameters for the evaluation of proliferation resistance, quantification of evaluation parameters, development of evaluation models, and development of permissible ranges of evaluation parameters have been carried out. In the second phase (2010-2012) generic principle of to evaluate PR was established, and techincal guidelines, nuclear material diversion pathway analysis method, and a method to integrate evaluation parameters have been developed. which were applied to 5 alternative nuclear fuel cycles to estimate their appicability and objectivity. In addition, measures to enhance PR of advanced future nuclear energy systems and technical guidelines of PR assessment using intrinsic PR evaluation parameters were developed. Lastly, requlatory requirements to secure nonproliferation requirements of nuclear energy systems from the early design stage, operation and to decommissioning which will support the export of newly developed advanced future nuclear energy system

  20. Enhancing BWR proliferation resistance fuel with minor actinides

    Science.gov (United States)

    Chang, Gray S.

    2009-03-01

    To reduce spent fuel for storage and enhance the proliferation resistance for the intermediate-term, there are two major approaches (a) increase the discharged spent fuel burnup in the advanced light water reactor- LWR (Gen-III Plus), which not only can reduce the spent fuel for storage, but also increase the 238Pu isotopes ratio to enhance the proliferation resistance, and (b) use of transuranic nuclides ( 237Np and 241Am) in the high burnup fuel, which can drastically increase the proliferation resistance isotope ratio of 238Pu/Pu. For future advanced nuclear systems, minor actinides (MA) are viewed more as a resource to be recycled, and transmuted to less hazardous and possibly more useful forms, rather than simply disposed of as a waste stream in an expensive repository facility. As a result, MAs play a much larger part in the design of advanced systems and fuel cycles, not only as additional sources of useful energy, but also as direct contributors to the reactivity control of the systems into which they are incorporated. In the study, a typical boiling water reactor (BWR) fuel unit lattice cell model with UO 2 fuel pins will be used to investigate the effectiveness of minor actinide reduction approach (MARA) for enhancing proliferation resistance and improving the fuel cycle performance in the intermediate-term goal for future nuclear energy systems. To account for the water coolant density variation from the bottom (0.76 g/cm 3) to the top (0.35 g/cm 3) of the core, the axial coolant channel and fuel pin were divided to 24 nodes. The MA transmutation characteristics at different elevations were compared and their impact on neutronics criticality discussed. The concept of MARA, which involves the use of transuranic nuclides ( 237Np and/or 241Am), significantly increases the 238Pu/Pu ratio for proliferation resistance, as well as serves as a burnable absorber to hold-down the initial excess reactivity. It is believed that MARA can play an important role in

  1. Modeling and evaluating proliferation resistance of nuclear energy systems for strategy switching proliferation

    International Nuclear Information System (INIS)

    Yue, M.; Cheng, L.-Y.; Bari, R.A.

    2013-01-01

    Highlights: ► Sensitivity analysis is carried out for the model and physical input parameters. ► Interphase drag has minor effect on the dryout heat flux (DHF) in 1D configuration. ► Model calibration on pressure drop experiments fails to improve prediction of DHF. ► Calibrated classical model provides the best agreement with DHF data from 1D tests. ► Further validation of drag models requires data from 2D and 3D experiments on DHF. - Abstract: This paper reports a Markov model based approach to systematically evaluating the proliferation resistance (PR) of nuclear energy systems (NESs). The focus of the study is on the development of the Markov models for a class of complex PR scenarios, i.e., mixed covert/overt strategy switching proliferation, for NESs with two modes of material flow, batch and continuous. In particular, a set of diversion and/or breakout scenarios and covert/overt misuse scenarios are studied in detail for an Example Sodium Fast Reactor (ESFR) system. Both probabilistic and deterministic PR measures are calculated using a software tool that implements the proposed approach and can be used to quantitatively compare proliferation resistant characteristics of different scenarios for a given NES, according to the computed PR measures

  2. Assessment of proliferation resistance of thermal recycle systems

    International Nuclear Information System (INIS)

    1979-02-01

    An assessment is made of the proliferation resistance of thermal recycle systems. The safeguards aspects are not addressed. Three routes to the acquisition of materials for nuclear weapons are addressed namely; a deliberate political decision by a government involving the use of dedicated facilities, a deliberate political decision by government involving abuse of nuclear fuel cycle facilities and theft by a subnational group. The most sensitive parts of the reference fuel cycle and the alternative technical measures are examined to judge their relative sensitivity. This is done by examining the difference forms in which plutonium can exist in the fuel cycle. The role which different institutional arrangements can play is also evaluated. From this comparative assessment it is concluded that, taking into account the qualitative nature of the assessment, the different stages of development of the various fuel cycles, the various realizations possible in respect of the deployment of facilities within individual countries and the evolutionary nature of the technical and institutional improvements foreseeable no fuel cycle can be made completely free from abuse. Furthermore it appears that following progressive introduction of features that will improve proliferation resistance there will not be significant differences between the various fuel cycles when compared at the point in time when they are introduced into widespread use. Provided such features are developed and implemented there is no reason on proliferation grounds to prefer one cycle to another

  3. Sustaining non-proliferation in the 1980s

    International Nuclear Information System (INIS)

    Nye, J.S.

    1984-01-01

    The subject is discussed as follows: introduction; the non-proliferation regime - 1950s to 1970s (IAEA safeguards; Non-proliferation Treaty; oil crisis; proposed sale of facilities for producing weapons-usable materials; USA position); the Carter Administration approach; INFCE (International Nuclear Fuel Cycle Evaluation); incentives (USA); export legislation (USA); domestic breeder policy (USA); maintaining the regime in the 1980s (safeguards; Pu and highly enriched uranium management; international spent fuel storage; fuel assurances); the problem of priority; rate vs. degree of proliferation; relations among regimes (international regimes); conclusion. (U.K.)

  4. Proliferation resistance considerations for remote small modular reactors

    Energy Technology Data Exchange (ETDEWEB)

    Whitlock, J., E-mail: whitlockj@aecl.ca [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada); Sprinkle, J., E-mail: j.sprinkle@iaea.org [International Atomic Energy Agency, Vienna (Austria)

    2013-07-01

    Remotely located Small Modular Reactors at the low end of energy production (on the order of 10 MWe, referenced here as Very Small Modular Reactors or VSMRs) present unique proliferation resistance advantages and challenges. Addressing these challenges in the most efficient manner may not only be desirable, but necessary, for development of this technology. Incorporation of safeguards considerations early in the design process (Safeguards by Design) along with safety, security, economics and other key drivers, is of importance. Operational Transparency may become an essential aspect of the safeguards approach for such systems. (author)

  5. PROLIFERATION RESISTANCE AND PHYSICAL PROTECTION WORKING GROUP: METHODOLOGY AND APPLICATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Bari R. A.; Whitlock, J.; Therios, I.U.; Peterson, P.F.

    2012-11-14

    We summarize the technical progress and accomplishments on the evaluation methodology for proliferation resistance and physical protection (PR and PP) of Generation IV nuclear energy systems. We intend the results of the evaluations performed with the methodology for three types of users: system designers, program policy makers, and external stakeholders. The PR and PP Working Group developed the methodology through a series of demonstration and case studies. Over the past few years various national and international groups have applied the methodology to nuclear energy system designs as well as to developing approaches to advanced safeguards.

  6. Proliferation resistance and physical protection working group: methodology and applications

    International Nuclear Information System (INIS)

    Bari, Robert A.; Whitlock, Jeremy J.; Therios, Ike U.; Peterson, P.F.

    2012-01-01

    We summarize the technical progress and accomplishments on the evaluation methodology for proliferation resistance and physical protection (PR and PP) of Generation IV nuclear energy systems. We intend the results of the evaluations performed with the methodology for three types of users: system designers, program policy makers, and external stakeholders. The PR and PP Working Group developed the methodology through a series of demonstration and case studies. Over the past few years various national and international groups have applied the methodology to nuclear energy system designs as well as to developing approaches to advanced safeguards.

  7. A strategic framework for proliferation resistance: a systematic approach for the identification and evaluation of technology opportunities to enhance the proliferation resistance of civilian nuclear energy systems

    International Nuclear Information System (INIS)

    Hassberger, J.A.; Isaac, T.; Schock, R.N.

    2001-01-01

    The United State Department of Energy Nuclear Energy Research Advisory Committee recently completed a study ''Technological Opportunities To Increase The Proliferation Resistance Of Global Civilian Nuclear Power Systems (TOPS)''. That effort included the development of a set of both intrinsic and extrinsic barriers to proliferation that technologies can directly impact. In this paper we will review these barriers as and framework for assisting in the evaluation of the relative proliferation resistance of various nuclear fuel cycles, technologies and alternatives. (author)

  8. Proliferation Resistance and Safeguards by Design: The Safeguardability Assessment Tool Provided by the INPRO Collaborative Project ''INPRO'' (Proliferation Resistance and Safeguardability Assessment)

    International Nuclear Information System (INIS)

    Haas, E.; Chang, H.-L.; Phillips, J.R.; Listner, C.

    2015-01-01

    Since the INPRO Collaborative Project on Proliferation Resistance and Safeguardability Assessment Tools (PROSA) was launched in 2011, Member State experts have worked with the INPRO Section and the IAEA Department of Safeguards to develop a revised methodology for self-assessment of sustainability in the area of proliferation resistance of a nuclear energy system (NES). With the common understanding that there is ''no proliferation resistance without safeguards'' the revised approach emphasizes the evaluation of a new 'User Requirement' for ''safeguardability'', that combines metrics of effective and efficient implementation of IAEA Safeguards including ''Safeguards-by-Design'' principles. The assessment with safeguardability as the key issue has been devised as a linear process evaluating the NES against a ''Basic Principle'' in the area of proliferation resistance, answering fundamental questions related to safeguards: 1) Do a State's legal commitments, policies and practices provide credible assurance of the exclusively peaceful use of the NES, including a legal basis for verification activities by the IAEA? 2) Does design and operation of the NES facilitate the effective and efficient implementation of IAEA safeguards? To answer those questions, a questionnaire approach has been developed that clearly identifies gaps and weaknesses. Gaps include prospects for improvements and needs for research and development. In this context, the PROSA approach assesses the safeguardability of a NES using a layered ''Evaluation Questionnaire'' that defines Evaluation Parameters (EP), EP-related questions, Illustrative Tests and Screening Questions to present and structure the evidence of findings. An integral part of the assessment process is Safeguards-by-Design, the identification of potential diversion, misuse and concealment strategies (coarse diversion path

  9. Teleconference highlights-NE-NA proliferation resistance review

    International Nuclear Information System (INIS)

    Miller, Michael C.

    2009-01-01

    Herczeg gave a readout from the kickoff meeting with Paul Lisowski - namely develop a common definition of proliferation resistance (for use by S-1, other upper management, public affairs, etc.), and to evaluate possible framework where a metric could be assigned for fuel cycle comparisons (integral, easy to communicate). Sprinkle raised concern about 'trivializing' notion of proliferation resistance (PR), with idea of making sure we don't lose the concept that strong safeguards and security are required within a nonproliferation framework that support U.S. policy goals. Integrated Safeguards by Design notion was brought up in this context. Round table discussion of the term PR, its misuse (even unintentional), fact that Chu is using term and apparently in context of proliferation proof. It was noted that there has been much work already done in this area and we should not reinvent the wheel. One of the first tasks needs to be gathering up old reports (TOPS, Como, PRPP, etc) and distributing to group (action item for all). It was also noted that there are multiple definitions of PR, including the recent NPIA, supporting the need for this type of activity. Miller described the current work package under AFCI, with $50k of funding from the campaign management account. Herczeg asked about additional funds should it become clear that a larger effort is required (tension between current program and getting something out relatively soon). Goldner to look into potential additional funds. Miller notes that within current work package, easy to engage LANL participants and that Per Peterson can participate under UCB funding (a new center is being established with UC fee awards from LANL and LLNL - the Berkeley Nuclear Research Center). Consensus that Per would be a good external member of the group. Sprinkle notes that held like to coordinate the NE and NA work packages. Miller and Sprinkle to work offline. Wallace talked about the possibility of being more quantitative in

  10. Partitioning and transmutation - Technical feasibility, proliferation resistance and safeguardability

    International Nuclear Information System (INIS)

    Schenkel, R.; Glatz, J.-P.; Magill, J.; Mayer, K.

    2001-01-01

    combined with a transmutation cycle (second stratum). Here, the first separation of radiotoxic elements from the PUREX high-level liquid waste could be achieved by advanced aqueous partitioning. In the following transmutation cycle, pyroreprocessing should be used, because of a number of advantages; those are a higher compactness of equipment and the possibility to form an integrated system between irradiation and reprocessing facility (reduced transport of nuclear materials and process costs in general) higher radiation stability of the salt in the pyrochemical process compared to the organic solvent in the hydrochemical process offers an important advantage when dealing with highly active spent MA fuel compared with aqueous methods, dry reprocessing results in less pure and thus more proliferation resistant fractions of Pu, Np and Am. In particular the latter aspect is important in view of the attractiveness of products for proliferation. In the paper the different partitioning processes, aqueous and dry, will be briefly described and analyzed for their strengths and weaknesses in view of safeguards and proliferation. Furthermore, the advantages and drawbacks of homogeneous and heterogeneous cycles will be discussed in view of proliferation resistance and safeguardability. (author)

  11. Final report on LDRD project ''proliferation-resistant fuel cycles''

    International Nuclear Information System (INIS)

    Brown, N W; Hassberger, J A.

    1999-01-01

    This report provides a summary of LDRD work completed during 1997 and 1998 to develop the ideas and concepts that lead to the Secure, Transportable, Autonomous Reactor (STAR) program proposals to the DOE Nuclear Energy Research Initiative (NERI). The STAR program consists of a team of three national laboratories (LLNL, ANL, and LANL), three universities, (UC Berkeley, TAMU, and MIT) and the Westinghouse Research Center. Based on the LLNL work and their own efforts on related work this team prepared and integrated a package of twelve proposals that will carry the LDRD work outlined here into the next phase of development. We are proposing to develop a new nuclear system that meets stringent requirements for a high degree of safety and proliferation resistance, and also deals directly with the related nuclear waste and spent fuel management issues

  12. A Comparison of Proliferation Resistance Measures of Misuse Scenarios Using a Markov Approach

    International Nuclear Information System (INIS)

    Yue, M.; Cheng, L.-Y.; Bari, R.

    2008-01-01

    Misuse of declared nuclear facilities is one of the important proliferation threats. The robustness of a facility against these threats is characterized by a number of proliferation resistance (PR) measures. This paper evaluates and compares PR measures for several misuse scenarios using a Markov model approach to implement the pathway analysis methodology being developed by the PR and PP (Proliferation Resistance and Physical Protection) Expert Group. Different misue strategies can be adopted by a proliferator and each strategy is expected to have different impacts on the proliferator's success. Selected as the probabilistic measure to represent proliferation resistance, the probabilities of the proliferator's success of misusing a hypothetical ESFR (Example Sodium Fast Reactor) facility system are calculated using the Markov model based on the pathways constructed for individual misuse scenarios. Insights from a comparison of strategies that are likely to be adopted by the proliferator are discussed in this paper.

  13. Sustainably Sourced, Thermally Resistant, Radiation Hard Biopolymer

    Science.gov (United States)

    Pugel, Diane

    2011-01-01

    This material represents a breakthrough in the production, manufacturing, and application of thermal protection system (TPS) materials and radiation shielding, as this represents the first effort to develop a non-metallic, non-ceramic, biomaterial-based, sustainable TPS with the capability to also act as radiation shielding. Until now, the standing philosophy for radiation shielding involved carrying the shielding at liftoff or utilizing onboard water sources. This shielding material could be grown onboard and applied as needed prior to different radiation landscapes (commonly seen during missions involving gravitational assists). The material is a bioplastic material. Bioplastics are any combination of a biopolymer and a plasticizer. In this case, the biopolymer is a starch-based material and a commonly accessible plasticizer. Starch molecules are composed of two major polymers: amylase and amylopectin. The biopolymer phenolic compounds are common to the ablative thermal protection system family of materials. With similar constituents come similar chemical ablation processes, with the potential to have comparable, if not better, ablation characteristics. It can also be used as a flame-resistant barrier for commercial applications in buildings, homes, cars, and heater firewall material. The biopolymer is observed to undergo chemical transformations (oxidative and structural degradation) at radiation doses that are 1,000 times the maximum dose of an unmanned mission (10-25 Mrad), indicating that it would be a viable candidate for robust radiation shielding. As a comparison, the total integrated radiation dose for a three-year manned mission to Mars is 0.1 krad, far below the radiation limit at which starch molecules degrade. For electron radiation, the biopolymer starches show minimal deterioration when exposed to energies greater than 180 keV. This flame-resistant, thermal-insulating material is non-hazardous and may be sustainably sourced. It poses no hazardous

  14. Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2000-07-01

    This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity.

  15. Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

    International Nuclear Information System (INIS)

    Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

    2000-07-01

    This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity

  16. Development of Proliferation Resistance Assessment Methodology Based on International Standards

    International Nuclear Information System (INIS)

    Lee, Yong Deok; Lee, Jung Won; Lee, Kwang Seok

    2009-03-01

    Proliferation resistance is one of the requirement to be met in GEN IV and INPRO for next generation nuclear energy system. Internationally, the evaluation methodology on PR had been already initiated from 1980, but the systematic development was started at 2000s. In Korea, for the export of nuclear energy system and the increase of international credibility and transparence of domestic nuclear system and fuel cycle development, the independent development of PR evaluation methodology was started in 2007 as a nuclear long term R and D project and the development is being performed for the model of PR evaluation methodology. In 1st year, comparative study of GEN-IV/INPRO, PR indicator development, quantification of indicator and evaluation model development, analysis of technology system and international technology development trend had been performed. In 2nd year, feasibility study of indicator, allowable limit of indicator, review of technical requirement of indicator were done. The results of PR evaluation must be applied in the beginning of conceptual design of nuclear system. Through the technology development of PR evaluation methodology, the methodology will be applied in the regulatory requirement for authorization and permission to be developed

  17. Establishment of Assessment Methodology Improvement of IAEA INPRO Proliferation Resistance

    International Nuclear Information System (INIS)

    Park, J. H.; Yang, M. S.; Song, K. C.; Ko, W. I.; Kim, H. D.; Kim, Y. I.; Rhee, B. W.; Kim, H. T.

    2008-03-01

    For the development of assessment methodology of acquisition and diversion pathway of nuclear material, the PR assessment methodology which has been developed by GEN-IV PR and PP group was reviewed regarding the acquisition and diversion pathway of nuclear material and we proposed the research areas to develop the model of acquisition and diversion pathway of nuclear material including misuse of fuel cycle facilities and one of the IAEA INPRO CRPs which is aiming to develop its model. From the present study, its preliminary model for acquisition and diversion pathway of nuclear material was obtained. For preliminary evaluation of DUPIC system using methodology of acquisition/diversion pathway of nm and review of pyro-processing system characteristics, the research direction and work procedure was established to develop the assessment methodology of User Requirement 4 of INPRO PR by; 1) selection of the possible pathway to acquire and divert the nuclear material of DUPIC system, 2) the analysis of selected pathway, 3) the development of the assessment methodology of robustness and multiplicity of an INS. And, the PR characteristics and process/material flow analysis of the Pyro-processing system were preliminarily studied. For establishment of R and D direction for an INS and supporting international cooperation research, the collaborative research project titled as 'Acquisition and Diversion pathway analysis of Proliferation Resistance' as one of activities of IAEA INPRO was proposed, since Korean Government decided to actively support the IAEA INPRO. In order to review and clarify the Terms of Reference (TOR) of a Korean Proposed Collaborative Project (ROK1), two INPRO Consultancy Meetings were held. Its results were presented at two INPRO Steering Committees and the finalized TOR of Korean Proposal submit the 12-th INPRO Steering Committee Meeting which was held Dec. 3-5 2007. Four participants including USA, Canada, China and European Community (EC) have decided

  18. Establishment of Assessment Methodology Improvement of IAEA INPRO Proliferation Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Park, J. H.; Yang, M. S.; Song, K. C.; Ko, W. I.; Kim, H. D.; Kim, Y. I.; Rhee, B. W.; Kim, H. T.

    2008-03-15

    For the development of assessment methodology of acquisition and diversion pathway of nuclear material, the PR assessment methodology which has been developed by GEN-IV PR and PP group was reviewed regarding the acquisition and diversion pathway of nuclear material and we proposed the research areas to develop the model of acquisition and diversion pathway of nuclear material including misuse of fuel cycle facilities and one of the IAEA INPRO CRPs which is aiming to develop its model. From the present study, its preliminary model for acquisition and diversion pathway of nuclear material was obtained. For preliminary evaluation of DUPIC system using methodology of acquisition/diversion pathway of nm and review of pyro-processing system characteristics, the research direction and work procedure was established to develop the assessment methodology of User Requirement 4 of INPRO PR by; 1) selection of the possible pathway to acquire and divert the nuclear material of DUPIC system, 2) the analysis of selected pathway, 3) the development of the assessment methodology of robustness and multiplicity of an INS. And, the PR characteristics and process/material flow analysis of the Pyro-processing system were preliminarily studied. For establishment of R and D direction for an INS and supporting international cooperation research, the collaborative research project titled as 'Acquisition and Diversion pathway analysis of Proliferation Resistance' as one of activities of IAEA INPRO was proposed, since Korean Government decided to actively support the IAEA INPRO. In order to review and clarify the Terms of Reference (TOR) of a Korean Proposed Collaborative Project (ROK1), two INPRO Consultancy Meetings were held. Its results were presented at two INPRO Steering Committees and the finalized TOR of Korean Proposal submit the 12-th INPRO Steering Committee Meeting which was held Dec. 3-5 2007. Four participants including USA, Canada, China and European Community (EC

  19. An Introduction to The Interdisciplinary Concept of Risk-Informed Proliferation Resistance

    International Nuclear Information System (INIS)

    Gouveia, Fernando

    2010-01-01

    The nonproliferation community is rich in diverse attempts aimed at predicting and preventing attempts at nuclear proliferation. Such efforts, however, are rarely incorporated into a holistic approach well-suited to solving both existing and emerging proliferation dilemmas. This division is particularly apparent with respect to the partition that separates the socio-political and technical approaches to solving such problems, approaches which are very often developed and utilized in isolation. Complicating matters further, are the diverse positions taken by various entities as they relate to the secure implementation of nuclear energy world-wide. Such positions range from the obdurate belief in the supposed inherent proliferation resistance of traditional spent fuel, to those regarding all nuclear energy systems as inherently proliferation prone, given their core reliance on the sensitive technologies of enrichment and reprocessing. Accordingly, moderates have argued for a risk-informed approach to combat nuclear proliferation, combining institutional factors, such as IAEA safeguards, with innovative reactor and fuel designs to bring about an acceptable notion of proliferation resistance. To this end, methodologies have been developed, which seek to assess and score attained proliferation resistance. Most notably, these include, the Proliferation Resistance and Physical Protection (PR and PP) methodology prepared by the GEN-IV International Forum and the IAEA's International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). Such approaches have greatly advanced the concept of proliferation resistance; however, they remain limited by their exclusive concentration on the technological determinants of proliferation and non-consideration of other, equally important, socio-political determinants. This limitation is significant as numerous incidents have illustrated the ability of atypical states to find alternate paths to proliferation, for example

  20. A Comparison of the Safety Analysis Process and the Generation IV Proliferation Resistance/Physical Protection Assessment Methodology

    International Nuclear Information System (INIS)

    T. A. Bjornard; M. D. Zentner

    2006-01-01

    The Generation IV International Forum (GIF) is a vehicle for the cooperative international development of future nuclear energy systems. The Generation IV program has established primary objectives in the areas of sustainability, economics, safety and reliability, and Proliferation Resistance and Physical Protection (PR and PP). In order to help meet the latter objective a program was launched in December 2002 to develop a rigorous means to assess nuclear energy systems with respect to PR and PP. The study of Physical Protection of a facility is a relatively well established methodology, but an approach to evaluate the Proliferation Resistance of a nuclear fuel cycle is not. This paper will examine the Proliferation Resistance (PR) evaluation methodology being developed by the PR group, which is largely a new approach and compare it to generally accepted nuclear facility safety evaluation methodologies. Safety evaluation methods have been the subjects of decades of development and use. Further, safety design and analysis is fairly broadly understood, as well as being the subject of federally mandated procedures and requirements. It is therefore extremely instructive to compare and contrast the proposed new PR evaluation methodology process with that used in safety analysis. By so doing, instructive and useful conclusions can be derived from the comparison that will help to strengthen the PR methodological approach as it is developed further. From the comparison made in this paper it is evident that there are very strong parallels between the two processes. Most importantly, it is clear that the proliferation resistance aspects of nuclear energy systems are best considered beginning at the very outset of the design process. Only in this way can the designer identify and cost effectively incorporate intrinsic features that might be difficult to implement at some later stage. Also, just like safety, the process to implement proliferation resistance should be a dynamic

  1. Neutronic simulation calculations to assess the proliferation resistance of nuclear technologies

    International Nuclear Information System (INIS)

    Englert, Matthias

    2009-01-01

    This thesis investigates the proliferation resistance of nuclear technologies on the basis of three case studies. After a brief description of the concept of proliferation resistance the utilized computer codes and methods are presented. The first case study investigates the potential of monolithic fuel for the conversion of one-fuel-element high-flux research reactors from highly enriched to low enriched uranium using the example of the german research reactor FRM-II. The second case study assesses the proliferation potential of future tokamak based fusion reactors by using neutronic simulations of a possible plutonium production. The third example investigates the proliferation potential of spallation neutron sources to produce nuclear weapon relevant material and the proliferation resistance of such facilities. (orig.)

  2. A collaboration on development of requirements and guidelines for proliferation resistance of future nuclear system in the IAEA INPRO

    International Nuclear Information System (INIS)

    Oh, Keun Bae; Lee, Kwang Seok; Kim, Hyun Jun; Jeong, Ik; Yang, Myung Seung; Ko, Won Il

    2003-10-01

    This study surveyed and analyzed the existing activities and international status concerning proliferation resistance of nuclear energy systems, reviewed the features of proliferation resistance, and derived the requirements of future innovative nuclear energy systems. In IAEA INPRO, guidance for the evaluation of innovative nuclear reactors and fuel cycles on proliferation resistance was finalized through collaboration of member countries including Korea in reviewing technological status and developing the methodology for evaluation of proliferation resistance. This report, first, describes the progress of INPRO and the participation status of Korea in the project, and briefly summarizes the report of phase IA of INPRO. Next, features of proliferation resistance of nuclear systems, collaboration in the GIF and the INPRO for development of requirements and guidelines for proliferation resistance, and the final result of guidance for the evaluation of proliferation resistance were described. Finally, this study proposed measures for participation of further progress of the INPRO

  3. Sustainability transition dynamics: Towards overcoming policy resistance

    NARCIS (Netherlands)

    Gooyert, V. de; Rouwette, E.A.J.A.; Kranenburg, H.L. van; Freeman, R.E.; Breen, H.J. van

    2016-01-01

    Sustainability transitions receive major scholarly attention, often explicitly with the intention to develop policy recommendations aimed towards progressing such transitions. Despite these efforts, many implemented transition policies have not been able to meet expectations. This tendency of

  4. A Study on the Improvement of the INPRO Proliferation Resistance Assessment Methodology

    International Nuclear Information System (INIS)

    Ko, Won Il; Chang, Hong Lae

    2010-07-01

    Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed. However, User Requirement (UR) 4 regarding multiplicity and robustness of barriers against proliferation ('innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures') remains to be developed. Because the development of a methodology for evaluating User Requirement 4 requires an acquisition/diversion pathway analysis, a systematic approach was developed for the identification and analysis of pathways for the acquisition of weapons-useable nuclear material. This approach was applied to the DUPIC fuel cycle which identified several proliferation target materials and plausible acquisition/diversion pathways. Based on these results, proliferation strategies that a proliferant State could adopt for undeclared removal of nuclear material from the DUPIC fuel cycle have been developed based on the objectives of the proliferation of the State, the quality and quantity of the target material, the time required to acquire the material for the proliferation, and the technical and financial capabilities of the potential proliferant State. The diversion pathway for fresh DUPIC fuel was analyzed using the INPRO User Requirements 1, 2 and 3, and based on these results an assessment procedure and metrics for evaluating the multiplicity and robustness of proliferation barriers has been developed. In conclusion, the multiplicity and robustness of proliferation barriers is not a function of the number of barriers, or of their individual characteristics but is an integrated function of the whole. The robustness of proliferation barriers is measured by determining whether the safeguards goals can be met. The harmonization of INPRO PR methodology with the GIF PR and PP methodology was also considered. It was suggested that, as also confirmed by IAEA

  5. A study on the proliferation resistance evaluation methodology for nuclear energy system

    International Nuclear Information System (INIS)

    Kim, Min Su

    2007-02-01

    The framework of proliferation resistance evaluation methodology, based on attribute analysis and scenario analysis, for nuclear energy system is suggested in order to allow for the comprehensive assessment of proliferation resistance by addressing the intrinsic and extrinsic features of nuclear energy system. Proliferation resistance is viewed within the context of the success tree model of proliferator's diversion attempt and expressed by the value of top event probability of the success tree model. This study focused on the method that the value of top event is estimated. The methodology uses two different methods to quantify the likelihood of basic events constituting the top event. The likelihood of basic event success affected by intrinsic feature of nuclear energy system was assessed by using multi-attribute utility theory and likelihood of basic event related to the diversion detection measures was assessed by direct expert elicitation. The value of top event was calculated based on the intersection of probabilities of basic event success. Feasibility of the methodology was explored by applying it to selected reference nuclear energy systems. System-Integrated Modular Advanced Reactor (SMART) system and Light Water Reactor (LWR) were chosen as reference systems and the value proliferation resistance of SMART and LWR were evaluated. Characteristics of inherent features and hypothesized safeguards measures of both systems were identified and used as input data to evaluate proliferation resistance. The results and conclusions are applicable only within the context of subjectivity of this methodology

  6. Tanoak resistance: can it be used to sustain populations?

    Science.gov (United States)

    Katherine J. Hayden; Alex Lundquist; Douglas J. Schmidt; Richard A. Sniezko; Susan J. Frankel; Matteo. Garbelotto

    2010-01-01

    Tanoak (Lithocarpus densiflorus) trees are among Phytophthora ramorum’s most susceptible hosts. Extensive mortality in this species has led researchers to question whether selective breeding for resistance can be used to sustain populations; the answer depends on the extent and heritability of pathogen resistance within the...

  7. Acquisition/Diversion Pathway Analysis of the DUPIC Fuel Cycle for the Assessment of Proliferation Resistance

    International Nuclear Information System (INIS)

    Chang, Hong Lae; Ko, Won Il

    2008-01-01

    Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) of the IAEA, a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed in order to provide guidance in using the INPRO methodology. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation (innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures). To develop the assessment procedure and metrics for User Requirement 4 (UR4), the coarse acquisition/ diversion pathway analysis of the DUPIC Fuel Cycle has been performed. The most plausible pathways for the acquisition of weapons-usable nuclear material were identified and analyzed using a systematic approach herein, and future work to complete the assessment approach for the UR4 of the INPRO methodology regarding the multiplicity and robustness of barriers against proliferation are also proposed

  8. Acquisition/Diversion Pathway Analysis for the Assessment of Proliferation Resistance

    International Nuclear Information System (INIS)

    Chang, Hong Lae; Ko, Won Il

    2009-01-01

    The INPRO methodology in the area of proliferation resistance (PR) has one basic principle and five user requirements with relevant criteria, indicators, evaluation parameters, etc. The two Korean case studies on proliferation resistance of the DUPIC fuel cycle during 2004 and 2005 and various consultancy meetings have contributed to the establishment of the assessment metrics and procedures for three user requirements regarding States' commitment, attractiveness of nuclear material and technology, and difficulty and detectability of diversion. However, the assessment indicators and procedure for user requirement 4 regarding multiplicity and robustness of barriers against proliferation still need to be developed. In this paper, a systematic approach to identify and analyze the acquisition/diversion pathways in a nuclear energy system is described, including follow-up R and D plans to assess the multiplicity and robustness of barriers against proliferation

  9. Underpinning sustainable vector control through informed insecticide resistance management.

    Directory of Open Access Journals (Sweden)

    Edward K Thomsen

    Full Text Available There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia's programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions.A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids, DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s.Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management plan.

  10. Proliferation Resistance: Acquisition/Diversion Pathway Analysis for the DUPIC Fuel Cycle

    International Nuclear Information System (INIS)

    Ko, Won Il; Chang, Hong Lae; Song, Dae Yong; Lee, Ho Hee; Kwon, Eun Ha; Jeong, Chang Joon; Kim, Ho Dong

    2009-07-01

    Within the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO), a methodology for evaluating proliferation resistance (INPRO PR methodology) has been developed. However, it remains to develop the methodology to evaluate User Requirements (UR) 4 regarding multiplicity and robustness of barriers against proliferation - innovative nuclear energy systems should incorporate multiple proliferation resistance features and measures. Since this requires an acquisition/diversion pathway analysis, this report describes a systematic approach developed for the identification and analysis of pathways for the acquisition of weapons-usable nuclear material using the DUPIC fuel cycle system. At the first step, the objectives of the proliferation were identified, including the quality and quantity of the material, the time required to acquire the material for the proliferation, thr capability of the potential proliferant country, etc. At the second step, the possible strategies, which the potential proliferant country could adopt, were identified: undeclared removal of nuclear material from the fuel cycle facilities; and further treatment of the diverted nuclear materials needed to acquire weapons-usable materials. At the final step, a systematic approach to select the plausible pathways for the acquisition/diversion of nuclear material during the whole fuel cycle has been developed. The coarse material diversion pathways for the DUPIC fuel cycle and the approach developed was reviewed and discussed at the experts meeting at the IAEA for its appropriateness and comprehensiveness

  11. Application of the Decision Tree Modeling Approach to Evaluation of Proliferation Resistance

    International Nuclear Information System (INIS)

    Coles, Garill A.; Zentner, Michael D.

    2007-01-01

    An experts group was created in 2002 by The Generation IV International Forum for the purpose of developing an internationally accepted methodology for assessing the proliferation resistance of a nuclear energy system (NES) and its individual elements. After three years of work, and some limited demonstration studies, a pilot study was initiated to exercise the methodologies being developed by assessing the proliferation resistance of a specific portion of a hypothetical NES called the Example Sodium Fast Reactor (ESFR). This paper summarizes the assessment approach, and describes the next steps to be taken in the development of the methodology.

  12. INPRO Collaborative Project: Proliferation Resistance: Acquisition/Diversion Pathway Analysis (PRADA)

    International Nuclear Information System (INIS)

    2012-05-01

    This publication contributes to strengthening the assessment area of proliferation resistance of the INPRO methodology. The basic principle for this area requires that multiple intrinsic features and extrinsic measures of proliferation resistance be implemented throughout the full life cycle of an innovative nuclear energy system to help ensure that the system will continue to be an unattractive means of acquiring fissile material for a nuclear weapons programme. A typical intrinsic feature is the dilution of plutonium with fission products as found in irradiated material, and a typical extrinsic measure is the placing of nuclear material under international safeguards.

  13. Proliferation resistance characteristics of advanced nuclear energy systems: a safeguard ability point of view

    International Nuclear Information System (INIS)

    Sevini, F.; Cojazzi, G.G.M.; Renda, G.

    2008-01-01

    Among the international community there is a renewed interest in nuclear power systems as a major source for energy production in the near to mid future. This is mainly due to concerns connected with future availability of conventional energy resources, and with the environmental impact of fossil fuels. International initiatives have been set up like the Generation 4. International Forum (GIF), the International Project on Innovative Nuclear Reactors and Fuel Cycles (IAEA-INPRO), and, partially, the US driven Global Nuclear Energy Partnership (GNEP), aimed at defining and evaluating the characteristics, in which future innovative nuclear energy systems (INS) will have to excel. Among the identified characteristics, Proliferation Resistance plays an important role for being able to widely deploy nuclear technology worldwide in a secure way. Studies having the objective to assess Proliferation Resistance of nuclear fuel cycles have been carried out since the nineteen seventies, e.g., the International Nuclear Fuel Cycle Evaluation (INFCE) and the Non-proliferation Alternative Systems Assessment Program (NASAP) initiatives, and all agree in stating that absolute intrinsic proliferation resistance, although desirable, is not achievable in the foreseeable future. The above finding is still valid; as a consequence, every INS will have to comply with agreements related to the Non Proliferation Treaty (NPT) and will require safeguards measures, implemented through extrinsic measures. This consideration led to a renewed interest in the Safeguard ability concept which can be seen as a bridge between intrinsic features and extrinsic features and measures.

  14. Improving the proliferation resistance of research and test reactors

    International Nuclear Information System (INIS)

    Lewis, R.A.

    1978-01-01

    Elimination, or substantial reduction, of the trade in unirradiated highly-enriched fuel elements for research and test reactors would significantly reduce the proliferation risk associated with the current potential for diversion of these materials. To this end, it is the long-term goal of U.S. policy to fuel all new and existing research and test reactors with uranium of less-than-20% enrichment (but substantially greater than natural) excepting, perhaps, only a small number of high-power, high-performance, reactors. The U.S. development program for enrichment reduction in research and test reactor designs currently using 90-93% enriched uranium is based on the practical criterion that enrichment reduction should not cause significant flux performance (flux per unit power) or burnup performance degradation relative to the unmodified reactor design. To first order, this implies the requirement that the 235 U loading in the reduced-enrichment fuel elements be the same as the 235 U loading in the 90-93% enriched fuel elements. This can be accomplished by substitution of higher uranium density fuel technology for currently-used fuel technology in the fuel meat volume of the current fuel element design and/or by increasing the usable fuel meat volume. For research and test reactors of power greater than 5-10 megawatts, fuel technology does not currently exist that would permit enrichment reductions to below 20% utilizing this criterion. A program is now beginning in the U.S. to develop the necessary fuel technology. Currently-proven fuel technology is capable, however, of accommodating enrichment reductions to the 30-45% range (from 90-93%) for many reactors in the 5-50MW range. Accordingly the U.S. is proposing to convert existing reactors (and new designs) in the 5-50MW range from the use of highly-enriched fuel to the use of 30-45% enriched fuel, and reactors of less that about 5MW to less-than-20% enrichment, wherever this can be done without significant

  15. Stanniocalcin 2 promotes cell proliferation and cisplatin resistance in cervical cancer

    International Nuclear Information System (INIS)

    Wang, Yuxia; Gao, Ying; Cheng, Hairong; Yang, Guichun; Tan, Wenhua

    2015-01-01

    Cervical cancer is one of the most common carcinomas in the female reproductive system. Treatment of cervical cancer involves surgical removal and chemotherapy. Resistance to platinum-based chemotherapy drugs including cisplatin has increasingly become an important problem in the treatment of cervical cancer patients. We found in this study that stanniocalcin 2 (STC2) expression was upregulated in both cervical cancer tissues and cell lines. The levels of STC2 expression in cervical cancer cell lines were positively correlated with the rate of cell proliferation. Furthermore, in cisplatin resistant cervical cancer cells, the levels of STC2 expression were significantly elevated. Modulation of STC2 expression by siRNA or overexpression in cisplatin resistant cells resulted in altered cell survival, apoptosis, and cisplatin resistance. Finally, we found that there was significant difference in the activity of the MAPK signaling pathway between cisplatin sensitive and resistant cervical cancer cells, and that STC2 could regulate the activity of the MAPK signaling pathway. - Highlights: • STC2 was upregulated in cervical cancer and promoted cervical cancer cell proliferation. • Cisplatin resistant cells had elevated STC2 levels and enhanced proliferation. • STC2 regulated cisplatin chemosensitivity in cervical cancer cells. • STC2 regulated the activity of the MAPK signaling pathway.

  16. Nuclear proliferation and civilian nuclear power. Report of the Nonproliferation Alternative Systems Assessment Program. Volume II. Proliferation resistance

    International Nuclear Information System (INIS)

    1980-06-01

    The purpose of this volume is limited to an assessment of the relative effects that particular choices of nuclear-power systems, for whatever reasons, may have on the possible spread of nuclear-weapons capabilities. This volume addresses the concern that non-nuclear-weapons states may be able to initiate efforts to acquire or to improve nuclear-weapons capabilities through civilian nuclear-power programs; it also addresses the concern that subnational groups may obtain and abuse the nuclear materials or facilities of such programs, whether in nuclear-weapons states (NWS's) or nonnuclear-weapons states (NNW's). Accordingly, this volume emphasizes one important factor in such decisions, the resistance of nuclear-power systems to the proliferation of nuclear-weapons capabilities

  17. Intrinsically secure fast reactors for long-lived waste free and proliferation resistant nuclear power

    International Nuclear Information System (INIS)

    Slessarev, Igor

    2008-01-01

    This paper provides description of a nuclear reactor concept aimed towards a radical safety enhancement, an increased proliferation resistance, as well as a realisation of a 'long-lived waste free' NP development. It emphasizes the achievement of considerable reduction ('by design') of residual actinides in the waste streams and of the most hazardous long-lived fission products. It allows to implement only small volume of repositories for the radioactive waste (mostly fission products) and to postpone the technically arduous problems of a large scale disposal of the long-lived wastes until the next millennium, i.e. up to the exhaustion of the fertile natural resources and/or the emergence of more effective technologies of nuclide separation/transmutation. A thorough incineration/transmutation of the wastes (residual actinides in the mixture with lanthanides as well as of the most hazardous fission products) under reactor neutron flux is proposed for their mass reduction. A gradual growth of NP park is necessary for increasing the NP park capacity for waste irradiation. This 'constraint' is not really limiting because it coincides with the permanently growing demands in energy production. The potential of long-lived waste reduction depends on the total fertile fuel resources and on NP growth rate. It was shown that the accumulated actinide long-lived radioactive masses will be reduced significantly: by factor in the range of 10 4 -10 8 in magnitude (compared with LWR once-through cycle) and by 10 2 -10 6 (compared with the ordinary fast reactor park). Thus, the total long-lived waste toxicity pollution source might be comparable with the 'burnt away' toxicity of the natural fertile feed stream. This is quite realistic taking into account the large fertile fuel (U/Th) world-wide resources which provide the NP growth for a sustained time. Along side with the radical intrinsic safety improvement, a further enhancement of core physics ('neutronics') is one of the

  18. Peroxisome Proliferator-Activated Receptors and Hepatitis C Virus-Induced Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Francesco Negro

    2009-01-01

    Full Text Available Insulin resistance and type 2 diabetes are associated with hepatitis C virus infection. A wealth of clinical and experimental data suggests that the virus is directly interfering with the insulin signalling in hepatocytes. In the case of at least one viral genotype (the type 3a, insulin resistance seems to be directly mediated by the downregulation of the peroxisome proliferator-activated receptor γ. Whether and how this interaction may be manipulated pharmacologically, in order to improve the responsiveness to antivirals of insulin resistant chronic hepatitis C, patients remain to be fully explored.

  19. Proliferation Resistance and Material Type considerations within the Collaborative Project for a European Sodium Fast Reactor

    International Nuclear Information System (INIS)

    Renda, Guido; Alim, Fatih; Cojazzi, Giacomo GM.

    2015-01-01

    The collaborative project for a European Sodium Fast Reactor (CP‑ESFR) is an international project where 25 European partners developed Research & Development solutions and concepts for a European sodium fast reactor. The project was funded by the 7. European Union Framework Programme and covered topics such as the reactor architectures and components, the fuel, the fuel element and the fuel cycle, and the safety concepts. Within sub‑project 3, dedicated to safety, a task addressed proliferation resistance considerations. The Generation IV International Forum (GIF) Proliferation Resistance and Physical Protection (PR and PP) Evaluation Methodology has been selected as the general framework for this work, complemented by punctual aspects of the IAEA‑INPRO Proliferation Resistance methodology and other literature studies - in particular for material type characterization. The activity has been carried out taking the GIF PR and PP Evaluation Methodology and its Addendum as the general guideline for identifying potential nuclear material diversion targets. The targets proliferation attractiveness has been analyzed in terms of the suitability of the targets’ nuclear material as the basis for its use in nuclear explosives. To this aim the PR and PP Fissile Material Type measure was supplemented by other literature studies, whose related metrics have been applied to the nuclear material items present in the considered core alternatives. This paper will firstly summarize the main ESFR design aspects relevant for PR following the structure of the GIF PR and PP White Paper template. An analysis on proliferation targets is then discussed, with emphasis on their characterization from a nuclear material point of view. Finally, a high‑level ESFR PR analysis according to the four main proliferation strategies identified by the GIF PR and PP Evaluation Methodology (concealed diversion, concealed misuse, breakout, clandestine production in clandestine facilities) is

  20. Advanced core concepts with enhanced proliferation resistance by transmutation of minor actinides

    International Nuclear Information System (INIS)

    Saito, Masaki

    2005-01-01

    ''Protected Plutonium Production (P 3 )'' has been proposed to establish high burn-up cores and to produce protected with high proliferation resistance due to high decay heat and large number of spontaneous fission neutron of 238 Pu by the transmutation of Minor Actinides (MAs) which is presently treated as high-level waste. The burn-up calculations have shown that the advanced fuel with UO 2 (11-13% enrichment of 235 U) by doping 237 Np to produce 238 Pu in the commercialized large LWRs burn up to 100 GWd/t with 238 Pu to Pu ratio of about 20% which means the fuel is highly protected from proliferation. It was also predicted that medium or small size LWR cores with 15-17% enrichment, liquid metal cooled cores, and gas cooled cores added by 1-2% Np could achieve 100 GWd/t burning with bearing high proliferation resistance. The 237 Np mass balance calculations have revealed that more than 20 nuclear P 3 plants of 300 MWe could be supplied with enough 237 Np from the Japanese commercial plants in equilibrium fuel cycles. From the present studies, it is confirmed that MAs are treated as burnable and fertile materials not only to extend the core life but also to improve plutonium proliferation resistance of the future nuclear energy systems instead of their geological disposal or just their burning through fission. (author)

  1. Nuclear proliferation-resistance and safeguards for future nuclear fuel cycle

    International Nuclear Information System (INIS)

    Kuno, Y.; Inoue, N.; Senzaki, M.

    2009-01-01

    Corresponding to the world nuclear security concerns, future nuclear fuel cycle (NFC) should have high proliferation-resistance (PR) and physical protection (PP), while promotion of the peaceful use of the nuclear energy must not be inhibited. In order to accomplish nuclear non-proliferation from NFC, a few models of the well-PR systems should be developed so that international community can recognize them as worldwide norms. To find a good balance of 'safeguard-ability (so-called extrinsic measure or institutional barrier)' and 'impede-ability (intrinsic feature or technical barrier)' will come to be essential for NFC designers to optimize civilian nuclear technology with nuclear non-proliferation, although the advanced safeguards with high detectability can still play a dominant role for PR in the states complying with full institutional controls. Accomplishment of such goal in a good economic efficiency is a future key challenge

  2. Nuclear proliferation-resistance and safeguards for future nuclear fuel cycle

    Science.gov (United States)

    Kuno, Y.; Inoue, N.; Senzaki, M.

    2009-03-01

    Corresponding to the world nuclear security concerns, future nuclear fuel cycle (NFC) should have high proliferation-resistance (PR) and physical protection (PP), while promotion of the peaceful use of the nuclear energy must not be inhibited. In order to accomplish nuclear non-proliferation from NFC, a few models of the well-PR systems should be developed so that international community can recognize them as worldwide norms. To find a good balance of 'safeguard-ability (so-called extrinsic measure or institutional barrier)' and 'impede-ability (intrinsic feature or technical barrier)' will come to be essential for NFC designers to optimize civilian nuclear technology with nuclear non-proliferation, although the advanced safeguards with high detectability can still play a dominant role for PR in the states complying with full institutional controls. Accomplishment of such goal in a good economic efficiency is a future key challenge.

  3. Nuclear proliferation-resistance and safeguards for future nuclear fuel cycle

    Energy Technology Data Exchange (ETDEWEB)

    Kuno, Y. [Japan Atomic Energy Agency (JAEA) Nuclear-Non-proliferation Science and Technology Centre (NPSTC), 2-4 Shirane Shirakata, Tokai-mura, Ibaraki, 319-1195 (Japan); University of Tokyo, Nuclear Engineering and Management, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)], E-mail: kuno.yusuke@jaea.go.jp; Inoue, N. [Japan Atomic Energy Agency (JAEA) Nuclear-Non-proliferation Science and Technology Centre (NPSTC), 2-4 Shirane Shirakata, Tokai-mura, Ibaraki, 319-1195 (Japan); University of Tokyo, Nuclear Engineering and Management, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan); Senzaki, M. [Japan Atomic Energy Agency (JAEA) Nuclear-Non-proliferation Science and Technology Centre (NPSTC), 2-4 Shirane Shirakata, Tokai-mura, Ibaraki, 319-1195 (Japan)

    2009-03-15

    Corresponding to the world nuclear security concerns, future nuclear fuel cycle (NFC) should have high proliferation-resistance (PR) and physical protection (PP), while promotion of the peaceful use of the nuclear energy must not be inhibited. In order to accomplish nuclear non-proliferation from NFC, a few models of the well-PR systems should be developed so that international community can recognize them as worldwide norms. To find a good balance of 'safeguard-ability (so-called extrinsic measure or institutional barrier)' and 'impede-ability (intrinsic feature or technical barrier)' will come to be essential for NFC designers to optimize civilian nuclear technology with nuclear non-proliferation, although the advanced safeguards with high detectability can still play a dominant role for PR in the states complying with full institutional controls. Accomplishment of such goal in a good economic efficiency is a future key challenge.

  4. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, Brandon M.; Leix, Kyle Alexander [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ji, Yajing [Department of Biomedical Science and Medicine, Michigan State University, East Lansing, MI 48824 (United States); Glaves, Richard Samuel Elliot [Department of Biology, Central Michigan University, Mount Pleasant, MI 48859 (United States); Ash, David E. [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States); Mohanty, Dillip K., E-mail: Mohan1dk@cmich.edu [Department of Chemistry, Central Michigan University, Mount Pleasant, MI 48859 (United States)

    2014-07-18

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well.

  5. Slow and sustained nitric oxide releasing compounds inhibit multipotent vascular stem cell proliferation and differentiation without causing cell death

    International Nuclear Information System (INIS)

    Curtis, Brandon M.; Leix, Kyle Alexander; Ji, Yajing; Glaves, Richard Samuel Elliot; Ash, David E.; Mohanty, Dillip K.

    2014-01-01

    Highlights: • Multipotent vascular stem cells (MVSCs) proliferate and differentiate. • Nitric oxide inhibits proliferation of MVSCs. • Nitric oxide inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs). • Smooth muscle cells (SMCs) neither de-differentiate nor proliferate. - Abstract: Atherosclerosis is the leading cause of cerebral and myocardial infarction. It is believed that neointimal growth common in the later stages of atherosclerosis is a result of vascular smooth muscle cell (SMC) de-differentiation in response to endothelial injury. However, the claims of the SMC de-differentiation theory have not been substantiated by monitoring the fate of mature SMCs in response to such injuries. A recent study suggests that atherosclerosis is a consequence of multipotent vascular stem cell (MVSC) differentiation. Nitric oxide (NO) is a well-known mediator against atherosclerosis, in part because of its inhibitory effect on SMC proliferation. Using three different NO-donors, we have investigated the effects of NO on MVSC proliferation. Results indicate that NO inhibits MVSC proliferation in a concentration dependent manner. A slow and sustained delivery of NO proved to inhibit proliferation without causing cell death. On the other hand, larger, single-burst NO concentrations, inhibits proliferation, with concurrent significant cell death. Furthermore, our results indicate that endogenously produced NO inhibits MVSC differentiation to mesenchymal-like stem cells (MSCs) and subsequently to SMC as well

  6. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Walpen, Thomas; Kalus, Ina [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Schwaller, Juerg [Department of Biomedicine, University of Basel, 4031 Basel (Switzerland); Peier, Martin A. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Battegay, Edouard J. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland); Humar, Rok, E-mail: Rok.Humar@usz.ch [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation

  7. Assessment of proliferation resistances of aqueous reprocessing techniques using the TOPS methodology

    International Nuclear Information System (INIS)

    Åberg Lindell, M.; Grape, S.; Håkansson, A.; Jacobsson Svärd, S.

    2013-01-01

    Highlights: • Proliferation resistances of three possible LFR fuel cycles are assessed. • The TOPS methodology has been chosen for the PR assessment. • Reactor operation, reprocessing and fuel fabrication are examined. • Purex, Ganex, and a combination of Purex, Diamex and Sanex, are compared. • The safeguards analysis speaks in favor of Ganex as opposed to the Purex process. - Abstract: The aim of this study is to assess and compare the proliferation resistances (PR) of three possible Generation IV lead-cooled fast reactor fuel cycles, involving the reprocessing techniques Purex, Ganex and a combination of Purex, Diamex and Sanex, respectively. The examined fuel cycle stages are reactor operation, reprocessing and fuel fabrication. The TOPS methodology has been chosen for the PR assessment, and the only threat studied is the case where a technically advanced state diverts nuclear material covertly. According to the TOPS methodology, the facilities have been divided into segments, here roughly representing the different forms of nuclear material occurring in each examined fuel cycle stage. For each segment, various proliferation barriers have been assessed. The results make it possible to pinpoint where the facilities can be improved. The results show that the proliferation resistance of a fuel cycle involving recycling of minor actinides is higher than for the traditional Purex reprocessing cycle. Furthermore, for the purpose of nuclear safeguards, group actinide extraction should be preferred over reprocessing options where pure plutonium streams occur. This is due to the fact that a solution containing minor actinides is less attractive to a proliferator than a pure Pu solution. Thus, the safeguards analysis speaks in favor of Ganex as opposed to the Purex process

  8. Low-decontamination approach to a proliferation-resistant fuel cycle

    International Nuclear Information System (INIS)

    Asquith, J.G.; Grantham, L.F.

    1978-01-01

    To prevent the diversion of nuclear material from power production to weapon production either by a nation or by clandestine groups within a nation, the nuclear fuel cycle must be proliferation-resistant and safeguarded. Potentially proliferation-resistant and safeguarded fuel cycles based on low-decontamination pyroreprocessing have been developed for the light water reactor (LWR), fast breeder reactor (FBR), and FBR-LWR combination. The major penalty for recycling fission products to the LWR is that fuel enrichment must be somewhat greater to overcome parasitic fission product absorption of neutrons. In the FBR, the major penalty is a slight reduction in breeding ratio due to the displacement of fertile material by fission products. Preliminary cost analysis indicates that these fuel cycles are economically competitive with fuel cycles using conventional reprocessing or those using virgin uranium if spent fuel storage costs are considered

  9. Denaturing of plutonium by transmutation of minor-actinides for enhancement of proliferation resistance

    International Nuclear Information System (INIS)

    Sagara, Hiroshi; Saito, Masaki; Peryoga, Yoga; Ezoubtchenko, Alexey; Takivayev, Alan

    2005-01-01

    Feasibility study for the plutonium denaturing by utilizing minor-actinide transmutation in light water reactors has been performed. And the intrinsic feature of proliferation resistance of plutonium has been discussed based on IAEA's publication and Kessler's proposal. The analytical results show that not only 238 Pu but also other plutonium isotopes with even-mass-number have very important role for denaturing of plutonium due to their relatively large critical mass and noticeably high spontaneous fission neutron generation. With the change of the minor-actinide doping ratio in U-Pu mix oxide fuel and moderator to fuel ratio, it is found that the reactor-grade plutonium from conventional light water reactors can be denatured to satisfy the proliferation resistance criterion based on the Kessler's proposal but not to be sufficient for the criterion based on IAEA's publication. It has been also confirmed that all the safety coefficients take negative value throughout the irradiation. (author)

  10. A Modified Nitride-Based Fuel for Long Core Life and Proliferation Resistance

    International Nuclear Information System (INIS)

    Ebbinghaus, B; Choi, J; Meier, T

    2003-01-01

    A modified nitride-based uranium fuel to support the small, secured, transportable, and autonomous reactor (SSTAR) concept is initiated at Lawrence Livermore National laboratory (LLNL). This project centers on the evaluation of modified uranium nitride fuels imbedded with other inert (e.g. ZrN), neutron-absorbing (e.g. HfN) , or breeding (e.g. ThN) nitrides to enhance the fuel properties to achieve long core life with a compact reactor design. A long-life fuel could minimize the need for on-site refueling and spent-fuel storage. As a result, it could significantly improve the proliferation resistance of the reactor/fuel systems. This paper discusses the potential benefits and detriments of modified nitride-based fuels using the criteria of compactness, long-life, proliferation resistance, fuel safety, and waste management. Benefits and detriments are then considered in recommending a select set of compositions for further study

  11. Framework for Proliferation Resistance and Physical Protection for Nonproliferation Impact Assessments

    International Nuclear Information System (INIS)

    Bari, R.

    2008-01-01

    This report describes a framework for proliferation resistance and physical protection evaluation for the fuel cycle systems envisioned in the expansion of nuclear power for electricity generation. The methodology is based on an approach developed as part of the Generation IV technical evaluation framework and on a qualitative evaluation approach to policy factors similar to those that were introduced in previous Nonproliferation Impact Assessments performed by DOE

  12. Very High-Temperature Reactor (VHTR) Proliferation Resistance and Physical Protection (PR and PP)

    International Nuclear Information System (INIS)

    Moses, David Lewis

    2011-01-01

    This report documents the detailed background information that has been compiled to support the preparation of a much shorter white paper on the design features and fuel cycles of Very High-Temperature Reactors (VHTRs), including the proposed Next-Generation Nuclear Plant (NGNP), to identify the important proliferation resistance and physical protection (PR and PP) aspects of the proposed concepts. The shorter white paper derived from the information in this report was prepared for the Department of Energy Office of Nuclear Science and Technology for the Generation IV International Forum (GIF) VHTR Systems Steering Committee (SSC) as input to the GIF Proliferation Resistance and Physical Protection Working Group (PR and PPWG) (http://www.gen-4.org/Technology/horizontal/proliferation.htm). The short white paper was edited by the GIF VHTR SCC to address their concerns and thus may differ from the information presented in this supporting report. The GIF PR and PPWG will use the derived white paper based on this report along with other white papers on the six alternative Generation IV design concepts (http://www.gen-4.org/Technology/systems/index.htm) to employ an evaluation methodology that can be applied and will evolve from the earliest stages of design. This methodology will guide system designers, program policy makers, and external stakeholders in evaluating the response of each system, to determine each system's resistance to proliferation threats and robustness against sabotage and terrorism threats, and thereby guide future international cooperation on ensuring safeguards in the deployment of the Generation IV systems. The format and content of this report is that specified in a template prepared by the GIF PR and PPWG. Other than the level of detail, the key exception to the specified template format is the addition of Appendix C to document the history and status of coated-particle fuel reprocessing technologies, which fuel reprocessing technologies have yet

  13. Neutronic simulation calculations to assess the proliferation resistance of nuclear technologies; Neutronenphysikalische Simulationsrechnungen zur Proliferationsresistenz nuklearer Technologien

    Energy Technology Data Exchange (ETDEWEB)

    Englert, Matthias

    2009-07-13

    This thesis investigates the proliferation resistance of nuclear technologies on the basis of three case studies. After a brief description of the concept of proliferation resistance the utilized computer codes and methods are presented. The first case study investigates the potential of monolithic fuel for the conversion of one-fuel-element high-flux research reactors from highly enriched to low enriched uranium using the example of the german research reactor FRM-II. The second case study assesses the proliferation potential of future tokamak based fusion reactors by using neutronic simulations of a possible plutonium production. The third example investigates the proliferation potential of spallation neutron sources to produce nuclear weapon relevant material and the proliferation resistance of such facilities. (orig.)

  14. Methodology for proliferation resistance and physical protection of Generation IV nuclear energy systems

    International Nuclear Information System (INIS)

    Bari, R.; Peterson, P.; Nishimura, R.; Roglans-Ribas, J.

    2005-01-01

    Enhanced proliferation resistance and physical protection (PR and PP) is one of the technology goals for advanced nuclear concepts. Under the auspices of the Generation IV International Forum an international experts group has been chartered to develop an evaluation methodology for PR and PP. This methodology will permit an objective PR and PP comparison between alternative nuclear systems and support design optimization to enhance robustness against proliferation, theft and sabotage. The assessment framework consists of identifying the threats to be considered, defining the PR and PP measures required to evaluate the resistance of a nuclear system to proliferation, theft or sabotage, and establishing quantitative methods to evaluate the proposed measures. The defined PR and PP measures are based on the design of the system (e.g., materials, processes, facilities), and institutional measures (e.g., safeguards, access control). The assessment methodology uses analysis of pathways' with respect to specific threats to determine the PR and PP measures. Analysis requires definition of the threats (i.e. objective, capability, strategy), decomposition of the system into its relevant elements (e.g., reactor core, fuel recycle facility, fuel storage), and identification of targets. (author)

  15. Methodology Development and Applications of Proliferation Resistance and Physical Protection Evaluation

    International Nuclear Information System (INIS)

    Bari, R.A.; Peterson, P.F.; Therios, I.U.; Whitlock, J.J.

    2010-01-01

    We present an overview of the program on the evaluation methodology for proliferation resistance and physical protection (PR and PP) of advanced nuclear energy systems (NESs) sponsored by the Generation IV International Forum (GIF). For a proposed NES design, the methodology defines a set of challenges, analyzes system response to these challenges, and assesses outcomes. The challenges to the NES are the threats posed by potential actors (proliferant States or sub-national adversaries). The characteristics of Generation IV systems, both technical and institutional, are used to evaluate the response of the system and to determine its resistance against proliferation threats and robustness against sabotage and terrorism threats. The outcomes of the system response are expressed in terms of a set of measures, which are the high-level PR and PP characteristics of the NES. The methodology is organized to allow evaluations to be performed at the earliest stages of system design and to become more detailed and more representative as the design progresses. It can thus be used to enable a program in safeguards by design or to enhance the conceptual design process of an NES with regard to intrinsic features for PR and PP.

  16. Multi-component Self-Consistent Nuclear Energy System: On proliferation resistance aspect

    International Nuclear Information System (INIS)

    Shmelev, A.; Saito, M; Artisyuk, V.

    2000-01-01

    Self-Consistent Nuclear Energy System (SCNES) that simultaneously meets four requirements: energy production, fuel production, burning of radionuclides and safety is targeted at harmonization of nuclear energy technology with human environment. The main bulk of SCNES studies focus on a potential of fast reactor (FR) in generating neutron excess to keep suitable neutron balance. Proliferation resistance was implicitly anticipated in a fuel cycle with co-processing of Pu, minor actinides (MA) and some relatively short-lived fission products (FP). In a contrast to such a mono-component system, the present paper advertises advantage of incorporating accelerator and fusion driven neutron sources which could drastically improve characteristics of nuclear waste incineration. What important is that they could help in creating advanced Np and Pa containing fuels with double protection against uncontrolled proliferation. The first level of protection deals with possibility to approach long life core (LLC) in fission reactors. Extending the core life-time to reactor-time is beneficial from the proliferation resistance viewpoint since LLC would not necessarily require fuel management at energy producing site, with potential advantage of being moved to vendor site for spent fuel refabrication. Second level is provided by the presence of substantial amounts of 238 Pu and 232 U in these fuels that makes fissile nuclides in them isotopically protected. All this reveals an important advantage of a multi-component SCNES that could draw in developing countries without elaborated technological infrastructure. (author)

  17. DEVELOPMENT OF A METHODOLOGY TO ASSESS PROLIFERATION RESISTANCE AND PHYSICAL PROTECTION FOR GENERATION IV SYSTEMS

    International Nuclear Information System (INIS)

    Nishimura, R.; Bari, R.; Peterson, P.; Roglans-Ribas, J.; Kalenchuk, D.

    2004-01-01

    Enhanced proliferation resistance and physical protection (PR and PP) is one of the technology goals for advanced nuclear concepts, such as Generation IV systems. Under the auspices of the Generation IV International Forum, the Office of Nuclear Energy, Science and Technology of the U.S. DOE, the Office of Nonproliferation Policy of the National Nuclear Security Administration, and participating organizations from six other countries are sponsoring an international working group to develop an evaluation methodology for PR and PP. This methodology will permit an objective PR and PP comparison between alternative nuclear systems (e.g., different reactor types or fuel cycles) and support design optimization to enhance robustness against proliferation, theft and sabotage. The paper summarizes the proposed assessment methodology including the assessment framework, measures used to express the PR and PP characteristics of the system, threat definition, system element and target identification, pathway identification and analysis, and estimation of the measures

  18. Enzalutamide inhibits proliferation of gemcitabine-resistant bladder cancer cells with increased androgen receptor expression.

    Science.gov (United States)

    Kameyama, Koji; Horie, Kengo; Mizutani, Kosuke; Kato, Taku; Fujita, Yasunori; Kawakami, Kyojiro; Kojima, Toshio; Miyazaki, Tatsuhiko; Deguchi, Takashi; Ito, Masafumi

    2017-01-01

    Advanced bladder cancer is treated mainly with gemcitabine and cisplatin, but most patients eventually become resistance. Androgen receptor (AR) signaling has been implicated in bladder cancer as well as other types of cancer including prostate cancer. In this study, we investigated the expression and role of AR in gemcitabine-resistant bladder cancer cells and also the potential of enzalutamide, an AR inhibitor, as a therapeutic for the chemoresistance. First of all, we established gemcitabine-resistant T24 cells (T24GR) from T24 bladder cancer cells and performed gene expression profiling. Microarray analysis revealed upregulation of AR expression in T24GR cells compared with T24 cells. AR mRNA and protein expression was confirmed to be increased in T24GR cells, respectively, by quantitative RT-PCR and western blot analysis, which was associated with more potent AR transcriptional activity as measured by luciferase reporter assay. The copy number of AR gene in T24GR cells determined by PCR was twice as many as that of T24 cells. AR silencing by siRNA transfection resulted in inhibition of proliferation of T24GR cells. Cell culture in charcoal-stripped serum and treatment with enzalutamide inhibited growth of T24GR cells, which was accompanied by cell cycle arrest. AR transcriptional activity was found to be reduced in T24GR cells by enzalutamide treatment. Lastly, enzalutamide also inhibited cell proliferation of HTB5 bladder cancer cells that express AR and possess intrinsic resistance to gemcitabine. Our results suggest that enzalutamide may have the potential to treat patients with advanced gemcitabine-resistant bladder cancer with increased AR expression.

  19. Proliferation resistance of a hypothetical sodium fast reactor under an assumed breakout scenario

    Energy Technology Data Exchange (ETDEWEB)

    Whitlock, Jeremy [Non-Proliferation and Safeguards, AECL Chalk River Laboratories, Stn. 91, Chalk River, Ontario, K0J 1J0 (Canada); Inoue, Naoko; Senzaki, Masao [Japan Atomic Energy Agency - JAEA (Japan); Bley, Dennis [Buttonwood Consulting Inc., Oakton, VA (United States); Wonder, Ed [National Nuclear Security Administration, Department of Energy (United States)

    2009-06-15

    The Proliferation Resistance and Physical Protection (PR and PP) Working Group of the Generation IV International Forum (GIF) conducted a high-level pathway analysis of a hypothetical sodium fast reactor and integral fuel processing facility (called collectively the 'Example Sodium Fast Reactor' or ESFR), as a test of the effectiveness of its analysis methodology. From a common set of assumed host-state capabilities and objectives, a number of threat scenarios emerge (Concealed Diversion, Concealed Misuse, Breakout or Overt Misuse, and Theft/Sabotage). This paper presents the results of the analysis based on the Breakout scenario. A distinguishing aspect of Breakout scenario consideration concerns the optimal use of the time from breakout to weapons readiness, which is related to the Proliferation Time measure. The goal of analyzing the breakout scenario was therefore to complement other analyses involving the Concealed Misuse and Diversion scenarios by exploring the minimum post-breakout time to weapons readiness. Four target strategies were chosen for analysis: (1) Diversion of LEU feed material at front-end of the ESFR facility; (2) Misuse of the reactor facility to irradiate fertile material; (3) Misuse of the reactor facility to irradiate material in the in-core fuel storage basket; and (4) Misuse of the fuel processing facility to higher-purity TRU. The investigation identified several general 'sub-strategies' within the Breakout scenario, dependent upon the aggressiveness with which a State pursues its intent to break out (including its aversion to the risk of detection). The sub-strategy chosen by a proliferant state will affect both the time available and potential complexity for proliferation activities. The sub-strategy chosen is itself affected by political factors (foreign relations agenda of state, probability of external intervention after breakout, external dependence of proliferant state's supply chain, etc.) These factors

  20. Activated STAT5 Confers Resistance to Intestinal Injury by Increasing Intestinal Stem Cell Proliferation and Regeneration

    Directory of Open Access Journals (Sweden)

    Shila Gilbert

    2015-02-01

    Full Text Available Intestinal epithelial stem cells (IESCs control the intestinal homeostatic response to inflammation and regeneration. The underlying mechanisms are unclear. Cytokine-STAT5 signaling regulates intestinal epithelial homeostasis and responses to injury. We link STAT5 signaling to IESC replenishment upon injury by depletion or activation of Stat5 transcription factor. We found that depletion of Stat5 led to deregulation of IESC marker expression and decreased LGR5+ IESC proliferation. STAT5-deficient mice exhibited worse intestinal histology and impaired crypt regeneration after γ-irradiation. We generated a transgenic mouse model with inducible expression of constitutively active Stat5. In contrast to Stat5 depletion, activation of STAT5 increased IESC proliferation, accelerated crypt regeneration, and conferred resistance to intestinal injury. Furthermore, ectopic activation of STAT5 in mouse or human stem cells promoted LGR5+ IESC self-renewal. Accordingly, STAT5 promotes IESC proliferation and regeneration to mitigate intestinal inflammation. STAT5 is a functional therapeutic target to improve the IESC regenerative response to gut injury.

  1. Very High-Temperature Reactor (VHTR) Proliferation Resistance and Physical Protection (PR&PP)

    Energy Technology Data Exchange (ETDEWEB)

    Moses, David Lewis [ORNL

    2011-10-01

    This report documents the detailed background information that has been compiled to support the preparation of a much shorter white paper on the design features and fuel cycles of Very High-Temperature Reactors (VHTRs), including the proposed Next-Generation Nuclear Plant (NGNP), to identify the important proliferation resistance and physical protection (PR&PP) aspects of the proposed concepts. The shorter white paper derived from the information in this report was prepared for the Department of Energy Office of Nuclear Science and Technology for the Generation IV International Forum (GIF) VHTR Systems Steering Committee (SSC) as input to the GIF Proliferation Resistance and Physical Protection Working Group (PR&PPWG) (http://www.gen-4.org/Technology/horizontal/proliferation.htm). The short white paper was edited by the GIF VHTR SCC to address their concerns and thus may differ from the information presented in this supporting report. The GIF PR&PPWG will use the derived white paper based on this report along with other white papers on the six alternative Generation IV design concepts (http://www.gen-4.org/Technology/systems/index.htm) to employ an evaluation methodology that can be applied and will evolve from the earliest stages of design. This methodology will guide system designers, program policy makers, and external stakeholders in evaluating the response of each system, to determine each system's resistance to proliferation threats and robustness against sabotage and terrorism threats, and thereby guide future international cooperation on ensuring safeguards in the deployment of the Generation IV systems. The format and content of this report is that specified in a template prepared by the GIF PR&PPWG. Other than the level of detail, the key exception to the specified template format is the addition of Appendix C to document the history and status of coated-particle fuel reprocessing technologies, which fuel reprocessing technologies have yet to be

  2. Update of the INPRO Collaborative Project, Proliferation Resistance and Safeguard ability Assessment (Prosta) Tools

    Energy Technology Data Exchange (ETDEWEB)

    Chang, H. L.; Kwon, E. H.; Ahn, S. K.; Ko, W. I.; Kim, H. D. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-10-15

    The objectives of the INPRO Collaborative Project, Proliferation Resistance and Safeguard ability Assessment (PROSA) Tools are to make the INPRO proliferation resistance (PR) assessment methodology simpler and easier to use, to allow for different users and depths of analysis, to demonstrate the value and its usefulness of the refined assessment methodology to potential users, through a test with a reference case, and to provide input to a revision of the INPRO PR assessment manual. A summary of the project is described herein, including the procedure of PR assessment process and a case study using a SFR metal fuel manufacturing facility (SFMF) which is currently in the conceptual design phase at KAERI. The PROSA process with questionnaire approach is simpler and easier to perform that the original INPRO PR methodology with qualitative scale from 'weak' to 'very strong' to be determined by expert judgment. The PROSA process can be applied from the early stage of design showing the relationship of PR assessment to the SBD process.

  3. PPARγ1 phosphorylation enhances proliferation and drug resistance in human fibrosarcoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Xiaojuan; Shu, Yuxin; Niu, Zhiyuan; Zheng, Wei; Wu, Haochen [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Lu, Yan, E-mail: luyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Shen, Pingping, E-mail: ppshen@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Model Animal Research Center (MARC), Nanjing University, Nanjing (China)

    2014-03-10

    Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21{sup Waf1/Cip1} and p27{sup Kip1} descended in PPARγ1{sup S84D} stable HT1080 cell, whereas the expression of p18{sup INK4C} was not changed. Moreover, compared to the PPARγ1{sup S84A}, PPARγ1{sup S84D} up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs. - Highlights: • Phosphorylation attenuates PPARγ1 transcriptional activity. • Phosphorylated PPARγ1 promotes HT1080 cells proliferation. • PPARγ1 phosphorylation regulates cell cycle by mediating expression of cell cycle regulators. • PPARγ1 phosphorylation reduces sensitivity to agonist and anticancer drug. • Our findings establish PPARγ1 phosphorylation as a critical event in HT1080

  4. Prevalence and proliferation of antibiotic resistance genes in two municipal wastewater treatment plants.

    Science.gov (United States)

    Mao, Daqing; Yu, Shuai; Rysz, Michal; Luo, Yi; Yang, Fengxia; Li, Fengxiang; Hou, Jie; Mu, Quanhua; Alvarez, P J J

    2015-11-15

    The propagation of antibiotic resistance genes (ARGs) is an emerging health concern worldwide. Thus, it is important to understand and mitigate their occurrence in different systems. In this study, 30 ARGs that confer resistance to tetracyclines, sulfonamides, quinolones or macrolides were detected in two activated sludge wastewater treatment plants (WWTPs) in northern China. Bacteria harboring ARGs persisted through all treatment units, and survived disinfection by chlorination in greater percentages than total Bacteria (assessed by 16S rRNA genes). Although the absolute abundances of ARGs were reduced from the raw influent to the effluent by 89.0%-99.8%, considerable ARG levels [(1.0 ± 0.2) × 10(3) to (9.5 ± 1.8) × 10(5) copies/mL)] were found in WWTP effluent samples. ARGs were concentrated in the waste sludge (through settling of bacteria and sludge dewatering) at (1.5 ± 2.3) × 10(9) to (2.2 ± 2.8) × 10(11) copies/g dry weight. Twelve ARGs (tetA, tetB, tetE, tetG, tetH, tetS, tetT, tetX, sul1, sul2, qnrB, ermC) were discharged through the dewatered sludge and plant effluent at higher rates than influent values, indicating overall proliferation of resistant bacteria. Significant antibiotic concentrations (2%-50% of raw influent concentrations) remained throughout all treatment units. This apparently contributed selective pressure for ARG replication since the relative abundance of resistant bacteria (assessed by ARG/16S rRNA gene ratios) was significantly correlated to the corresponding effluent antibiotic concentrations. Similarly, the concentrations of various heavy metals (which induce a similar bacterial resistance mechanism as antibiotics - efflux pumps) were also correlated to the enrichment of some ARGs. Thus, curtailing the release of antibiotics and heavy metals to sewage systems (or enhancing their removal in pre-treatment units) may alleviate their selective pressure and mitigate ARG proliferation in WWTPs. Copyright © 2015 Elsevier Ltd. All

  5. Evaluating the attractiveness of nuclear material for proliferation-resistance and nuclear security

    International Nuclear Information System (INIS)

    Choi, Jor-Shan; Ikegame, Kou; Kuno, Yusuke

    2011-01-01

    The attractiveness of nuclear material, defined as a function of the isotopic composition of the nuclear material in formulas expressing the material's intrinsic properties, is of considerably debate in recent developments of proliferation-resistance measures of a nuclear energy system. A reason for such debate arises from the fact that the concept of nuclear material attractiveness can be confusing because the desirability of a material for nuclear explosive use depends on many tangible and intangible factors including the intent and capability of the adversary. In addition, a material that is unattractive to an advanced nation (in the case of proliferation) may be very attractive to a terrorist (in the case of physical protection and nuclear security). Hence, the concept of 'Nuclear Material Attractiveness' for different nuclear materials must be considered in the context of safeguards and security. The development of a ranking scheme on the attractiveness of nuclear materials could be a useful concept to start-off the strategies for safeguards and security on a new footing (i.e., why and how nuclear material is attractive, and what are the quantifiable basis). Japan may benefit from such concept regarding the attractiveness of nuclear materials when recovering nuclear materials from the damaged cores in Fukushima because safety, security, and safeguards (3S) would be a prominent consideration for the recovery operation, and it would be the first time such operation is performed in a non-nuclear weapons state. (author)

  6. The status of proliferation resistance evaluation methodology development in GEN IV international forum

    International Nuclear Information System (INIS)

    Inoue, Naoko; Kawakubo, Yoko; Seya, Michio; Suzuki, Mitsutoshi; Kuno, Yusuke; Senzaki, Masao

    2010-01-01

    The Generation IV Nuclear Energy Systems International Forum (GIF) Proliferation Resistance and Physical Protection Working Group (PR and PP WG) was established in December 2002 in order to develop the PR and PP evaluation methodology for GEN IV nuclear energy systems. The methodology has been studied and established by international consensus. The PR and PP WG activities include development of the measures and metrics; establishment of the framework of PR and PP evaluation, the demonstration study using Example Sodium Fast Reactor (ESFR), which included the development of three evaluation approaches; the Case Study using ESFR and four kinds of threat scenarios; the joint study with GIF System Steering Committees (SSCs) of the six reactor design concepts; and the harmonization study with the IAEA's International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). This paper reviews the status of GIF PR and PP studies and identifies the challenges and directions for applying the methodology to evaluate future nuclear energy systems in Japan. (author)

  7. The encapsulated nuclear heat source reactor for proliferation-resistant nuclear energy

    International Nuclear Information System (INIS)

    Brown, N.W.; Hossain, Q.; Carelli, M.D.; Conway, L.; Dzodzo, M.; Greenspan, E.; Saphier, D.

    2001-01-01

    The encapsulated nuclear heat source (ENHS) is a modular reactor that was selected by the 1999 DOE NERI program as a candidate ''Generation-IV'' reactor concept. It is a fast neutron spectrum reactor cooled by Pb-Bi using natural circulation. It is designed for passive load following, for high level of passive safety, and for 15 years without refueling. One of the unique features of the ENHS is that the fission-generated heat is transferred from the primary coolant to the secondary coolant across the reactor vessel wall by conduction-providing for an essentially sealed module that is easy to install and replace. Because the fuel is encapsulated within a heavy steel container throughout its life it provides a unique improvement to the proliferation resistance of the nuclear fuel cycle. This paper presents the innovative technology of the ENHS. (author)

  8. Containment and Surveillance and Physical Protection Updates for Proliferation Resistance Analysis Using PRAETOR

    International Nuclear Information System (INIS)

    Chirayath, S.; Charlton, W.; Elmore, R.

    2015-01-01

    The Proliferation Resistance Analysis and Evaluation Tool for Observed Risk (PRAETOR) software code assesses the proliferation resistance (PR) of nuclear fuel cycle (NFC) systems. The Nuclear Security Science and Policy Institute (NSSPI) at Texas A&M University developed PRAETOR based on the well-established multi-attribute utility analysis (MAUA) methodology. MAUA methods facilitate compiling multiple PR characteristics into tiered PRAETOR output PR metrics enabling easier decision making at the analyst, program manager, and policy maker levels. PRAETOR uses intrinsic and extrinsic PR attributes to evaluate NFC systems. The PRAETOR 1.0 code originally had 63 attribute inputs representing the NFC system. The attribute input values assigned by the user are mapped to a utility value between 0 and 1 using utility functions. Each attribute has an associated weight obtained through a survey. Larger PRAETOR utility values indicate higher NFC system PR. An updated version of PRAETOR (Version 2.0) added seven more attribute inputs representing the nuclear security PR aspects of: (1) physical protection systems (PPS) and (2) containment and surveillance (C&S). The applicability of PRAETOR is demonstrated through a set of case studies. Two cases of Pressurized Water Reactor (PWR)used fuel assemblies with different cooling times were considered in this paper: (a) non-cooled fuel assemblies, and (b) 30-year cooled fuel assemblies. The case studies consider the new PPS and C&S attributes with low and high utility values. The PR results for the case studies with the updated PRAETOR were compared with those without the PPS and C&S attributes. The new attributes increased overall PR value by about 10% for case (a) and decreased it by about 3% in case (b). The importance of adding new attributes capturing physical protection and containment & surveillance is established. (author)

  9. PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.

    Science.gov (United States)

    Pérès, Eléonore; Blin, Juliana; Ricci, Emiliano P; Artesi, Maria; Hahaut, Vincent; Van den Broeke, Anne; Corbin, Antoine; Gazzolo, Louis; Ratner, Lee; Jalinot, Pierre; Duc Dodon, Madeleine

    2018-03-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus. We observed that the frequency of CD4+ activated T-cells in the peripheral blood and in the spleen was significantly higher in WT than in ΔPBM hu-mice. Likewise, human T-cells collected from WT hu-mice and cultivated in vitro in presence of interleukin-2 were proliferating at a higher level than those from ΔPBM animals. We next examined the association of Tax with the Scribble PDZ protein, a prominent regulator of T-cell polarity, in human T-cells analyzed either after ex vivo isolation or after in vitro culture. We confirmed the interaction of Tax with Scribble only in T-cells from the WT hu-mice. This association correlated with the presence of both proteins in aggregates at the leading edge of the cells and with the formation of long actin filopods. Finally, data from a comparative genome-wide transcriptomic analysis suggested that the PBM-PDZ association is implicated in the expression of genes regulating proliferation, apoptosis and cytoskeletal organization. Collectively, our findings suggest that the Tax PBM is an auxiliary motif that contributes to the sustained growth of HTLV-1 infected T-cells in vivo and in vitro and is essential to T-cell immortalization.

  10. Assessment of Proliferation Resistance of Closed Nuclear Fuel Cycle System with Sodium Cooled Fast Reactors Using INPRO Evaluation Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young In; Hahn, Do Hee; Won, Byung Chool; Lee, Dong Uk

    2007-11-15

    Using the INPRO methodology, the proliferation resistance of an innovative nuclear energy system(INS) defined as a closed nuclear fuel cycle system consisting of KALIMER and pyroprocessing, has been assessed. Considering a very early development stage of the INS concept, the PR assessment is carried out based on intrinsic features, if required information and data are not available. The PR assessment of KALIMER and JSFR using the INPRO methodology affirmed that an adequate proliferation resistance has been achieved in both INSs CNFC-SFR, considering the assessor's progress and maturity of design development. KALIMER and JSFR are developed or being developed conforming to the targets and criteria defined for developing Gen IV nuclear reactor system. Based on these assessment results, proliferation resistance and physical protection(PR and PP) of KALIMER and JSFR are evaluated from the viewpoint of requirements for future nuclear fuel cycle system. The envisioned INSs CNFC-SFR rely on active plutonium management based on a closed fuel cycle, in which a fissile material is recycled in an integrated fuel cycle facility within proper safeguards. There is no isolated plutonium in the closed fuel cycle. The material remains continuously in a sequence of highly radioactive matrices within inaccessible facilities. The proliferation resistance assessment should be an ongoing analysis that keeps up with the progress and maturity of the design of Gen IV SFR.

  11. Assessment of Proliferation Resistance of Closed Nuclear Fuel Cycle System with Sodium Cooled Fast Reactors Using INPRO Evaluation Methodology

    International Nuclear Information System (INIS)

    Kim, Young In; Hahn, Do Hee; Won, Byung Chool; Lee, Dong Uk

    2007-11-01

    Using the INPRO methodology, the proliferation resistance of an innovative nuclear energy system(INS) defined as a closed nuclear fuel cycle system consisting of KALIMER and pyroprocessing, has been assessed. Considering a very early development stage of the INS concept, the PR assessment is carried out based on intrinsic features, if required information and data are not available. The PR assessment of KALIMER and JSFR using the INPRO methodology affirmed that an adequate proliferation resistance has been achieved in both INSs CNFC-SFR, considering the assessor's progress and maturity of design development. KALIMER and JSFR are developed or being developed conforming to the targets and criteria defined for developing Gen IV nuclear reactor system. Based on these assessment results, proliferation resistance and physical protection(PR and PP) of KALIMER and JSFR are evaluated from the viewpoint of requirements for future nuclear fuel cycle system. The envisioned INSs CNFC-SFR rely on active plutonium management based on a closed fuel cycle, in which a fissile material is recycled in an integrated fuel cycle facility within proper safeguards. There is no isolated plutonium in the closed fuel cycle. The material remains continuously in a sequence of highly radioactive matrices within inaccessible facilities. The proliferation resistance assessment should be an ongoing analysis that keeps up with the progress and maturity of the design of Gen IV SFR

  12. Methodology development for plutonium categorization and enhancement of proliferation resistance by P3 mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Saito, M.; Kimura, Y.; Sagara, H.; Han, C. Y. [Tokyo Institute of Technology, Tokyo (Japan); Koyama, S. [Japan Atomic Energy Agency, Ibaraki (Japan)

    2012-03-15

    'Protected Plutonium Production (P3)' has been proposed to enhance the proliferation resistance of plutonium by the transmutation of Minor Actinides (MA). For example, adding the small amount of Minor Actinides such as {sup 237}Np or {sup 241}Am with large neutron capture cross-section to the uranium fuel to enhance the production of {sup 238}Pu, which has high spontaneous fission neutron rate do deteriorate the quality of the nuclear weapon manufacture and maintenance technologically difficult, is very effective for improving the isotopic barrier for the proliferation of plutonium. To demonstrate the P3 mechanism experimentally, U samples with 2, 5 and 10% {sup 237}Np doping were irradiated in Advanced Thermal Reactor (ATR) of INL. The fuel test samples were removed from the core at 100, 200 and 300 effective full power days (EFPD), and then post irradiation examination was completed at Chemical Lab. in Idaho National Laboratory(INL). The theoretical results of P3 mechanism predict the experimental ones quite well. The evaluation function, 'Attractiveness', was introduced as the ratio of function of Rossi-alpha to the 'Technical Difficulties for Fission Explosive Device Use. 'Rossi-alpha defined as the ratio of super-criticality to prompt neutron lifetime is the meaningful feature of the explosive yield. The Technical Difficulties for Fission Explosive Device Use can be expressed by the function of specific decay heat , spontaneous fission neutron rate and radiation of plutonium metal. Original methodology to evaluate Attractiveness of Plutonium has been improved by considering the effect of the compression of Plutonium isotope and also pre-detonation probability due to spontaneous fission neutron ate, which was applied for the categorization of the plutonium from the conventional reactors and the innovative reactors based on P3 mechanism. In the present paper, the fundamentals of P3 mechanism, the experimental demonstration of P3

  13. Methodology development for plutonium categorization and enhancement of proliferation resistance by P3 mechanism

    International Nuclear Information System (INIS)

    Saito, M.; Kimura, Y.; Sagara, H.; Han, C. Y.; Koyama, S.

    2012-01-01

    'Protected Plutonium Production (P3)' has been proposed to enhance the proliferation resistance of plutonium by the transmutation of Minor Actinides (MA). For example, adding the small amount of Minor Actinides such as 237 Np or 241 Am with large neutron capture cross-section to the uranium fuel to enhance the production of 238 Pu, which has high spontaneous fission neutron rate do deteriorate the quality of the nuclear weapon manufacture and maintenance technologically difficult, is very effective for improving the isotopic barrier for the proliferation of plutonium. To demonstrate the P3 mechanism experimentally, U samples with 2, 5 and 10% 237 Np doping were irradiated in Advanced Thermal Reactor (ATR) of INL. The fuel test samples were removed from the core at 100, 200 and 300 effective full power days (EFPD), and then post irradiation examination was completed at Chemical Lab. in Idaho National Laboratory(INL). The theoretical results of P3 mechanism predict the experimental ones quite well. The evaluation function, 'Attractiveness', was introduced as the ratio of function of Rossi-alpha to the 'Technical Difficulties for Fission Explosive Device Use. 'Rossi-alpha defined as the ratio of super-criticality to prompt neutron lifetime is the meaningful feature of the explosive yield. The Technical Difficulties for Fission Explosive Device Use can be expressed by the function of specific decay heat , spontaneous fission neutron rate and radiation of plutonium metal. Original methodology to evaluate Attractiveness of Plutonium has been improved by considering the effect of the compression of Plutonium isotope and also pre-detonation probability due to spontaneous fission neutron ate, which was applied for the categorization of the plutonium from the conventional reactors and the innovative reactors based on P3 mechanism. In the present paper, the fundamentals of P3 mechanism, the experimental demonstration of P3 mechanism in ATR of INL and the methodology

  14. Status of the Gen-IV Proliferation Resistance and Physical Protection (PRPP) Evaluation Methodology

    International Nuclear Information System (INIS)

    Whitlock, J.; Bari, R.; Peterson, P.; Padoani, F.; Cojazzi, G.G.M.; Renda, G.; ); Cazalet, J.; Haas, E.; Hori, K.; Kawakubo, Y.; Chang, S.; Kim, H.; Kwon, E.-H.; Yoo, H.; Chebeskov, A.; Pshakin, G.; Pilat, J.F.; Therios, I.; Bertel, E.

    2015-01-01

    Methodologies have been developed within the Generation IV International Forum (GIF) to support the assessment and improvement of system performance in the areas safeguards, security, economics and safety. Of these four areas, safeguards and security are the subjects of the GIF working group on Proliferation Resistance and Physical Protection (PRPP). Since the PRPP methodology (now at Revision 6) represents a mature, generic, and comprehensive evaluation approach, and is freely available on the GIF public website, several non-GIF technical groups have chosen to utilize the PRPP methodology for their own goals. Indeed, the results of the evaluations performed with the methodology are intended for three types of generic users: system designers, programme policy makers, and external stakeholders. The PRPP Working Group developed the methodology through a series of demonstration and case studies. In addition, over the past few years various national and international groups have applied the methodology to inform nuclear energy system designs, as well as to support the development of approaches to advanced safeguards. A number of international workshops have also been held which have introduced the methodology to design groups and other stakeholders. In this paper we summarize the technical progress and accomplishments of the PRPP evaluation methodology, including applications outside GIF, and we outline the PRPP methodology's relationship with the IAEA's INPRO methodology. Current challenges with the efficient implementation of the methodology are outlined, along with our path forward for increasing its accessibility to a broader stakeholder audience - including supporting the next generation of skilled professionals in the nuclear non-proliferation field. (author)

  15. CANDLE reactor: an option for simple, safe, high nuclear proliferation resistant , small waste and efficient fuel use reactor

    International Nuclear Information System (INIS)

    Sekimoto, H.

    2010-01-01

    The innovative nuclear energy systems have been investigated intensively for long period in COE-INES program and CRINES activities in Tokyo Institute of Technology. Five requirements; sustainability, safety, waste, nuclear-proliferation, and economy; are considered as inevitable requirements for nuclear energy. Characteristics of small LBE cooled CANDLE fast reactor developed in this Institute are discussed for these requirements. It satisfies clearly four requirements; safety, nonproliferation and safeguard, less wastes and sustainability. For the remaining requirement, economy, a high potential to satisfy this requirement is also shown

  16. Utility of Social Modeling for Proliferation Assessment - Enhancing a Facility-Level Model for Proliferation Resistance Assessment of a Nuclear Enegry System

    Energy Technology Data Exchange (ETDEWEB)

    Coles, Garill A.; Brothers, Alan J.; Gastelum, Zoe N.; Olson, Jarrod; Thompson, Sandra E.

    2009-10-26

    The Utility of Social Modeling for Proliferation Assessment project (PL09-UtilSocial) investigates the use of social and cultural information to improve nuclear proliferation assessments, including nonproliferation assessments, Proliferation Resistance (PR) assessments, safeguards assessments, and other related studies. These assessments often use and create technical information about a host State and its posture towards proliferation, the vulnerability of a nuclear energy system (NES) to an undesired event, and the effectiveness of safeguards. This objective of this project is to find and integrate social and technical information by explicitly considering the role of cultural, social, and behavioral factors relevant to proliferation; and to describe and demonstrate if and how social science modeling has utility in proliferation assessment. This report describes a modeling approach and how it might be used to support a location-specific assessment of the PR assessment of a particular NES. The report demonstrates the use of social modeling to enhance an existing assessment process that relies on primarily technical factors. This effort builds on a literature review and preliminary assessment performed as the first stage of the project and compiled in PNNL-18438. [ T his report describes an effort to answer questions about whether it is possible to incorporate social modeling into a PR assessment in such a way that we can determine the effects of social factors on a primarily technical assessment. This report provides: 1. background information about relevant social factors literature; 2. background information about a particular PR assessment approach relevant to this particular demonstration; 3. a discussion of social modeling undertaken to find and characterize social factors that are relevant to the PR assessment of a nuclear facility in a specific location; 4. description of an enhancement concept that integrates social factors into an existing, technically

  17. Nuclear data for innovative reactors having persistent resistance to nuclear proliferation

    International Nuclear Information System (INIS)

    Yoshida, Tadashi; Hagura, Naoto; Toshinsky, Vladimir; Saito, Masaki

    2005-01-01

    The Protected Plutonium Production (P 3 ) project has been initiated in order to realize the proliferation-resistant plutonium. The first stage of this project is based on the idea to protect plutonium by 238 Pu generated from 237 Np doped in the fresh uranium fuel. Along with the burnup going on, the doped 237 Np is transmuted via 238 Np to 238 Pu, which is the intense neutron source of spontaneous fission (2.6x10 3 n/g/s). These neutrons will deteriorate the quality of the plutonium as the nuclear explosive material. In addition, high alpha-decay heat of 238 Pu (560 W/kg) makes the processes of the explosive fabrication and its maintenance technologically difficult. In this background we surveyed the status of nuclear data relevant to the P 3 -concept reactor design. The reliability of the capture cross section data for 237 Np and 238 Pu are far from satisfactory and more accurate experiments and evaluations are required. As fissions in these nuclides do not always play any decisive role in the P 3 concept LWR, we can be fairly tolerable about the uncertainty of the fission cross section data, but further study is needed. (author)

  18. Thermal-hydraulic development a small, simplified, proliferation-resistant reactor

    International Nuclear Information System (INIS)

    Farmer, M. T.; Hill, D. J.; Sienicki, J. J.; Spencer, B. W.; Wade, D. C.

    1999-01-01

    This paper addresses thermal-hydraulics related criteria and preliminary concepts for a small (300 MWt), proliferation-resistant, liquid-metal-cooled reactor system. A main objective is to assess what extent of simplification is achievable in the concepts with the primary purpose of regaining economic competitiveness. The approach investigated features lead-bismuth eutectic (LBE) and a low power density core for ultra-long core lifetime (goal 15 years) with cartridge core replacement at end of life. This potentially introduces extensive simplifications resulting in capital cost and operating cost savings including: (1) compact, modular, pool-type configuration for factory fabrication, (2) 100+% natural circulation heat transport with the possibility of eliminating the main coolant pumps, (3) steam generator modules immersed directly in the primary coolant pool for elimination of the intermediate heat transport system, and (4) elimination of on-site fuel handling and storage provisions including rotating plug. Stage 1 natural circulation model and results are presented. Results suggest that 100+% natural circulation heat transport is readily achievable using LBE coolant and the long-life cartridge core approach; moreover, it is achievable in a compact pool configuration considerably smaller than PRISM A (for overland transportability) and with peak cladding temperature within the existing database range for ferritic steel with oxide layer surface passivation. Stage 2 analysis follows iteration with core designers. Other thermal hydraulic investigations are underway addressing passive, auxiliary heat removal by air cooling of the reactor vessel and the effects of steam generator tube rupture

  19. Development status and potential program for development of proliferation-resistant molten-salt reactors

    International Nuclear Information System (INIS)

    Engel, J.R.; Bauman, H.F.; Dearing, J.F.; Grimes, W.R.; McCoy, H.E. Jr.

    1979-03-01

    Preliminary studies of existing and conceptual molten-salt reactor (MSR) designs have led to the identification of conceptual systems that are technologically attractive when operated with denatured uranium as the principal fissile fuel. These denatured MSRs would also have favorable resource-utilization characteristics and substantial resistance to proliferation of weapons-usable nuclear materials. The report presents a summary of the current status of technology and a discussion of the major technical areas of a possible base program to develop commercial denatured MSRs. The general areas treated are (1) reactor design and development, (2) safety and safety related technology, (3) fuel-coolant behavior and fuel processing, and (4) reactor materials. A substantial development effort could lead to authorization for construction of a molten-salt test reactor about 5 years after the start of the program and operation of the unit about 10 years later. A prototype commercial denatured MSR could be expected to begin operating 25 years from the start of the program. The postulated base program would extend over 32 years and would cost about $700 million (1978 dollars, unescalated). Additional costs to construct the MSTR, $600 million, and the prototype commercial plant, $1470 million, would bring the total program cost to about $2.8 billion. Additional allowances probably should be made to cover contingencies and incidental technology areas not explicitly treated in this preliminary review

  20. Development status and potential program for development of proliferation-resistant molten-salt reactors

    Energy Technology Data Exchange (ETDEWEB)

    Engel, J.R.; Bauman, H.F.; Dearing, J.F.; Grimes, W.R.; McCoy, H.E. Jr.

    1979-03-01

    Preliminary studies of existing and conceptual molten-salt reactor (MSR) designs have led to the identification of conceptual systems that are technologically attractive when operated with denatured uranium as the principal fissile fuel. These denatured MSRs would also have favorable resource-utilization characteristics and substantial resistance to proliferation of weapons-usable nuclear materials. The report presents a summary of the current status of technology and a discussion of the major technical areas of a possible base program to develop commercial denatured MSRs. The general areas treated are (1) reactor design and development, (2) safety and safety related technology, (3) fuel-coolant behavior and fuel processing, and (4) reactor materials. A substantial development effort could lead to authorization for construction of a molten-salt test reactor about 5 years after the start of the program and operation of the unit about 10 years later. A prototype commercial denatured MSR could be expected to begin operating 25 years from the start of the program. The postulated base program would extend over 32 years and would cost about $700 million (1978 dollars, unescalated). Additional costs to construct the MSTR, $600 million, and the prototype commercial plant, $1470 million, would bring the total program cost to about $2.8 billion. Additional allowances probably should be made to cover contingencies and incidental technology areas not explicitly treated in this preliminary review.

  1. PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice

    Science.gov (United States)

    Artesi, Maria; Jalinot, Pierre

    2018-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL), an aggressive malignant proliferation of activated CD4+ T lymphocytes. The viral Tax oncoprotein is critically involved in both HTLV-1-replication and T-cell proliferation, a prerequisite to the development of ATLL. In this study, we investigated the in vivo contribution of the Tax PDZ domain-binding motif (PBM) to the lymphoproliferative process. To that aim, we examined T-cell proliferation in humanized mice (hu-mice) carrying a human hemato-lymphoid system infected with either a wild type (WT) or a Tax PBM-deleted (ΔPBM) provirus. We observed that the frequency of CD4+ activated T-cells in the peripheral blood and in the spleen was significantly higher in WT than in ΔPBM hu-mice. Likewise, human T-cells collected from WT hu-mice and cultivated in vitro in presence of interleukin-2 were proliferating at a higher level than those from ΔPBM animals. We next examined the association of Tax with the Scribble PDZ protein, a prominent regulator of T-cell polarity, in human T-cells analyzed either after ex vivo isolation or after in vitro culture. We confirmed the interaction of Tax with Scribble only in T-cells from the WT hu-mice. This association correlated with the presence of both proteins in aggregates at the leading edge of the cells and with the formation of long actin filopods. Finally, data from a comparative genome-wide transcriptomic analysis suggested that the PBM-PDZ association is implicated in the expression of genes regulating proliferation, apoptosis and cytoskeletal organization. Collectively, our findings suggest that the Tax PBM is an auxiliary motif that contributes to the sustained growth of HTLV-1 infected T-cells in vivo and in vitro and is essential to T-cell immortalization. PMID:29566098

  2. Acute insulin resistance stimulates and insulin sensitization attenuates vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Cersosimo, Eugenio; Xu, Xiaojing; Upala, Sikarin; Triplitt, Curtis; Musi, Nicolas

    2014-08-01

    Differential activation/deactivation of insulin signaling, PI-3K and MAP-K pathways by high glucose and palmitate, with/out the insulin sensitizer pioglitazone (PIO), have been previously shown in vascular smooth muscle cells (VSMCs). To determine the biological impact of these molecular changes, we examined VSMC migration and proliferation ("M"&"P") patterns in similar conditions. VSMCs from healthy human coronary arteries were incubated in growth medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) ± palmitate (200 μmol/L) and ± PIO (8 μmol/L) for 5 h. "M"&"P" were assessed by: (1) polycarbonate membrane barrier with chemo-attractants and extended cell protrusions quantified by optical density (OD595 nm); (2) % change in radius area (2D Assay) using inverted microscopy images; and (3) cell viability assay expressed as cell absorbance (ABS) in media. "M" in 25 mmol/L glucose media increased by ~25% from baseline and % change in radius area rose from ~20% to ~30%. The addition of PIO was accompanied by a significant decrease in "M" from 0.25 ± 0.02 to 0.19 ± 0.02; a comparable decline from 0.25 ± 0.02 to 0.18 ± 0.02 was also seen with 25 mmol/L of glucose +200 μmol/L of palmitate. When PIO was coincubated with high glucose plus palmitate there was a 50% reduction in % change in radius. A ~10% increase in ABS, reflecting augmented "P" in media with 25 mmol/L glucose versus control was documented. The addition of PIO reduced ABS from 0.208 ± 0.03 to 0.183 ± 0.06. Both high glucose and palmitate showed ABS of ~0.140 ± 0.02, which decreased with PIO to ~0.120 ± 0.02, indicating "P" was reduced. These results confirm that high glucose and palmitate stimulate VSMCs migration and proliferation in vitro, which is attenuated by coincubation with the insulin sensitizer PIO. Although, we cannot ascertain whether these functional changes are coincident with the activation/deactivation of signal molecules, our findings are consistent with the

  3. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Tang, Yanping [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Wang, Jian [Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Yan, Zhongjie [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China); Xu, Ruxiang, E-mail: RuxiangXu@yahoo.com [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)

    2013-06-14

    Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3′UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

  4. SUSTAINABILITY OF INSECT RESISTANCE MANAGEMENT STRATEGIES FOR TRANSGENIC BT CORN

    Science.gov (United States)

    Increasing interest in the responsible management of technology in the industrial and agricultural sectors of the economy has been met through the development of broadly applicable tools to assess the "sustainability" of new technologies. An arena ripe for application of such ana...

  5. Endogenous growth factor stimulation of hemocyte proliferation induces resistance to Schistosoma mansoni challenge in the snail host.

    Science.gov (United States)

    Pila, Emmanuel A; Gordy, Michelle A; Phillips, Valerie K; Kabore, Alethe L; Rudko, Sydney P; Hanington, Patrick C

    2016-05-10

    Digenean trematodes are a large, complex group of parasitic flatworms that infect an incredible diversity of organisms, including humans. Larval development of most digeneans takes place within a snail (Gastropoda). Compatibility between snails and digeneans is often very specific, such that suitable snail hosts define the geographical ranges of diseases caused by these worms. The immune cells (hemocytes) of a snail are sentinels that act as a crucial barrier to infection by larval digeneans. Hemocytes coordinate a robust and specific immunological response, participating directly in parasite killing by encapsulating and clearing the infection. Hemocyte proliferation and differentiation are influenced by unknown digenean-specific exogenous factors. However, we know nothing about the endogenous control of hemocyte development in any gastropod model. Here, we identify and functionally characterize a progranulin [Biomphalaria glabrata granulin (BgGRN)] from the snail B. glabrata, a natural host for the human blood fluke Schistosoma mansoni Granulins are growth factors that drive proliferation of immune cells in organisms, spanning the animal kingdom. We demonstrate that BgGRN induces proliferation of B. glabrata hemocytes, and specifically drives the production of an adherent hemocyte subset that participates centrally in the anti-digenean defense response. Additionally, we demonstrate that susceptible B. glabrata snails can be made resistant to infection with S. mansoni by first inducing hemocyte proliferation with BgGRN. This marks the functional characterization of an endogenous growth factor of a gastropod mollusc, and provides direct evidence of gain of resistance in a snail-digenean infection model using a defined factor to induce snail resistance to infection.

  6. Calcium or resistant starch does not affect colonic epithelial cell proliferation throughout the colon in adenoma patients : A randomized controlled trial

    NARCIS (Netherlands)

    van Gorkom, Britta A P; Karrenbeld, Arend; van der Sluis, Tineke; Zwart, Nynke; van der Meer, Roelof; de Vries, Elisabeth G E; Kleibeuker, Jan H

    2002-01-01

    Patients with a history of sporadic adenomas have increased epithelial cell proliferative activity, an intermediate risk marker for colorectal cancer. Reduction of proliferation by dietary intervention may reflect a decreased colorectal cancer risk. To evaluate whether calcium or resistant starch

  7. Concept of the development of new type reactor and other nuclear technology in which nuclear-proliferation resistivity is taken into consideration

    International Nuclear Information System (INIS)

    Chang, Yoon I.

    2000-01-01

    As we start a new century in a new millennium, it is timely to look back at the last 50 years of nuclear energy development, and take a pause here to formulate the directions we need to take in the nuclear energy development for the next 50 years and beyond. The proliferation resistivity should be given a priority in the development of next-generation advanced reactor concepts, and there are three important principles to be considered in such efforts. The proliferation resistivity should be considered as a part of broader objectives, rather than a design goal by itself; the proliferation resistivity should be considered within the context of global institutional framework; and any technical proliferation resistivity features designed into the reactor system should be made intrinsic in nature. (author)

  8. Cyclodextrin-Modified Porous Silicon Nanoparticles for Efficient Sustained Drug Delivery and Proliferation Inhibition of Breast Cancer Cells.

    Science.gov (United States)

    Correia, Alexandra; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Almeida, Sérgio; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2015-10-21

    Over the past decade, the potential of polymeric structures has been investigated to overcome many limitations related to nanosized drug carriers by modulating their toxicity, cellular interactions, stability, and drug-release kinetics. In this study, we have developed a successful nanocomposite consisting of undecylenic acid modified thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) loaded with an anticancer drug, sorafenib, and surface-conjugated with heptakis(6-amino-6-deoxy)-β-cyclodextrin (HABCD) to show the impact of the surface polymeric functionalization on the physical and biological properties of the drug-loaded nanoparticles. Cytocompatibility studies showed that the UnTHCPSi-HABCD NPs were not toxic to breast cancer cells. HABCD also enhanced the suspensibility and both the colloidal and plasma stabilities of the UnTHCPSi NPs. UnTHCPSi-HABCD NPs showed a significantly increased interaction with breast cancer cells compared to bare NPs and also sustained the drug release. Furthermore, the sorafenib-loaded UnTHCPSi-HABCD NPs efficiently inhibited cell proliferation of the breast cancer cells.

  9. Alternative nuclear fuel cycle arrangements for proliferation resistance: an overview of regulatory factors

    International Nuclear Information System (INIS)

    O'Brien, J.N.

    1982-08-01

    President Carter proposed the International Fuel Cycle Evaluation to analyze various alternative fuel cycles which could minimize the risk of nuclear weapons proliferation. DOE also initiated the Non-Proliferation Alternative Systems Assessment Program. In response to GAO contentions that NRC was not sufficiently involved in these two assessments, a NRC study was initiated, with emphasis on legal and institutional factors. Objectives were to examine multinational fuel cycle facilities, potential effects on the US/IAEA agreement, development of an algorithm for ranking potential fuel cycles, and potential licensing of candidate fuel cycles. This anthology represents the products of this study which has been conducted between 1979 and 1981

  10. Sustainability.

    Science.gov (United States)

    Chang, Chein-Chi; DiGiovanni, Kimberly; Mei, Ying; Wei, Li

    2016-10-01

    This review on Sustainability covers selected 2015 publications on the focus of Sustainability. It is divided into the following sections : • Sustainable water and wastewater utilities • Sustainable water resources management • Stormwater and green infrastructure • Sustainability in wastewater treatment • Life cycle assessment (LCA) applications • Sustainability and energy in wastewater industry, • Sustainability and asset management.

  11. Implication of protein tyrosine phosphatase 1B in MCF-7 cell proliferation and resistance to 4-OH tamoxifen

    International Nuclear Information System (INIS)

    Blanquart, Christophe; Karouri, Salah-Eddine; Issad, Tarik

    2009-01-01

    The protein tyrosine phosphatase 1B (PTP1B) and the T-cell protein tyrosine phosphatase (TC-PTP) were initially thought to be mainly anti-oncogenic. However, overexpression of PTP1B and TC-PTP has been observed in human tumors, and recent studies have demonstrated that PTP1B contributes to the appearance of breast tumors by modulating ERK pathway. In the present work, we observed that decreasing the expression of TC-PTP or PTP1B in MCF-7 cells using siRNA reduced cell proliferation without affecting cell death. This reduction in proliferation was associated with decreased ERK phosphorylation. Moreover, selection of tamoxifen-resistant MCF-7 cells, by long-term culture in presence of 4-OH tamoxifen, resulted in cells that display overexpression of PTP1B and TC-PTP, and concomitant increase in ERK and STAT3 phosphorylation. siRNA experiments showed that PTP1B, but not TC-PTP, is necessary for resistance to 4-OH tamoxifen. Therefore, our work indicates that PTP1B could be a relevant therapeutic target for treatment of tamoxifen-resistant breast cancers.

  12. Proliferation Resistance and Safeguardability Assessment of a SFR Metal Fuel Manufacturing Facility (SFMF) using the INPRO Methodology

    Energy Technology Data Exchange (ETDEWEB)

    Chang, H. L.; Ko, W. I.; Park, S. H.; Kim, H. D.; Park, G. I. [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    To illustrate the proposed Prosta process, to demonstrate its usefulness, and to provide input to a revision of the INPRO manual in the area of proliferation resistance, a case study has been carried out with a conceptually designed sodium cooled fast reactor (SFR) metal fuel manufacturing facility (SFMF), representing novel technology still in the conceptual design phase. A coarse acquisition path analysis has been carried out of the SFMF to demonstrate the assessment process with identified different target materials. The case study demonstrates the usefulness of the proposed PROSA PR assessment process and the interrelationship of the PR assessment with the safeguards-by-design process, identifying potential R and D needs. The PROSA process has been applied to a conceptually designed SFMF, representing novel technology that is still in the conceptual design phase at KAERI. The case study demonstrated that the proposed PROSA process is simpler and easier to perform than the original INPRO methodology and can be applied from the early stage of design showing the relationship of PR assessment to the safeguard-by-design process. New evaluation questionnaire for UR1 is more logical and comprehensive, and provides the legal basis enabling the IAEA to achieve its safeguards objectives including the detection of undeclared nuclear materials and activities. NES information catalogue replacing UR2 was a useful modification and supports safeguardability assessment at the NES and facility level. The proposed PROSA process is also capable to identify strengths and weaknesses of a system in the area of proliferation resistance in a generally understandable form, including R and D gaps that need to be filled in order to meet the criteria for proliferation resistance of a nuclear energy system.

  13. Piperlongumine inhibits the proliferation and survival of B-cell acute lymphoblastic leukemia cell lines irrespective of glucocorticoid resistance

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seong-Su, E-mail: seong-su-han@uiowa.edu [Division of Pediatric Hematology-Oncology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Han, Sangwoo [Health and Human Physiology, University of Iowa Carver College of Medicine, Iowa City, IA (United States); Kamberos, Natalie L. [Division of Pediatric Hematology-Oncology, University of Iowa Carver College of Medicine, Iowa City, IA (United States)

    2014-09-26

    Highlights: • PL inhibits the proliferation of B-ALL cell lines irrespective of GC-resistance. • PL selectively kills B-ALL cells by increasing ROS, but not normal counterpart. • PL does not sensitize majority of B-ALL cells to DEX. • PL represses the network of constitutively activated TFs and modulates their target genes. • PL may serve as a new therapeutic molecule for GC-resistant B-ALL. - Abstract: Piperlongumine (PL), a pepper plant alkaloid from Piper longum, has anti-inflammatory and anti-cancer properties. PL selectively kills both solid and hematologic cancer cells, but not normal counterparts. Here we evaluated the effect of PL on the proliferation and survival of B-cell acute lymphoblastic leukemia (B-ALL), including glucocorticoid (GC)-resistant B-ALL. Regardless of GC-resistance, PL inhibited the proliferation of all B-ALL cell lines, but not normal B cells, in a dose- and time-dependent manner and induced apoptosis via elevation of ROS. Interestingly, PL did not sensitize most of B-ALL cell lines to dexamethasone (DEX). Only UoC-B1 exhibited a weak synergistic effect between PL and DEX. All B-ALL cell lines tested exhibited constitutive activation of multiple transcription factors (TFs), including AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6 and YY1. Treatment of the B-ALL cells with PL significantly downregulated these TFs and modulated their target genes. While activation of AURKB, BIRC5, E2F1, and MYB mRNA levels were significantly downregulated by PL, but SOX4 and XBP levels were increased by PL. Intriguingly, PL also increased the expression of p21 in B-ALL cells through a p53-independent mechanism. Given that these TFs and their target genes play critical roles in a variety of hematological malignancies, our findings provide a strong preclinical rationale for considering PL as a new therapeutic agent for the treatment of B-cell malignancies, including B-ALL and GC-resistant B-ALL.

  14. Piperlongumine inhibits the proliferation and survival of B-cell acute lymphoblastic leukemia cell lines irrespective of glucocorticoid resistance

    International Nuclear Information System (INIS)

    Han, Seong-Su; Han, Sangwoo; Kamberos, Natalie L.

    2014-01-01

    Highlights: • PL inhibits the proliferation of B-ALL cell lines irrespective of GC-resistance. • PL selectively kills B-ALL cells by increasing ROS, but not normal counterpart. • PL does not sensitize majority of B-ALL cells to DEX. • PL represses the network of constitutively activated TFs and modulates their target genes. • PL may serve as a new therapeutic molecule for GC-resistant B-ALL. - Abstract: Piperlongumine (PL), a pepper plant alkaloid from Piper longum, has anti-inflammatory and anti-cancer properties. PL selectively kills both solid and hematologic cancer cells, but not normal counterparts. Here we evaluated the effect of PL on the proliferation and survival of B-cell acute lymphoblastic leukemia (B-ALL), including glucocorticoid (GC)-resistant B-ALL. Regardless of GC-resistance, PL inhibited the proliferation of all B-ALL cell lines, but not normal B cells, in a dose- and time-dependent manner and induced apoptosis via elevation of ROS. Interestingly, PL did not sensitize most of B-ALL cell lines to dexamethasone (DEX). Only UoC-B1 exhibited a weak synergistic effect between PL and DEX. All B-ALL cell lines tested exhibited constitutive activation of multiple transcription factors (TFs), including AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6 and YY1. Treatment of the B-ALL cells with PL significantly downregulated these TFs and modulated their target genes. While activation of AURKB, BIRC5, E2F1, and MYB mRNA levels were significantly downregulated by PL, but SOX4 and XBP levels were increased by PL. Intriguingly, PL also increased the expression of p21 in B-ALL cells through a p53-independent mechanism. Given that these TFs and their target genes play critical roles in a variety of hematological malignancies, our findings provide a strong preclinical rationale for considering PL as a new therapeutic agent for the treatment of B-cell malignancies, including B-ALL and GC-resistant B-ALL

  15. EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome.

    Science.gov (United States)

    Sato, Mototaka; Nakai, Yasutomo; Nakata, Wataru; Yoshida, Takahiro; Hatano, Koji; Kawashima, Atsunari; Fujita, Kazutoshi; Uemura, Motohide; Takayama, Hitoshi; Nonomura, Norio

    2013-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC) is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC. EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined. EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA) in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni). EMMPRIN-overexpressing RCC cells were resistant to sunitinib. Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.

  16. EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome.

    Directory of Open Access Journals (Sweden)

    Mototaka Sato

    Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN has been reported to play crucial roles, including in angiogenesis, in several carcinomas. However, the correlation between EMMPRIN levels and angiogenesis expression profile has not been reported, and the role of EMMPRIN in renal cell carcinoma (RCC is unclear. In the present study, we evaluated the association of EMMPRIN with angiogenesis, its value in prognosis, and its roles in RCC.EMMPRIN expression was examined in 50 RCC patients treated with radical nephrectomy. Angiogenesis, proliferation, and invasion activity were evaluated using EMMPRIN knockdown RCC cell lines. The size of EMMPRIN-overexpressing xenografts was measured and the degree of angiogenesis was quantified. EMMPRIN expression was evaluated in RCC patients who received sunitinib therapy and in sunitinib-resistant cells. Further, the relation between EMMPRIN expression and sensitivity to sunitinib was examined.EMMPRIN score was significantly associated with clinicopathological parameters in RCC patients, as well as being significantly correlated with microvessel area (MVA in immature vessels and with prognosis. Down-regulation of EMMPRIN by siRNA led to decreased VEGF and bFGF expression, cell proliferation, and invasive potential. EMMPRIN over-expressing xenografts showed accelerated growth and MVA of immature vessels. EMMPRIN expression was significantly increased in patients who received sunitinib therapy as well as in sunitinib-resistant 786-O cells (786-suni. EMMPRIN-overexpressing RCC cells were resistant to sunitinib.Our findings indicate that high expression of EMMPRIN in RCC plays important roles in tumor progression and sunitinib resistance. Therefore, EMMPRIN could be a novel target for the treatment of RCC.

  17. From riches to rags : biofuels, media discourses and resistance to sustainable energy technologies

    NARCIS (Netherlands)

    Sengers, F.H.; Raven, R.P.J.M.; Venrooij, A.

    2010-01-01

    This study aims to open the black box of resistance to sustainable energy technologies by analyzing (shifts in) media discourse. To this end, media coverage on biofuels in the Netherlands between 2000 and 2008 is analyzed by means of combining novel quantitative approaches with practitioner

  18. From riches to rags : biofuels, media discourse and resistance to sustainable energy technologies

    NARCIS (Netherlands)

    Sengers, F.H.; Raven, R.P.J.M.; Venrooij, A.

    2010-01-01

    This study aims to open the black box of resistance to sustainable energy technologies by analyzing (shifts in) media discourse. To this end, media coverage on biofuels in the Netherlands between 2000 and 2008 is analyzed by means of combining novel quantitative approaches with practitioner

  19. From riches to rags: Biofuels, media discourses, and resistance to sustainable energy technologies

    NARCIS (Netherlands)

    R.M.A. Sengers (Rozemarijn); R.P.J.M. Raven (Rob); A.T. van Venrooij (Alex)

    2010-01-01

    textabstractThis study aims to open the black box of resistance to sustainable energy technologies by analyzing (shifts in) media discourse. To this end, media coverage on biofuels in the Netherlands between 2000 and 2008 is analyzed by means of combining novel quantitative approaches with

  20. From riches to rags: biofuels, media discourses and resistance to sustainable energy technologies

    NARCIS (Netherlands)

    Sengers, F.; Raven, R.P.J.M.; van Venrooij, A.

    2010-01-01

    This study aims to open the black box of resistance to sustainable energy technologies by analyzing (shifts in) media discourse. To this end, media coverage on biofuels in the Netherlands between 2000 and 2008 is analyzed by means of combining novel quantitative approaches with practitioner

  1. Pathway Aggregation in the Risk Assessment of Proliferation Resistance and Physical Protection (PR&PP) of Nuclear Energy Systems

    International Nuclear Information System (INIS)

    2015-01-01

    The framework for Proliferation Resistance and Physical Protection (PR & PP) evaluation is to define a set of challenges, to obtain the system responses, and to assess the outcomes. The assessment of outcomes heavily relies on pathways, defined as sequences of events or actions that could potentially be followed by a State or a group of individuals in order to achieve a proliferation objective, with the defined threats as initiating events. There may be large number of segments connecting pathway stages (e.g. acquisition, processing, and fabrication for PR) which can lead to even larger number of pathways or scenarios through possible different combinations of segment connections, each with associated probabilities contributing to the overall risk. Clustering of these scenarios in specified stage attribute intervals is important for their tractable analysis and outcome assessment. A software tool for scenario generation and clustering (OSUPR) is developed that utilizes the PRCALC code developed at the Brookhaven National Laboratory for scenario generation and the K- means, mean shift and adaptive mean shift algorithms as possible clustering schemes. The results of the study using the Example Sodium Fast Breeder as an example system show that clustering facilitates the probabilistic or deterministic analysis of scenarios to identify system vulnerabilities and communication of the major risk contributors to stakeholders. The results of the study also show that the mean shift algorithm has the most potential for assisting the analysis of the scenarios generated by PRCALC.

  2. Pathway Aggregation in the Risk Assessment of Proliferation Resistance and Physical Protection (PR&PP) of Nuclear Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Aldemir, Tunc [Ohio State Univ., Columbus, OH (United States); Denning, Richard [Ohio State Univ., Columbus, OH (United States); Catalyurek, Umit [Ohio State Univ., Columbus, OH (United States); Yilmaz, Alper [Ohio State Univ., Columbus, OH (United States); Yue, Meng [Brookhaven National Lab. (BNL), Upton, NY (United States); Cheng, Lap-Yan [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2015-01-23

    The framework for Proliferation Resistance and Physical Protection (PR & PP) evaluation is to define a set of challenges, to obtain the system responses, and to assess the outcomes. The assessment of outcomes heavily relies on pathways, defined as sequences of events or actions that could potentially be followed by a State or a group of individuals in order to achieve a proliferation objective, with the defined threats as initiating events. There may be large number of segments connecting pathway stages (e.g. acquisition, processing, and fabrication for PR) which can lead to even larger number of pathways or scenarios through possible different combinations of segment connections, each with associated probabilities contributing to the overall risk. Clustering of these scenarios in specified stage attribute intervals is important for their tractable analysis and outcome assessment. A software tool for scenario generation and clustering (OSUPR) is developed that utilizes the PRCALC code developed at the Brookhaven National Laboratory for scenario generation and the K- means, mean shift and adaptive mean shift algorithms as possible clustering schemes. The results of the study using the Example Sodium Fast Breeder as an example system show that clustering facilitates the probabilistic or deterministic analysis of scenarios to identify system vulnerabilities and communication of the major risk contributors to stakeholders. The results of the study also show that the mean shift algorithm has the most potential for assisting the analysis of the scenarios generated by PRCALC.

  3. Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1α and VEGF mRNA abundances.

    Science.gov (United States)

    Item, Flurin; Nocito, Antonio; Thöny, Sandra; Bächler, Thomas; Boutellier, Urs; Wenger, Roland H; Toigo, Marco

    2013-04-01

    We previously reported that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion (vibroX) markedly improves cycling endurance capacity, increases capillary-to-fibre ratio and skeletal muscle oxidative enzyme activity in untrained young women. These findings are intriguing, since increases in oxidative muscle phenotype and endurance capacity are typically induced by endurance but not heavy resistance exercise. Here, we tested the hypothesis that vibroX activates genes associated with mitochondrial biogenesis and angiogenesis. Eight healthy, recreationally resistance-trained young men performed either vibroX or resistance exercise (RES) in a randomised, cross-over design. Needle biopsies (M. vastus lateralis) were obtained at rest and 3 h post-exercise. Changes in relative gene expression levels were assessed by real-time quantitative PCR. After vibroX, vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator 1α mRNA abundances increased to 2- and 4.4-fold, respectively, but did not significantly change above resting values after RES. Other genes involved in mitochondrial biogenesis were not affected by either exercise modality. While vibroX increased the expression of hexokinase II, xanthine dehydrogenase, and manganese superoxide dismutase mRNA, there were no changes in these transcripts after RES. This study demonstrates that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion activates metabolic and angiogenic gene programs, which are usually activated after endurance but not resistance exercise. Thus, targeted modification of high load resistance exercise by vibration and vascular occlusion might represent a novel strategy to induce endurance-type muscle adaptations.

  4. Enhanced satellite cell proliferation with resistance training in elderly men and women

    DEFF Research Database (Denmark)

    Mackey, Abigail; Esmarck, B; Kadi, F

    2007-01-01

    In addition to the well-documented loss of muscle mass and strength associated with aging, there is evidence for the attenuating effects of aging on the number of satellite cells in human skeletal muscle. The aim of this study was to investigate the response of satellite cells in elderly men...... and women to 12 weeks of resistance training. Biopsies were collected from the m. vastus lateralis of 13 healthy elderly men and 16 healthy elderly women (mean age 76+/-SD 3 years) before and after the training period. Satellite cells were visualized by immunohistochemical staining of muscle cross.......15+/-0.06; mean+/-SD) and females (from 0.11+/-0.04 to 0.13+/-0.05). These results suggest that 12 weeks of resistance training is effective in enhancing the satellite cell pool in skeletal muscle in the elderly....

  5. Fate and proliferation of typical antibiotic resistance genes in five full-scale pharmaceutical wastewater treatment plants

    International Nuclear Information System (INIS)

    Wang, Jilu; Mao, Daqing; Mu, Quanhua; Luo, Yi

    2015-01-01

    This study investigated the characteristics of 10 subtypes of antibiotic resistance genes (ARGs) for sulfonamide, tetracycline, β-lactam and macrolide resistance and the class 1 integrase gene (intI1). In total, these genes were monitored in 24 samples across each stage of five full-scale pharmaceutical wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the final effluents ranged from (2.08 ± 0.16) × 10 3 to (3.68 ± 0.27) × 10 6 copies/mL. The absolute abundance of ARGs in effluents accounted for only 0.6%–59.8% of influents of the five PWWTPs, while the majority of the ARGs were transported to the dewatered sludge with concentrations from (9.38 ± 0.73) × 10 7 to (4.30 ± 0.81) × 10 10 copies/g dry weight (dw). The total loads of ARGs discharged through dewatered sludge was 7–308 folds higher than that in the raw influents and 16–638 folds higher than that in the final effluents. The proliferation of ARGs mainly occurs in the biological treatment processes, such as conventional activated sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR), implying that significant replication of certain subtypes of ARGs may be attributable to microbial growth. High concentrations of antibiotic residues (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected wastewater treatment systems and they still remain high residues in the effluents. Partial correlation analysis showed significant correlations between the antibiotic concentrations and the associated relative abundance of ARG subtypes in the effluent. Although correlation does not prove causation, this study demonstrates that in addition to bacterial growth, the high antibiotic residues within the pharmaceutical WWTPs may influence the proliferation and fate of the associated ARG subtypes. - Highlights: • The ARGs in final discharges were 7–308 times higher than

  6. Fate and proliferation of typical antibiotic resistance genes in five full-scale pharmaceutical wastewater treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jilu [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Mao, Daqing, E-mail: mao@tju.edu.cn [School of Environmental Science and Engineering, Tianjin University, Tianjin 300072 (China); Mu, Quanhua [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Luo, Yi, E-mail: luoy@nankai.edu.cn [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China)

    2015-09-01

    This study investigated the characteristics of 10 subtypes of antibiotic resistance genes (ARGs) for sulfonamide, tetracycline, β-lactam and macrolide resistance and the class 1 integrase gene (intI1). In total, these genes were monitored in 24 samples across each stage of five full-scale pharmaceutical wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the final effluents ranged from (2.08 ± 0.16) × 10{sup 3} to (3.68 ± 0.27) × 10{sup 6} copies/mL. The absolute abundance of ARGs in effluents accounted for only 0.6%–59.8% of influents of the five PWWTPs, while the majority of the ARGs were transported to the dewatered sludge with concentrations from (9.38 ± 0.73) × 10{sup 7} to (4.30 ± 0.81) × 10{sup 10} copies/g dry weight (dw). The total loads of ARGs discharged through dewatered sludge was 7–308 folds higher than that in the raw influents and 16–638 folds higher than that in the final effluents. The proliferation of ARGs mainly occurs in the biological treatment processes, such as conventional activated sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR), implying that significant replication of certain subtypes of ARGs may be attributable to microbial growth. High concentrations of antibiotic residues (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected wastewater treatment systems and they still remain high residues in the effluents. Partial correlation analysis showed significant correlations between the antibiotic concentrations and the associated relative abundance of ARG subtypes in the effluent. Although correlation does not prove causation, this study demonstrates that in addition to bacterial growth, the high antibiotic residues within the pharmaceutical WWTPs may influence the proliferation and fate of the associated ARG subtypes. - Highlights: • The ARGs in final discharges were 7

  7. Variations of uranium and plutonium coprocessing as proliferation-resistant alternatives to the classical purex process

    International Nuclear Information System (INIS)

    Buckham, J.A.; Sumner, W.B.

    1979-08-01

    Evaluation of these alternatives for processing LWR fuel has led to the following conclusions: (1) None of the alternaives provide a pure, technical solution which completely eliminates the potential for proliferation of nuclear weapons by utilizing plutonium from the light water reactors. (2) The heat spike alternative appears feasible and provides the most effective method of rendering the LWR plutonim unattractive for weapons use. (3) The low-DF process alternate would require demonstration to: (a) determine the reliability of the in-cell recycle streams which are used to prevent reversion of the process for purification of plutonium, and (b) verify the fission product decontamination factors. (4) The alternates evaluated have no significant impacts on the design of waste treatment facilities, although the required capacities of high-level solid waste processing and high-level liquid waste storage can be significantly altered. (5) The impact of these alternate processes on fuel fabrication and other aspects of the fuel cycle requires additional evaluation

  8. Impact resistance of sustainable construction material using light weight oil palm shells reinforced geogrid concrete slab

    International Nuclear Information System (INIS)

    Muda, Z C; Usman, F; Beddu, S; Alam, M A; Mustapha, K N; Birima, A H; Sidek, L M; Rashid, M A; Malik, G; Zarroq, O S

    2013-01-01

    This paper investigate the performance of lightweight oil palm shells (OPS) concrete slab with geogrid reinforcement of 300mm × 300mm size with 20mm, 30mm and 40 mm thick casted with different geogrid orientation and boundary conditions subjected to low impact projectile test. A self-fabricated drop-weight impact test rig with a steel ball weight of 1.2 kg drop at 1 m height has been used in this research work. The main variables for the study is to find the relationship of the impact resistance the slab thickness, boundary conditions and geogrid reinforcement orientation. Test results indicate that the used of the geogrid reinforcement increased the impact resistance under service (first) limit crack up to 5.9 times and at ultimate limit crack up to 20.1 times against the control sample (without geogrid). A good linear relationship has been established between first and ultimate crack resistance against the slab thickness. The orientation of the geogrid has minor significant to the crack resistance of the OPS concrete slab. OPS geogrid reinforced slab has a good crack resistance properties that can be utilized as a sustainable impact resistance construction materials.

  9. Proliferation resistance of the fuel cycle for the Integral Fast Reactor

    International Nuclear Information System (INIS)

    Burris, L.

    1993-01-01

    Argonne National Laboratory has developed an electrorefining pyrochemical process for recovery and recycle of metal fuel discharged from the Integral Fast Reactor (FR). This inherently low decontamination process has an overall decontamination factor of only about 100 for the plutonium metal product. As a result, all of the fuel cycle operations must be conducted in heavily shielded cells containing a high-purity argon atmosphere. The FR fuel cycle possesses high resistance to clandestine diversion or overt, state- supported removal of plutonium for nuclear weapons production because of two main factors: the highly radioactive product, which is also contaminated with heat- and neutron-producing isotopes of plutonium and other actinide elements, and the difficulty of removing material from the FR facility through the limited number of cell transfer locks without detection

  10. GP88 (PC-Cell Derived Growth Factor, progranulin stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

    Directory of Open Access Journals (Sweden)

    Sabnis Gauri

    2011-06-01

    Full Text Available Abstract Background Aromatase inhibitors (AI that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+ breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88, also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer.

  11. The Proliferation Resistance of a Nuclear Fuel Cycle Using Fuel Recovered from the Electrolytic Reduction of Pressurized Water Reactor Spent Fuel

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jung Min; Cochran, Thomas; Mckinzie, Matthew [NRDC, Washington, (United States)

    2016-05-15

    At some points in the fuel cycle, a level of intrinsic or technical proliferation-resistance can be provided by radiation barriers that surround weapons-usable materials. In this report we examine some aspects of intrinsic proliferation resistance of a fuel cycle for a fast neutron reactor that uses fuel recovered from the electrolytic reduction process of pressurized water reactor spent fuel, followed by a melt-refining process. This fuel cycle, proposed by a nuclear engineer at the Korea Advanced Institute of Science and Technology (KAIST), is being examined with respect to its potential merits of higher fuel utilization, lower production of radioactive byproducts, and better economics relative to a pyroprocesing-based fuel cycle. With respect to intrinsic proliferation resistance, however, we show that since europium is separated out during the electrolytic reduction process, this fuel cycle has little merit beyond that of a pyroprocessing-based fuel cycle because of the lower radiation barrier of its recovered materials containing weapons-usable actinides. Unless europium is not separated following voloxidation, the proposed KAIST fuel cycle is not intrinsically proliferation resistant and in this regard does not represent a significant improvement over pyroprocessing. We suggest further modification of the proposed KAIST fuel cycle, namely, omitting electrolytic reduction and melt reduction, and producing the fast reactor fuel directly following voloxidation.

  12. Effect of copper nanoparticles administered in ovo on the activity of proliferating cells and on the resistance of femoral bones in broiler chickens

    DEFF Research Database (Denmark)

    Mroczek-Sosnowska, Natalia; Lukasiewicz, Monika; Adamek, Dobrochna

    2017-01-01

    The objective of this study was to evaluate bone resistance after in ovo administration of copper nanoparticles (NanoCu) and to determine the number of cells positive for proliferating cell nuclear antigen (PCNA) in the femoral bones of broiler chickens (n = 12 per group). The study demonstrated...... that femoral bones from the NanoCu group were characterised by a higher weight and volume and by significantly greater resistance to fractures compared to the Control group. NanoCu promoted the proliferation of PCNA-positive cells in the long bones of chickens. A significantly higher number of PCNA......-positive cells in the bones of birds in the NanoCu group compared with the Control group (137 and 122, respectively) indicate a stimulatory effect during embryogenesis. Considering the improvement in bone resistance to fractures and the effect of NanoCu on the number of PCNA-positive cells in femoral bones, Nano...

  13. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Hee-Jin [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of); Kim, Gwangil [Department of Pathology, CHA Bundang Medical Center, CHA University, Seoul (Korea, Republic of); Park, Kyung-Soon, E-mail: kspark@cha.ac.kr [Department of Biomedical Science, College of Life Science, CHA University, Seoul (Korea, Republic of)

    2013-08-09

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway.

  14. Ell3 stimulates proliferation, drug resistance, and cancer stem cell properties of breast cancer cells via a MEK/ERK-dependent signaling pathway

    International Nuclear Information System (INIS)

    Ahn, Hee-Jin; Kim, Gwangil; Park, Kyung-Soon

    2013-01-01

    Highlights: •Ell3 enhances proliferation and drug resistance of breast cancer cell lines. •Ell3 is related to the cancer stem cell characteristics of breast cancer cell lines. •Ell3 enhances oncogenicity of breast cancer through the ERK1/2 signaling pathway. -- Abstract: Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven−nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53 and regulates cell proliferation and survival. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis via the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. MCF-7 cell lines overexpressing Ell3 were used to examine cell proliferation and cancer stem cell properties. Ectopic expression of Ell3 in breast cancer cell lines induces proliferation and 5-FU resistance. In addition, Ell3 expression increases the cancer stem cell population, which is characterized by CD44 (+) or ALDH1 (+) cells. Mammosphere-forming potential and migration ability were also increased upon Ell3 expression in breast cancer cell lines. Through biochemical and molecular biological analyses, we showed that Ell3 regulates proliferation, cancer stem cell properties and drug resistance in breast cancer cell lines partly through the MEK−extracellular signal-regulated kinase signaling pathway. Murine xenograft experiments showed that Ell3 expression promotes tumorigenesis in vivo. These results suggest that Ell3 may play a critical role in promoting oncogenesis in breast cancer by regulating cell proliferation and cancer stem cell properties via the ERK1/2 signaling pathway

  15. Program of enhancing the Korea-USA cooperation research for the development of proliferation resistant fuel cycle technology

    International Nuclear Information System (INIS)

    Yang, Myung Seung; Ahn, D. H.; Ko, W. I.

    2007-03-01

    The objective of the Program is to develop the fuel cycle technology of GEN-IV SFR (Sodium Fast Reactor) system through the Korea-USA cooperation research in order to improve the efficiency of the technology development and to increase the transparency of the research. Since the pyroprocessing research by using actual spent nuclear fuel can not be performed in Korea at present, the active demonstration research will be performed by using the USA national research facilities under the Korea-USA cooperation. Moreover, the development of safeguards technology and the methodology for the evaluation of the proliferation resistance will also be performed under the cooperation. The current cooperation national laboratories of the safeguards and pyroprocessing technology development are LANL (Los Alamos National Lab.) and INL (Idaho National Lab.), respectively. Practical research experience and technical data for the pyroprocessing technology can be achieved through the demonstration of the inactive research results, which was performed in Korea, by using actual spent nuclear fuel. The scope of the cooperation study encompass the electrolytic reduction of oxide spent fuel, electrorefining, liquid cadmium cathode process, TRU fuel fabrication, fuel performance evaluation and related safeguards technology development

  16. From riches to rags: Biofuels, media discourses, and resistance to sustainable energy technologies

    Energy Technology Data Exchange (ETDEWEB)

    Sengers, F. [Eindhoven University of Technology, School of Innovation Sciences, PO Box 513, 5600 MB, Eindhoven (Netherlands); Raven, R.P.J.M., E-mail: r.p.j.m.raven@tue.n [Eindhoven University of Technology, School of Innovation Sciences, PO Box 513, 5600 MB, Eindhoven (Netherlands); Van Venrooij, A. [Erasmus University, Department for the Study of Arts and Culture, PO Box 1738, 3000 DR Rotterdam (Netherlands)

    2010-09-15

    This study aims to open the black box of resistance to sustainable energy technologies by analyzing (shifts in) media discourse. To this end, media coverage on biofuels in the Netherlands between 2000 and 2008 is analyzed by means of combining novel quantitative approaches with practitioner interviews. The quantitative analyses reveal the dynamics in the content of media discourse, but also its underlying structure in the form of two axes, each representing opposite socio-cognitive frames: 'techno-economic vs. social-ecological' and 'regional vs. global'. In-depth interviews with key practitioners in the Dutch biofuels field support these finding and provide additional insights with regard to (a) perceived shifts in media coverage; (b) cognitive pluralism; (c) the politics involved; and (d) resistance in practice.

  17. From riches to rags: Biofuels, media discourses, and resistance to sustainable energy technologies

    International Nuclear Information System (INIS)

    Sengers, F.; Raven, R.P.J.M.; Van Venrooij, A.

    2010-01-01

    This study aims to open the black box of resistance to sustainable energy technologies by analyzing (shifts in) media discourse. To this end, media coverage on biofuels in the Netherlands between 2000 and 2008 is analyzed by means of combining novel quantitative approaches with practitioner interviews. The quantitative analyses reveal the dynamics in the content of media discourse, but also its underlying structure in the form of two axes, each representing opposite socio-cognitive frames: 'techno-economic vs. social-ecological' and 'regional vs. global'. In-depth interviews with key practitioners in the Dutch biofuels field support these finding and provide additional insights with regard to (a) perceived shifts in media coverage; (b) cognitive pluralism; (c) the politics involved; and (d) resistance in practice.

  18. The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin.

    Science.gov (United States)

    Cazzaniga, Alessandra; Moscheni, Claudia; Trapani, Valentina; Wolf, Federica I; Farruggia, Giovanna; Sargenti, Azzurra; Iotti, Stefano; Maier, Jeanette A M; Castiglioni, Sara

    2017-01-17

    The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion channel kinase TRPM7. We demonstrate that the different amounts of TRPM7 and MagT1 account for the different proliferation rate of sensitive and resistant colon carcinoma cells. It remains to be verified whether they are also involved in the control of other "staminal" traits.

  19. [Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

    Science.gov (United States)

    Lin, Juan-Na; Kuang, Qiao-Ting; Ye, Kai-He; Ye, Chun-Ling; Huang, Yi; Zhang, Xiao-Qi; Ye, Wen-Cai

    2013-08-01

    To investigate the influences of triterpenoid from Psidium guajava Leaves (ursolic acid) on the proliferation, differentiation of 3T3-L1 preadipocyte, and its possible mechanism treat for insulin resistance. 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h, the cell viability was tested by MTT assay. Induced for 6 days, the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARgamma and PTP1B in insulin resistant adipocyte were measured by Western Blotting. Compared with medium control group, 30, 100 micromol/L ursolic acid could increase its proliferation and differentiation significantly (P 0.05). Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte, enhance cellular glucose uptake, inhibit the production of FFA, promote the secretion of adiponectin insulin resistant adipocyte, its mechanism may be related to upregulating the expression of PPARgamma protein.

  20. Revision of Sustainable Criteria of Concrete Walls for Earthquake-Resistant Housing

    Directory of Open Access Journals (Sweden)

    Alcocer S.M.

    2012-10-01

    Full Text Available The seismic performance of low-rise housing has been noticeably inadequate during the most recent earthquakes occurred in Latin American countries. Moreover, the literature review revealed that some traditional techniques do not contribute to building sustainable housing. In the last decade, construction of concrete walls housing has become a preferred choice because of the speed of construction and availability of materials in most of these countries. Aimed at improving seismic design methods for this type of construction, an extensive analytical and experimental program was carried out. The experimental program included quasi-static and shaking-table tests of 47 walls with different height-to-length ratios and walls with openings. Variables studied were type of concrete, web steel ratio and type of web reinforcement. The paper presents and discusses the main results of the research program and evaluates the technical and environmental feasibility for using concrete walls for sustainable and earthquake-resistant housing. Performance of concrete walls housing is assessed in terms of key environmental and earthquake-resistant requirements. It was found that concrete wall housing is not only safe under earthquakes and easily adaptable to climate, but also it stimulates environmental conservation and promotes reducing the costs of construction, operation and maintenance.

  1. Resilience versus Resistance: Affectively Modulating Contemporary Diagrams of Social Resilience, Social Sustainability, and Social Innovation

    Directory of Open Access Journals (Sweden)

    Petra Hroch

    2013-11-01

    Full Text Available This article critically interrogates the twin notions of social sustainability and activities grouped under the term social innovation in order to argue that sustainability and innovation are schizoid modes of representing what Deleuze calls “the cliché” (the authority of the same as “the new” (difference that short-circuit any real possibility of social transformation. I argue that the kinds of solutions presented by social innovation to the problems of social sustainability in the context of a neoliberal governmentality are sustainable only in the sense that they are a model for a more collective mode of existence in an individualized realm that reciprocally supports a realm in which collective responsibility is individualized. In other words, this neo-liberal diagram catches and captures creative energies in service to the status quo. To illustrate these ideas I turn to Dutch filmmaker Bregtje van der Haak’s 2010 documentary, California Dreaming, in which she compares the popular response to the 2008 financial crisis by focusing on several families across the transatlantic transcontinental divide. She interviews Europeans who blame the state as the source of the economic problem, and thus expect the state to fix it. And she interviews Americans who, reflecting on the “American dream,” reveal their faith in meritocracy, blame themselves, and thus look to their own families and communities for solutions. Their respective stories tell us how different neo-liberal diagrams structure and modulate subjectivity and its relation to the social, as well as the emerging ways in which this relation is being framed. If, as Deleuze writes, “there is no diagram that does not also include, besides the points which it connects up, certain relatively free points, points of creativity, change and resistance,” how can analysis of these shifty subjective-social structures point us to points of resistance" (Foucault? And why is it crucial that

  2. User requirements for innovative nuclear reactors and fuel cycle technologies in the area of economics, environment, safety, waste management, proliferation resistance and cross cutting issues, and methodology for innovative technologies assessment

    International Nuclear Information System (INIS)

    Kupitz, Juergen; Depisch, Frank; Allan, Colin

    2003-01-01

    The IAEA General Conference in 2000 has invited ''all interested Member States to combine their efforts under the aegis of the Agency in considering the issues of the nuclear fuel cycle, in particular by examining innovative and proliferation-resistant nuclear technology''. In response to this invitation, the IAEA initiated an ''International Project on Innovative Nuclear Reactors and Fuel Cycles'', INPRO. The overall objectives of INPRO is to help to ensure that nuclear energy is available to contribute in fulfilling in a sustainable manner energy needs in the 21st century, and to bring together all interested Member States, both technology holders and technology users, to consider jointly the international and national actions required to achieve desired innovations in nuclear reactors and fuel cycles that use sound and economically competitive technology. Phase-I of INPRO was initiated in May 2001. During Phase-I, work was subdivided in two sub phase: Phase 1A (finished in June 2003) and Phase 1B (started in June 2003). Phase 1A dealt with the definition of Basic Principles, User Requirements and Criteria, and the development of a methodology for the evaluation of innovative nuclear technologies. In Phase 1A, task groups for several areas were established: (a) Prospects and Potentials of Nuclear Power, (b) Economics; (c) Sustainability and Environment, (d) Safety of Nuclear Installations, (e) Waste Management, (f) Proliferation Resistance, (g) Crosscutting issues and (h) for the Methodology for Assessment. In Phase-IB evaluations of innovative nuclear energy technologies will be performed by Member States against the INPRO Basic Principles, User Requirements and Criteria. This paper summarizes the results achieved in the Phase 1A of INPRO and is a cooperative effort of the INPRO team, consisting of all INPRO cost free experts and task managers. (author)

  3. Partial resistance to stripe rust and its effect on sustainability of wheat yield

    International Nuclear Information System (INIS)

    Qamar, M.; Din, R.U.; Gardazi, D.A.

    2014-01-01

    Stripe rust (Puccinia striiformis Westend. f. sp. tritici) poses a serious threat to wheat production in cooler areas of Pakistan. The 70% area of wheat in Pakistan is prone to stripe rust disease. It can cause 10-17% yield losses if susceptible cultivars are planted under favorable conditions. Level of partial plant resistance in bread wheat and its impact on sustainable wheat production was studied at the National Agricultural Research Centre, Islamabad under natural conditions in the field. Eleven Pakistani commercial wheat cultivars/advance lines including check (Inqalab 91) were assessed for the level of partial resistance against stripe rust using Area Under the Disease Progress Curve (AUDPC), disease severity (DS) and epidemic growth rate in comparison with wheat cultivar, Inqalab 91. During 2007 cropping season, natural epidemic was developed and relative AUDPC was recorded from 0 to 100% whereas the 2008 cropping season was dry and no stripe rust appeared. Two advanced lines (NR 268 and NR 285) showed the infection type (IT) less than 7 (incompatible reaction) to the mixture of prevailing stripe rust inoculums. Very low level of DS and AUDPC were recorded in the remaining cultivars/lines indicating a high level of partial resistance to stripe rust compared to the susceptible check cultivar, Inqalab 91. Among eight cultivars/lines that showed compatible type of reaction (IT greater then equal to 7), one was resistant (relative AUDPC = 20% of Inqalab 91) and six showed very high resistance levels (relative AUDPC greater then equal to 5%). Maximum level of resistance (relative AUDPC = 0.1%) was observed in advanced line, NR 271. The wheat cultivars/lines that showed a slow disease development (low DS and AUDPC), could be considered as -1 partially resistant for stripe rust infection. The yield (2178 kg ha) of susceptible check cultivar Inqalab-91 during 2007 was reduced to 45% as -1 compared to its yield (3945 kg ha) in epidemic free year (2008). Thus the use

  4. IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model

    International Nuclear Information System (INIS)

    Jia, Yanhan; Zhang, Yan; Qiao, Chunxia; Liu, Guijun; Zhao, Qing; Zhou, Tingting; Chen, Guojiang; Li, Yali; Feng, Jiannan; Li, Yan; Zhang, Qiuping; Peng, Hui

    2013-01-01

    Highlights: •We established trastuzumab-resistant cell line SKOV3/T. •SKOV3/T enhances proliferation and in vivo carcinogenesis. •IGF-1R and HER3 genes were up-regulated in SKOV3/T based on microarray analysis. •Targeting IGF-1R and/or HER3 inhibited the proliferation of SKOV3/T. •Therapies targeting IGF-1R and HER3 might be effective in ovarian cancer. -- Abstract: Trastuzumab (Herceptin®) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer

  5. IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Yanhan [Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China); Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhang, Yan [Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Qiao, Chunxia; Liu, Guijun [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhao, Qing [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Zhou, Tingting; Chen, Guojiang [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Li, Yali [Department of Gynaecology and Obstetrics, PLA General Hospital, Beijing 100853 (China); Feng, Jiannan; Li, Yan [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Zhang, Qiuping, E-mail: qpzhang@whu.edu.cn [Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430071 (China); Peng, Hui, E-mail: p_h2002@hotmail.com [Department of Immunology, Institute of Basic Medical Sciences, Beijing 100850 (China); Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Beijing 100850 (China)

    2013-07-12

    Highlights: •We established trastuzumab-resistant cell line SKOV3/T. •SKOV3/T enhances proliferation and in vivo carcinogenesis. •IGF-1R and HER3 genes were up-regulated in SKOV3/T based on microarray analysis. •Targeting IGF-1R and/or HER3 inhibited the proliferation of SKOV3/T. •Therapies targeting IGF-1R and HER3 might be effective in ovarian cancer. -- Abstract: Trastuzumab (Herceptin®) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer.

  6. Y-box-binding protein-1 (YB-1) promotes cell proliferation, adhesion and drug resistance in diffuse large B-cell lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Miao, Xiaobing; Wu, Yaxun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Wang, Yuchan [Department of Pathogen, Medical College, Nantong University, Nantong 226001, Jiangsu (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Zhu, Xinghua; Yin, Haibing [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Yunhua [Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu (China); Li, Chunsun; Liu, Yushan; Lu, Xiaoyun; Chen, Yali; Shen, Rong [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); Xu, Xiaohong, E-mail: xuxiaohongnantong@126.com [Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong 226361, Jiangsu (China)

    2016-08-15

    YB-1 is a multifunctional protein, which has been shown to correlate with resistance to treatment of various tumor types. This study investigated the expression and biologic function of YB-1 in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical analysis showed that the expression statuses of YB-1 and pYB-1{sup S102} were reversely correlated with the clinical outcomes of DLBCL patients. In addition, we found that YB-1 could promote the proliferation of DLBCL cells by accelerating the G1/S transition. Ectopic expression of YB-1 could markedly increase the expression of cell cycle regulators cyclin D1 and cyclin E. Furthermore, we found that adhesion of DLBCL cells to fibronectin (FN) could increase YB-1 phosphorylation at Ser102 and pYB-1{sup S102} nuclear translocation. In addition, overexpression of YB-1 could increase the adhesion of DLBCL cells to FN. Intriguingly, we found that YB-1 overexpression could confer drug resistance through cell-adhesion dependent and independent mechanisms in DLBCL. Silencing of YB-1 could sensitize DLBCL cells to mitoxantrone and overcome cell adhesion-mediated drug resistance (CAM-DR) phenotype in an AKT-dependent manner. - Highlights: • The expression statuses of YB-1 and pYB-1{sup S102} are reversely correlated with outcomes of DLBCL patients. • YB-1 promotes cell proliferation by accelerating G1/S transition in DLBCL. • YB-1 confers drug resistance to mitoxantrone in DLBCL.

  7. Guidance for the application of an assessment methodology for innovative nuclear energy systems. INPRO manual - Proliferation resistance. Vol. 5 of the final report of phase 1 of the International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO)

    International Nuclear Information System (INIS)

    2008-11-01

    The International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) was initiated in the year 2000, based on a resolution of the IAEA General Conference (GC(44)/RES/21). The main objectives of INPRO are (1) to help to ensure that nuclear energy is available to contribute in fulfilling energy needs in the 21st century in a sustainable manner, (2) to bring together both technology holders and technology users to consider jointly the international and national actions required to achieve desired innovations in nuclear reactors and fuel cycles; and (3) to create a forum to involve all relevant stakeholders that will have an impact on, draw from, and complement the activities of existing institutions, as well as ongoing initiatives at the national and international level. The INPRO manual is comprised of an overview volume (No. 1), and eight additional volumes covering the areas of economics (Volume 2), infrastructure (Volume 3), waste management (Volume 4), proliferation resistance (laid out in this report) (Volume 5), physical protection (Volume 6), environment (Volume 7), safety of nuclear reactors (Volume 8), and safety of nuclear fuel cycle facilities (Volume 9). This volume of the INPRO manual is based on the results of an INPRO study on proliferation resistance of the DUPIC fuel cycle performed by the Republic of Korea during 2005 and 2006, recommendations from IAEA consultancy meetings, and on a special service agreement with G. Pshakin (Russian Federation). The INPRO Manual starts with an introduction in Chapter 1. In Chapter 2, the necessary information is described to perform an INPRO assessment in the area of proliferation resistance. Explanatory notes on the INPRO basic principles (BP) and user requirements (UR) in the area of proliferation resistance, are reproduced in Chapter 3 to provide context for the assessor; additionally, background of each criterion (CR) and a corresponding procedure is described how to perform an INPRO assessment. The

  8. Fissile material proliferation risk

    International Nuclear Information System (INIS)

    Dreicer, J.S.; Rutherford, D.A.

    1996-01-01

    The proliferation risk of a facility depends on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. To effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of nuclear related sites and facilities in different countries and still ensure a global decrease in proliferation risk for fissile material (plutonium and highly enriched uranium)

  9. Safety assessment for a potential SNF repository and its implication to the proliferation resistance nuclear fuel cycle

    International Nuclear Information System (INIS)

    Hwang, Y.; Jeong, M.S.; Seo, C.S.

    2007-01-01

    KAERI is developing the pyro-process technology to minimize the burden on permanent disposal of spent nuclear fuel. In addition, KAERI has developed the Korean Reference System for potential spent nuclear fuel disposal since 1997. The deep geologic disposal system is composed of a multi-barrier system in a crystalline rock to dispose of 36,000 MT of spent nuclear fuel (SNF) from a CANDU and a PWR. Quite recently, introduction of advanced nuclear fuel cycles such as pyro-processing is a big issue to solve the everlasting disposal problem and to assure the sustainable supply of fuel for reactors. To compare the effect of direct disposal of SNF with that of the high level waste disposal for waste generated from the advanced nuclear fuel cycles, the total system performance assessment for two different schemes is developed; one for direct disposal of SNF and the other for the introduction of the pyro-processing and direct disposal CANDU spent nuclear fuel. The safety indicators to assess the environmental friendliness of the disposal option are annual individual doses, toxicities and risks. Even though many scientists use the toxicity to understand the environmental friendliness of the disposal, scientifically the annual individual doses or risks are meaningful indicators for it. The major mechanisms to determine the doses and risks for direct disposal are as follows: (1) Dissolution mechanisms of uranium dioxides which control the dissolution of most nuclides such as TRU's and most parts of fission products. (2) Instant release fraction of highly soluble nuclides such as I-129, C-135, Tc-99, and others. (3) Retardation and dilution effect of natural and engineered barriers. (4) Dilution effect in the biosphere. The dominant nuclide is I-129 which follows both congruent and instantaneous release modes. Since its long half life associated with the instantaneous release I-129 is dominant well beyond one million. The impact of the TRU's is negligible until the significant

  10. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Pinilla, Mabel G. [Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C. [Department of Physiopathology, School of Biological Sciences, University of Concepcion, Concepcion (Chile); McNerney, Eileen M. [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Onate, Sergio A., E-mail: sergio.onate@udec.cl [Molecular Endocrinology and Oncology Laboratory, University of Concepcion, Concepcion (Chile); Department of Medical Specialties, School of Medicine, University of Concepcion, Concepcion (Chile); Department of Urology, State University of New York at Buffalo, NY (United States)

    2015-11-27

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  11. Bone stroma-derived cells change coregulators recruitment to androgen receptor and decrease cell proliferation in androgen-sensitive and castration-resistant prostate cancer cells

    International Nuclear Information System (INIS)

    Villagran, Marcelo A.; Gutierrez-Castro, Francisco A.; Pantoja, Diego F.; Alarcon, Jose C.; Fariña, Macarena A.; Amigo, Romina F.; Muñoz-Godoy, Natalia A.; Pinilla, Mabel G.; Peña, Eduardo A.; Gonzalez-Chavarria, Ivan; Toledo, Jorge R.; Rivas, Coralia I.; Vera, Juan C.; McNerney, Eileen M.; Onate, Sergio A.

    2015-01-01

    Prostate cancer (CaP) bone metastasis is an early event that remains inactive until later-stage progression. Reduced levels of circulating androgens, due to andropause or androgen deprivation therapies, alter androgen receptor (AR) coactivator expression. Coactivators shift the balance towards enhanced AR-mediated gene transcription that promotes progression to androgen-resistance. Disruptions in coregulators may represent a molecular switch that reactivates latent bone metastasis. Changes in AR-mediated transcription in androgen-sensitive LNCaP and androgen-resistant C4-2 cells were analyzed for AR coregulator recruitment in co-culture with Saos-2 and THP-1. The Saos-2 cell line derived from human osteosarcoma and THP-1 cell line representing human monocytes were used to display osteoblast and osteoclast activity. Increased AR activity in androgen-resistant C4-2 was due to increased AR expression and SRC1/TIF2 recruitment and decreased SMRT/NCoR expression. AR activity in both cell types was decreased over 90% when co-cultured with Saos-2 or THP-1 due to dissociation of AR from the SRC1/TIF2 and SMRT/NCoR coregulators complex, in a ligand-dependent and cell-type specific manner. In the absence of androgens, Saos-2 decreased while THP-1 increased proliferation of LNCaP cells. In contrast, both Saos-2 and THP-1 decreased proliferation of C4-2 in absence and presence of androgens. Global changes in gene expression from both CaP cell lines identified potential cell cycle and androgen regulated genes as mechanisms for changes in cell proliferation and AR-mediated transactivation in the context of bone marrow stroma cells. - Highlights: • Decreased corepressor expression change AR in androgen-resistance prostate cancer. • Bone stroma-derived cells change AR coregulator recruitment in prostate cancer. • Bone stroma cells change cell proliferation in androgen-resistant cancer cells. • Global gene expression in CaP cells is modified by bone stroma cells in co

  12. Sustained transmission of high-level azithromycin-resistant Neisseria gonorrhoeae in England: an observational study.

    Science.gov (United States)

    Fifer, Helen; Cole, Michelle; Hughes, Gwenda; Padfield, Simon; Smolarchuk, Christa; Woodford, Neil; Wensley, Adrian; Mustafa, Nazim; Schaefer, Ulf; Myers, Richard; Templeton, Kate; Shepherd, Jill; Underwood, Anthony

    2018-05-01

    Between Nov 3, 2014, and Feb 24, 2017, 70 cases of high-level azithromycin-resistant (HL-AziR; minimum inhibitory concentration [MIC] ≥256 mg/L) Neisseria gonorrhoeae were reported from across England. Whole-genome sequencing was done to investigate this outbreak to determine whether the ongoing outbreak represented clonal spread of an HL-AziR N gonorrhoeae strain identified in Leeds. We also wanted to elucidate the molecular mechanisms of azithromycin resistance in N gonorrhoeae in the UK. In this observational study, whole-genome sequencing was done on the HL-AziR N gonorrhoeae isolates from England. As comparators, 110 isolates from the UK and Ireland with a range of azithromycin MICs were also sequenced, including eight isolates from Scotland with azithromycin MICs ranging from 0·12 mg/L to 1·00 mg/L that were N gonorrhoeae multi-antigen sequence type 9768 (ST9768), which was the sequence type initially responsible for the outbreak. The presence of mutations or genes associated with azithromycin resistance was also investigated. 37 of the 60 HL-AziR isolates from England belonged to ST9768, and were genetically similar (mean 4·3 single-nucleotide polymorphisms). A 2059A→G mutation was detected in three or all four alleles of the 23S rRNA gene. Five susceptible ST9768 isolates had one mutated 23S rRNA allele and one low-level resistant ST9768 isolate had two mutated alleles. Sustained transmission of a successful HL-AziR clone was seen across England. Mutation 2059A→G was found in isolates with lower azithromycin MICs. Azithromycin exposure might have provided the selection pressure for one or two mutated copies of the 23S rRNA gene to recombine with wild-type copies, leading to three or four mutated copies and the HL-AziR phenotype. HL-AziR could emerge in isolates with low azithromycin MICs and eliminate the effectiveness of azithromycin as part of dual therapy for the treatment of gonorrhoea. Public Health England. Copyright © 2018 Elsevier Ltd. All

  13. LncRNA UCA1 promotes proliferation and cisplatin resistance of oral squamous cell carcinoma by sunppressing miR-184 expression.

    Science.gov (United States)

    Fang, Zheng; Zhao, Junfang; Xie, Weihong; Sun, Qiang; Wang, Haibin; Qiao, Bin

    2017-12-01

    Chemotherapy resistance has become the main obstacle for the effective treatment of human cancers. Long non-coding RNA urothelial cancer associated 1 (UCA1) is generally regarded as an oncogene in some cancers. However, the function and molecular mechanism of UCA1 implicated in cisplatin (CDDP) chemoresistance of oral squamous cell carcinoma (OSCC) is still not fully established. UCA1 expression in tumor tissues and cells was tested by qRT-PCR. MTT, flow cytometry and caspase-3 activity analysis were explored to evaluate the CDDP sensitivity in OSCC cells. Western blot analysis was used to measure BCL2, Bax and SF1 protein expression. Luciferase reporter assay was conducted to investigate the molecular relationship between UCA1, miR-184, and SF1. Nude mice model was used to confirm the functional role of UCA1 in CDDP resistance in vivo. UCA1 expression was upregulated in OSCC tissues, cell lines, and CDDP resistant OSCC cells. Function analysis revealed that UCA1 facilitated proliferation, enhanced CDDP chemoresistance, and suppressed apoptosis in OSCC cells. Mechanisms investigation indicated that UCA1 could interact with miR-184 to repress its expression. Rescue experiments suggested that downregulation of miR-184 partly reversed the tumor suppression effect and CDDP chemosensitivity of UCA1 knockdown in CDDP-resistant OSCC cells. Moreover, UCA1 could perform as a miR-184 sponge to modulate SF1 expression. The OSCC nude mice model experiments demonstrated that depletion of UCA1 further boosted CDDP-mediated repression effect on tumor growth. UCA1 accelerated proliferation, increased CDDP chemoresistance and restrained apoptosis partly through modulating SF1 via sponging miR-184 in OSCC cells, suggesting that targeting UCA1 may be a potential therapeutic strategy for OSCC patients. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  14. Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

    2010-01-01

    CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

  15. Options for small and medium sized reactors (SMRs) to overcome loss of economies of scale and incorporate increased proliferation resistance and energy security

    International Nuclear Information System (INIS)

    Kuznetsov, Vladimir

    2008-01-01

    The designers of innovative small and medium sized reactors pursue new design and deployment strategies making use of certain advantages provided by smaller reactor size and capacity to achieve reduced design complexity and simplified operation and maintenance requirements, and to provide for incremental capacity increase through multi-module plant clustering. Competitiveness of SMRs depends on the incorporated strategies to overcome loss of economies of scale but equally it depends on finding appropriate market niches for such reactors. For many less developed countries, these are the features of enhanced proliferation resistance and increased robustness of barriers for sabotage protection that may ensure the progress of nuclear power. For such countries, small reactors without on-site refuelling, designed for infrequent replacement of well-contained fuel cassette(s) in a manner that impedes clandestine diversion of nuclear fuel material, may provide a solution. Based on the outputs of recent IAEA activities for innovative SMRs, the paper provides a summary of the state-of-the-art in approaches to improve SMR competitiveness and incorporate enhanced proliferation resistance and energy security. (author)

  16. Design and deployment strategies for small and medium sized reactors (SMRs) to overcome loss of economies of scale and incorporate increased proliferation resistance

    International Nuclear Information System (INIS)

    Kuznetsov, V.

    2007-01-01

    The designers of innovative small and medium sized reactors pursue new design and deployment strategies making use of certain advantages provided by smaller reactor size and capacity to achieve reduced design complexity and simplified operation and maintenance requirements, and to provide for incremental capacity increase through multi-module plant clustering. Competitiveness of SMRs (Small and Medium size Reactor) depends on the incorporated strategies to overcome loss of economies of scale but equally it depends on finding appropriate market niches for such reactors. For many less developed countries, these are the features of enhanced proliferation resistance and increased robustness of barriers for sabotage protection that may ensure the progress of nuclear power. For such countries, small reactors without on-site refuelling, designed for infrequent replacement of well-contained fuel cassette(s) in a manner that impedes clandestine diversion of nuclear fuel material, may provide a solution. Based on the outputs of recent IAEA activities for innovative SMRs, the paper provides a summary of the state-of-the-art in approaches to improve SMR competitiveness and incorporate enhanced proliferation resistance and energy security. (author)

  17. Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1.

    Science.gov (United States)

    Zsebik, Barbara; Citri, Ami; Isola, Jorma; Yarden, Yosef; Szöllosi, János; Vereb, György

    2006-04-15

    ErbB2, a member of the EGF receptor family of tyrosine kinases is overexpressed on many tumor cells of epithelial origin and is the molecular target of trastuzumab (Herceptin), the first humanized antibody used in the therapy of solid tumors. Trastuzumab, which is thought to act, at least in part, by downregulating ErbB2 expression is only effective in approximately 30-40% of ErbB2 positive breast tumors. Geldanamycin and its derivative 17-AAG are potential antitumor agents capable of downregulating client proteins of Hsp90, including ErbB2. To investigate the ability of 17-AAG to downregulate ErbB2 in trastuzumab resistant breast cancer cells and the possibility of 17-AAG and trastuzumab potentiating each other's effect, the recently established trastuzumab resistant breast cancer cell line, JIMT-1 was compared to the known trastuzumab sensitive SKBR-3 line. Baseline and stimulus-evoked dimerization and activation levels of ErbB2, and the effects of trastuzumab and 17-AAG alone and in combination on cell proliferation and apoptosis, as well as on ErbB2 expression and phosphorylation have been measured. Baseline activation and amenability to activation and downregulation by trastuzumab was much lower in the resistant line. However, 17-AAG enhanced ErbB2 homodimerization after 5-10 min of treatment in both cell lines, and decreased proliferation with an IC50 of 70 nM for SKBR-3 and 10nM for JIMT-1. Thus, 17-AAG may be a useful drug in trastuzumab resistant ErbB2 overexpressing tumors. The antiproliferative effect of 17-AAG was positively correlated with phosphorylation and downregulation of ErbB2 and was dominated by apoptosis, although, especially at higher doses, necrosis was also present. Interestingly, IC50 values for ErbB2 downregulation and phosphorylation, in the 30-40 nM range, were not significantly different for the two cell lines. This observation and the negative correlation between resting ErbB2 levels and the antiproliferative effect of 17-AAG may

  18. Over-expression of 60s ribosomal L23a is associated with cellular proliferation in SAG resistant clinical isolates of Leishmania donovani.

    Directory of Open Access Journals (Sweden)

    Sanchita Das

    Full Text Available Sodium antimony gluconate (SAG unresponsiveness of Leishmania donovani (Ld had effectively compromised the chemotherapeutic potential of SAG. 60s ribosomal L23a (60sRL23a, identified as one of the over-expressed protein in different resistant strains of L.donovani as observed with differential proteomics studies indicates towards its possible involvement in SAG resistance in L.donovani. In the present study 60sRL23a has been characterized for its probable association with SAG resistance mechanism.The expression profile of 60s ribosomal L23a (60sRL23a was checked in different SAG resistant as well as sensitive strains of L.donovani clinical isolates by real-time PCR and western blotting and was found to be up-regulated in resistant strains. Ld60sRL23a was cloned, expressed in E.coli system and purified for raising antibody in swiss mice and was observed to have cytosolic localization in L.donovani. 60sRL23a was further over-expressed in sensitive strain of L.donovani to check its sensitivity profile against SAG (Sb V and III and was found to be altered towards the resistant mode.This study reports for the first time that the over expression of 60sRL23a in SAG sensitive parasite decreases the sensitivity of the parasite towards SAG, miltefosine and paramomycin. Growth curve of the tranfectants further indicated the proliferative potential of 60sRL23a assisting the parasite survival and reaffirming the extra ribosomal role of 60sRL23a. The study thus indicates towards the role of the protein in lowering and redistributing the drug pressure by increased proliferation of parasites and warrants further longitudinal study to understand the underlying mechanism.

  19. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China); Wang, Yuchan, E-mail: wangyuchannt@126.com [Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu (China); He, Song, E-mail: hesongnt@126.com [Department of Pathology, Affiliated Cancer Hospital of Nantong University, 30 North Tongyang Road, Pingchao, Nantong 226361, Jiangsu (China)

    2015-07-15

    Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

  20. Optimization of Heterogeneous Fuel Designs for Utilization of Thorium In PWRs To Enhance Proliferation Resistance and Reduce Waste

    International Nuclear Information System (INIS)

    Todosow, M.; Galperin, A.

    2002-01-01

    This paper presents a summary of the first stage of the project aimed to examine heterogeneous core design options for the implementation of the thorium- 233 U fuel cycle in pressurized water reactors (PWRs) and to identify the core design and fuel management strategies that will maximize the benefits from inclusion of thorium in the fuel. The project is carried out within a framework of Nuclear Energy Research Initiative (NERI) supported by the US Department of Energy (1). Principal investigators are M. Todosow from Brookhaven National Laboratory and M. Kazimi from Massachusetts Institute of Technology with contributions from Kurchatov Institute (Russia) and Ben-Gurion University of the Negev (Israel). The fuel cycle assessment concentrates on key measures of performance in several important areas including proliferation characteristics of the spent fuel, reliability, safety, cost, environmental impact, and licensing issues

  1. Silencing CAPN2 Expression Inhibited Castration-Resistant Prostate Cancer Cells Proliferation and Invasion via AKT/mTOR Signal Pathway

    Directory of Open Access Journals (Sweden)

    Pu Li

    2017-01-01

    Full Text Available The mRNA expression of CAPN2 was upregulated in CRPC cells (DU145 and PC3 than that in non-CRPC cells. Silencing CAPN2 expression could inhibit DU145 and PC3 cells proliferation by cell cycle arrest at G1 phase. Knockdown of CPAN2 level suppressed the migration and invasion capacity of CRPC cells by reducing matrix metalloproteinase-2 (MMP-2 and MMP-9 activation, as well as repressing the phosphorylation protein expression of AKT and mTOR. In addition, we found that the expression of CAPN2 was elevated in Pca tissues than that in normal control tissues. Therefore, we showed the important roles of CAPN2 in the development and progression in CRPC cells, suggesting a new therapeutic intervention for treating castration-resistant prostate cancer patients.

  2. MECHANISMS OF CELL RESISTANCE TO CYTOMEGALOVIRUS ARE CONNECTED WITH CELL PROLIFERATION STATE AND TRANSCRIPTION ACTIVITY OF LEUKOCYTE AND IMMUNE INTERFERON GENES

    Directory of Open Access Journals (Sweden)

    T. M. Sokolova

    2007-01-01

    Full Text Available Abstract. Cytomegalovirus (CMV infection in diploid human fibroblasts (HF and levels of cell resistance to this virus were shown to be in direct correlation with high α-interferon (IFNα gene activity and induction of IFNγ gene transcription. Regulation of IFNα mRNA transcription was revealed to be positively associated with cellular DNA synthesis. At the same time, activities of IFNβ and IFNγ genes were at the constantly low level and were not induced in DNA-synthetic phase (S-phase of the cells. Levels of IFNα mRNA synthesis are quite different for G0- vs S-phase-synchronized HF110044 cell cultures: appropriate values for dividing cells (S-phase proved to be 100-fold higher than in resting state (G0. The mode of CMV infection in resting HF-cell could be considered either as acute, or a productive one. On the contrary, proliferating cells exhibited lagging viral syntheses and delayed cell death. Arrest of CMV replication may be, to some extent, comparable with latent infectious state, being associated with high production of IFNα. Both basal and induced levels of IFNα mRNA in CMV-resistant adult human skin fibroblast cells (HSF-1608 were 10-fold higher than in human embryo lung cell line (HELF-977, which is highly sensitive to CMV. Moreover, a short-time induction of IFNγ genes was observed in resistant cells, whereas no such effect was noticed in highly sensitive cells. CMV reproduction in sensitive cell lines (HELF-977 and HELF-110044 partially inhibits IFNα mRNA transcription at the later stages of infection (24 to 48 hours. Thus, cellular resistance and control of CMV infection in diploid fibroblasts are associated predominantly with high transcription of IFNα gene, and with temporal induction of IFNγ gene. We did not reveal any participation of IFNβ genes in protection of human diploid fibroblasts from CMV.

  3. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Directory of Open Access Journals (Sweden)

    L. Zhao

    2014-01-01

    Full Text Available Fanconi anemia complementation group F protein (FANCF is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  4. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    International Nuclear Information System (INIS)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F.; Zheng, Z.H.; Wang, E.H.; Wei, M.J.

    2013-01-01

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer

  5. Development of the COMPRE-A Program for Evaluating Proliferation Resistance (PR) and Physical Protection (PP) of the Nuclear Facility

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sukhoon; Kim, Juyub; Shin, Kwangyoung [FNC Technology Co., Yongin (Korea, Republic of); Seo, Janghoon; Jang, Sungsoon; Yoo, Hosik [Korea Institute of Nuclear Non-proliferation and Control, Daejeon (Korea, Republic of)

    2016-10-15

    In order to make up for the limitation inherent in these methodologies, a new methodology called 'Comprehensive Methodology for PR and PP Evaluation (COMPRE)' is being developed by the Korea Institute of Nuclear Non-proliferation and Control (KINAC). Currently, a project for improving a computational program implementing the COMPRE methodology is ongoing in KINAC, and the 'COMPRE-A (i.e. COMPRE-Advanced model)' program was developed as part of this project. This paper describes details of the COMPRE-A program developed for establishing the platform corresponding to features of the evaluation factor derived for COMPRE, and for enhancing easiness of the result analysis through embodying the visualization and comparison tools for the evaluation result. As part of the project for improving a computational program implementing the COMPRE methodology, the COMPRE-A program was developed. This program provides not only the platform corresponding to features of the evaluation factor derived for COMPRE but also the visualization and comparison tools for enhancing easiness of the result analysis. The V and V for the developed program was performed through comparison with the result obtained by using MS-Excel for a sample case consisting of three (3) measures, six (6) sections and twenty-six (26) attributes. From the comparison result, it was confirmed that the risk in aspects of PR and PP at nuclear facilities could be quantitatively evaluated within the acceptable range using the COMPRE-A program.

  6. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, L.; Li, N.; Yu, J.K.; Tang, H.T.; Li, Y.L.; He, M.; Yu, Z.J.; Bai, X.F. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Zheng, Z.H.; Wang, E.H. [Institute of Pathology and Pathophysiology, China Medical University, Heping Ward, Shenyang City, Liaoning (China); Wei, M.J. [Department of Pharmacology, School of Pharmacy, China Medical University, Heping Ward, Shenyang City, Liaoning (China)

    2013-12-12

    Fanconi anemia complementation group F protein (FANCF) is a key factor, which maintains the function of FA/BRCA, a DNA damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. We performed a specific FANCF-shRNA knockdown of endogenous FANCF in vitro. Cell viability was measured with a CCK-8 assay. DNA damage was assessed with an alkaline comet assay. Apoptosis, cell cycle, and drug accumulation were measured by flow cytometry. The expression levels of protein were determined by Western blot using specific antibodies. Based on these results, we used cell migration and invasion assays to demonstrate a crucial role for FANCF in those processes. FANCF shRNA effectively inhibited expression of FANCF. We found that proliferation of FANCF knockdown breast cancer cells (MCF-7 and MDA-MB-435S) was significantly inhibited, with cell cycle arrest in the S phase, induction of apoptosis, and DNA fragmentation. Inhibition of FANCF also resulted in decreased cell migration and invasion. In addition, FANCF knockdown enhanced sensitivity to doxorubicin in breast cancer cells. These results suggest that FANCF may be a potential target for molecular, therapeutic intervention in breast cancer.

  7. The glucocorticoid receptor cooperates with the erythropoietin receptor and c-Kit to enhance and sustain proliferation of erythroid progenitors in vitro

    NARCIS (Netherlands)

    von Lindern, M.; Zauner, W.; Mellitzer, G.; Steinlein, P.; Fritsch, G.; Huber, K.; Löwenberg, B.; Beug, H.

    1999-01-01

    Although erythropoietin (Epo) is essential for the production of mature red blood cells, the cooperation with other factors is required for a proper balance between progenitor proliferation and differentiation. In avian erythroid progenitors, steroid hormones cooperate with tyrosine kinase receptors

  8. Environmental enrichment induces behavioral recovery and enhanced hippocampal cell proliferation in an antidepressant-resistant animal model for PTSD.

    Directory of Open Access Journals (Sweden)

    Hendrikus Hendriksen

    Full Text Available BACKGROUND: Post traumatic stress disorder (PTSD can be considered the result of a failure to recover after a traumatic experience. Here we studied possible protective and therapeutic aspects of environmental enrichment (with and without a running wheel in Sprague Dawley rats exposed to an inescapable foot shock procedure (IFS. METHODOLOGY/PRINCIPAL FINDINGS: IFS induced long-lasting contextual and non-contextual anxiety, modeling some aspects of PTSD. Even 10 weeks after IFS the rats showed reduced locomotion in an open field. The antidepressants imipramine and escitalopram did not improve anxiogenic behavior following IFS. Also the histone deacetylase (HDAC inhibitor sodium butyrate did not alleviate the IFS induced immobility. While environmental enrichment (EE starting two weeks before IFS did not protect the animals from the behavioral effects of the shocks, exposure to EE either immediately after the shock or one week later induced complete recovery three weeks after IFS. In the next set of experiments a running wheel was added to the EE to enable voluntary exercise (EE/VE. This also led to reduced anxiety. Importantly, this behavioral recovery was not due to a loss of memory for the traumatic experience. The behavioral recovery correlated with an increase in cell proliferation in hippocampus, a decrease in the tissue levels of noradrenalin and increased turnover of 5-HT in prefrontal cortex and hippocampus. CONCLUSIONS/SIGNIFICANCE: This animal study shows the importance of (physical exercise in the treatment of psychiatric diseases, including post-traumatic stress disorder and points out the possible role of EE in studying the mechanism of recovery from anxiety disorders.

  9. Exploring Reasons for the Resistance to Sustainable Management within Non-Profit Organizations

    Directory of Open Access Journals (Sweden)

    Claus-Heinrich Daub

    2014-05-01

    Full Text Available The numerous empirical and conceptual studies that have been conducted over recent years concerning the social responsibility of enterprises and their contributions towards sustainable development have given very little consideration to non-profit organizations (NPOs. This is surprising, because NPOs are confronted with very similar challenges to profit-orientated enterprises regarding their evolution into sustainable organizations. This paper is a preliminary conceptual study and explores the question of why the corporate social responsibility, or corporate sustainability, of NPOs has to date been both neglected by research establishments and also extensively ignored by the NPOs during their day-to-day practical management. The example of church and pastoral institutions in Germany is used to demonstrate the extent to which they take account of ecological and social aspects in their management systems and processes and, thus, implement sustainable management within their day-to-day practice. The paper concludes with some proposals for further empirical and conceptual research projects, which are designed to analyze developments within NPOs with relation to the integration of sustainability into their management systems and processes.

  10. Association between insulin resistance and sustained virologic response in hepatitis C treatment, genotypes 1 versus 2 and 3: systematic literature review and meta-analysis.

    Science.gov (United States)

    Laurito, Marcela Pezzoto; Parise, Edison Roberto

    2013-01-01

    Controversial results have been found in literature for the association between insulin resistance and sustained virologic response to standard chronic hepatitis C treatment. This study aims to provide a systematic literature review with meta-analysis, in order to evaluate if insulin resistance interferes with sustained virologic response in patients infected by the HCV genotype 1 versus HCV genotypes 2 and 3, undergoing treatment with interferon and ribavirin or pegylated interferon and ribavarin. Systematic search was performed on main electronic databases until May 2012. Primary outcome was sustained virologic response, defined as undetectable levels of HCV-RNA six months after the end of treatment. Meta-analytic measure was estimated using Dersimonian and Laird's method, using Stata software. Thirteen studies involving 2238 infected patients were included. There was a statistically significant association between insulin resistance and lower sustained virologic response rate, and this difference occurred in HCV genotype G1 (OR: 2.23; 95% CI: 1.59-3.13) and G2/G3 (OR: 4.45; 95% CI: 1.59-12.49). In addition, a difference was seen in the cut-offs used for defining insulin resistance by Homeostasis Model Assessment of Insulin Resistance. To minimize this limitation, sub-analysis that excluded the studies that did not use 2 as a cut-off value was performed and the results still demonstrated association between insulin resistance and sustained virologic response, for both genotypic groups. This meta-analysis provides evidence that elevated Homeostasis Model Assessment of Insulin Resistance is associated with a lower sustained virologic response rate in patients with hepatitis C treated with interferon and ribavirin or pegylated interferon and ribavarin, regardless of their genotype. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  11. Environmental and Sustainable Technology Evaluation: Mold-resistant Lonseal flooring--Lonseal, Inc., Lonwood Natural

    Science.gov (United States)

    The test program measured the mold resistance of Lonseal Lonwood Natural flooring. One additional ancillary test for emissions of VOCs and formaldehyde was performed. Lonwood Natural flooring is a sheet vinyl product with an embossed wood-grain texture. Constructed in multiple la...

  12. Bio-based resistance inducers for sustainable plant protection against pathogens

    Czech Academy of Sciences Publication Activity Database

    Burketová, Lenka; Trdá, Lucie; Ott, P.G.; Valentová, O.

    2015-01-01

    Roč. 33, č. 6 (2015), s. 994-1004 ISSN 0734-9750 R&D Projects: GA MŠk(CZ) LD14056 Institutional support: RVO:61389030 Keywords : Induced resistance * Elicitor * Chitosan Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 9.848, year: 2015

  13. Sustained low prevalence of meticillin-resistant Staphylococcus aureus upon admission to hospital in The Netherlands

    NARCIS (Netherlands)

    Bode, L. G. M.; Wertheim, H. F. L.; Kluytmans, J. A. J. W.; Bogaers-Hofman, D.; Vandenbroucke-Grauls, C. M. J. E.; Roosendaal, R.; Troelstra, A.; Box, A. T. A.; Voss, A.; van Belkum, A.; Verbrugh, H. A.; Vos, M. C.

    2011-01-01

    The prevalence of meticillin-resistant Staphylococcus aureus (MRSA) carriage at hospital admission in The Netherlands was 0.03% in 1999-2000. The aim of the present study was to assess whether the prevalence of MRSA carriage in The Netherlands has changed over the last few years. In five Dutch

  14. Influence of sustained deworming pressure on the anthelmintic resistance status in strongyles of sheep under field conditions.

    Science.gov (United States)

    Vijayasarathi, M K; Sreekumar, C; Venkataramanan, R; Raman, M

    2016-10-01

    Anthelmintic resistance (AR) status in Madras Red sheep from selected field flocks of a government funded scheme, covered by regular, sustained anthelmintic treatment for more than 10 years was determined. Parameters such as fecal egg count reduction test (FECRT), larval paralysis assay (LPA), and allele-specific-PCR (AS-PCR) were used to test the efficacy of fenbendazole, tetramisole, and ivermectin at recommended doses, in two seasons. Sheep belonging to non-beneficiary farmers were used as controls. Mean FECRT values of beneficiary group during winter and summer seasons were 77.77 and 76.04, 93.65 and 92.12, and 95.37 and 98.06 %, respectively, for fenbendazole, tetramisole, and ivermectin. In the non-beneficiary groups, the corresponding values were 74.82 and 81.09 %, 96.05 and 97.40 %, and 97.26 and 98.23 %, respectively. The results revealed resistance to fenbendazole, suspect resistance to tetramisole and susceptibility to ivermectin in beneficiary flock. In non-beneficiary flock, while resistance was noticed against fenbendazole, both tetramisole and ivermectin were effective. FECR values were found to be significantly different between beneficiary and non-beneficiary groups against tetramisole. The results of LPA confirmed this finding, as 50 % of the Haemonchus contortus larvae were paralyzed at the concentration of 0.0156 μg/ml in the beneficiary group, while those of non-beneficiary groups required lower concentrations of 0.0078 μg/ml. AS-PCR revealed the predominance of heterozygous susceptible population of H. contortus in the beneficiary group. In this study, resistance to fenbendazole was confirmed in both the beneficiary and non-beneficiary groups and this could be attributed to frequent use of benzimidazoles as seen from the deworming records. Emergence of tetramisole resistance was detected in the beneficiary group, where the drug was used continuously for 4 years. Ivermectin was found to be effective in all the flocks. It is

  15. Phosphatidylinositol 3-Kinase (PI3K) Activity Bound to Insulin-like Growth Factor-I (IGF-I) Receptor, which Is Continuously Sustained by IGF-I Stimulation, Is Required for IGF-I-induced Cell Proliferation*

    Science.gov (United States)

    Fukushima, Toshiaki; Nakamura, Yusaku; Yamanaka, Daisuke; Shibano, Takashi; Chida, Kazuhiro; Minami, Shiro; Asano, Tomoichiro; Hakuno, Fumihiko; Takahashi, Shin-Ichiro

    2012-01-01

    Continuous stimulation of cells with insulin-like growth factors (IGFs) in G1 phase is a well established requirement for IGF-induced cell proliferation; however, the molecular components of this prolonged signaling pathway that is essential for cell cycle progression from G1 to S phase are unclear. IGF-I activates IGF-I receptor (IGF-IR) tyrosine kinase, followed by phosphorylation of substrates such as insulin receptor substrates (IRS) leading to binding of signaling molecules containing SH2 domains, including phosphatidylinositol 3-kinase (PI3K) to IRS and activation of the downstream signaling pathways. In this study, we found prolonged (>9 h) association of PI3K with IGF-IR induced by IGF-I stimulation. PI3K activity was present in this complex in thyrocytes and fibroblasts, although tyrosine phosphorylation of IRS was not yet evident after 9 h of IGF-I stimulation. IGF-I withdrawal in mid-G1 phase impaired the association of PI3K with IGF-IR and suppressed DNA synthesis the same as when PI3K inhibitor was added. Furthermore, we demonstrated that Tyr1316-X-X-Met of IGF-IR functioned as a PI3K binding sequence when this tyrosine is phosphorylated. We then analyzed IGF signaling and proliferation of IGF-IR−/− fibroblasts expressing exogenous mutant IGF-IR in which Tyr1316 was substituted with Phe (Y1316F). In these cells, IGF-I stimulation induced tyrosine phosphorylation of IGF-IR and IRS-1/2, but mutated IGF-IR failed to bind PI3K and to induce maximal phosphorylation of GSK3β and cell proliferation in response to IGF-I. Based on these results, we concluded that PI3K activity bound to IGF-IR, which is continuously sustained by IGF-I stimulation, is required for IGF-I-induced cell proliferation. PMID:22767591

  16. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    Science.gov (United States)

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  17. 1D resistivity inversion technique in the mapping of igneous intrusives; A step to sustainable quarry development

    Directory of Open Access Journals (Sweden)

    M.A. Nwachukwu

    2017-01-01

    Full Text Available The use of trial pits as a first step in quarry site development causes land degradation and results in more failure than success for potential quarry investors in some parts of the world. In this paper, resistivity, depth and distance values derived from 26 Vertical Electric Soundings (VES and 2 profiling inversion sections were successfully used to evaluate a quarry site prior to development. The target rock Diabase (Dolerite was observed and it had a resistivity range of 3.0 × 104 –7. 8 × 106 Ω-m, and was clearly distinguishable from associated rocks with its bright red color code on the AGI 1D inversion software. This target rock was overlain by quartzite, indurate shale and mudstone as overburden materials. The quartzite, with its off-red colour, has a resistivity range of 2.0 × 103–2.9 × 105 Ω-m, while the indurate shale, with a yellowish-brown colour, showed resistivity values ranging from 6.1 × 102 – 2.8 × 105 Ω-m. Topsoil was clayey, with a resistivity range from 8 – 8.6 × 102u Ω-m and depths of 0.3–1.8 m, often weathered and replaced by associated rocks outcrops. The diabase rock, in the three prospective pits mapped, showed thicknesses of between 40 and 76 m across the site. The prospective pits were identified to accommodate an estimated 2,569,450 tonnes of diabase with an average quarry pit depth of 50 m. This figure was justified by physical observations made at a nearby quarry pit and from test holes. Communities were able to prepare a geophysical appraisal of the intrusive body in their domain for economic planning and sustainability of the natural resource.

  18. Detection of resistance mutations and CD4 slopes in individuals experiencing sustained virological failure

    DEFF Research Database (Denmark)

    Schultze, Anna; Paredes, Roger; Sabin, Caroline

    2014-01-01

    during the episode were included. Mutations were identified using the IAS-US (2013) list, and were presumed to be present from detection until the end of an episode. Multivariable linear mixed models with a random intercept and slope adjusted for age, baseline CD4 count, hepatitis C, drug type, RNA (log...... mutations on CD4 slopes in patients undergoing episodes of viral failure. MATERIALS AND METHODS: Patients from the EuroSIDA and UK CHIC cohorts undergoing at least one episode of virological failure (>3 consecutive RNA measurements >500 on ART) with at least three CD4 measurements and a resistance test......-scale), risk group and subtype were used to estimate CD4 slopes. Individual mutations with a population prevalence of >10% were tested for their effect on the CD4 slope. RESULTS: A total of 2731 patients experiencing a median of 1 (range 1-4) episodes were included in this analysis. The prevalence of any...

  19. Position paper on nuclear proliferation issues preventing nuclear proliferation. A duty for the nuclear community

    Energy Technology Data Exchange (ETDEWEB)

    Goldschmidt, Pierre; Bonin, Bernard [ENS High Scientific Council, Brussels (Belgium)

    2010-06-15

    The production of electricity from nuclear power plants is widely seen today as having an increasing role to play in meeting global energy requirements in a sustainable manner. Conscious of the inherently sensitive nature of nuclear technology and materials the ENS-HSC (European Nuclear Society - High Scientific Council) is well aware that a severe safety, security, environmental or proliferation mishap stemming from nuclear energy anywhere in the world would undermine the potential for nuclear energy to contribute to the global energy supply and the minimization of harmful carbon emissions. While the safety of nuclear power plants has continuously improved over the last three decades, the same degree of success cannot be claimed when it comes to the achievements of the international community in stemming the risk of nuclear weapons proliferation. This unfortunate situation is due to both technical and political reasons. The European nuclear industry is committed to the exclusively peaceful use of nuclear energy and to export nuclear facilities and related materials, equipment and technology solely in accordance with relevant national export laws and regulations, Nuclear Suppliers Group guidelines and pertinent United Nations Security Council Resolutions. The ENS-HSC considers that, as a manifestation of their strong commitment to nonproliferation, it is important for the nuclear industry to pay special attention to and promote proliferation-resistant designs and to take IAEA safeguards requirements into account at the design stage. Preventing nuclear proliferation is primarily the responsibility of states but, as major stakeholders, the nuclear industry and scientific community should actively support nuclear disarmament as foreseen in the Non-Proliferation Treaty and measures necessary to strengthen the non-proliferation regime, particularly the international control of the flux of nuclear material and technology. (orig.)

  20. Position paper on nuclear proliferation issues preventing nuclear proliferation. A duty for the nuclear community

    International Nuclear Information System (INIS)

    Goldschmidt, Pierre; Bonin, Bernard

    2010-01-01

    The production of electricity from nuclear power plants is widely seen today as having an increasing role to play in meeting global energy requirements in a sustainable manner. Conscious of the inherently sensitive nature of nuclear technology and materials the ENS-HSC (European Nuclear Society - High Scientific Council) is well aware that a severe safety, security, environmental or proliferation mishap stemming from nuclear energy anywhere in the world would undermine the potential for nuclear energy to contribute to the global energy supply and the minimization of harmful carbon emissions. While the safety of nuclear power plants has continuously improved over the last three decades, the same degree of success cannot be claimed when it comes to the achievements of the international community in stemming the risk of nuclear weapons proliferation. This unfortunate situation is due to both technical and political reasons. The European nuclear industry is committed to the exclusively peaceful use of nuclear energy and to export nuclear facilities and related materials, equipment and technology solely in accordance with relevant national export laws and regulations, Nuclear Suppliers Group guidelines and pertinent United Nations Security Council Resolutions. The ENS-HSC considers that, as a manifestation of their strong commitment to nonproliferation, it is important for the nuclear industry to pay special attention to and promote proliferation-resistant designs and to take IAEA safeguards requirements into account at the design stage. Preventing nuclear proliferation is primarily the responsibility of states but, as major stakeholders, the nuclear industry and scientific community should actively support nuclear disarmament as foreseen in the Non-Proliferation Treaty and measures necessary to strengthen the non-proliferation regime, particularly the international control of the flux of nuclear material and technology. (orig.)

  1. Proliferation risks

    International Nuclear Information System (INIS)

    Carchon, R.

    1998-09-01

    The report gives an overview of different aspects related to safeguards of fissile materials. Existing treaties including the Non-Proliferation Treaty, and the Tlatelolco and the Rarotonga Treaties are discussed. An overview of safeguards systems for the control of fissile materials as well as the role of various authorities is given. An overall overview of proliferation risks, the physical protection of fissile materials and the trade in fissile materials is given. Finally, the status in problem countries and de facto nuclear weapon states is discussed

  2. Large time-dependent coercivity and resistivity modification under sustained voltage application in a Pt/Co/AlOx/Pt junction.

    NARCIS (Netherlands)

    Brink, van den A.; van der Heijden, M.A.J.; Swagten, H.J.M.; Koopmans, B.

    2015-01-01

    The coercivity and resistivity of a Pt/Co/AlOx/Pt junction are measured under sustained voltage application. High bias voltages of either polarity are determined to cause a strongly enhanced, reversible coercivity modification compared to low voltages. Time-resolved measurements show a logarithmic

  3. Peroxisome Proliferator Activated Receptor-α/Hypoxia Inducible Factor-1α Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells

    Science.gov (United States)

    Papi, Alessio; Storci, Gianluca; Guarnieri, Tiziana; De Carolis, Sabrina; Bertoni, Sara; Avenia, Nicola; Sanguinetti, Alessandro; Sidoni, Angelo; Santini, Donatella; Ceccarelli, Claudio; Taffurelli, Mario; Orlandi, Marina; Bonafé, Massimiliano

    2013-01-01

    Aims Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells “inflammatory addiction” leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. Methods Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines. Mammospheres were exposed to the supernatant of breast tumor and normal mammary gland tissue fibroblasts. Results In mammospheres exposed to the breast tumor fibroblasts supernatant, autocrine tumor necrosis factor-α signalling engenders the functional interplay between peroxisome proliferator activated receptor-α and hypoxia inducible factor-1α (PPARα/HIF1α). The two proteins promote mammospheres formation and enhance each other expression via miRNA130b/miRNA17-5p-dependent mechanism which is antagonized by PPARγ. Further, the PPARα/HIF1α interplay regulates the expression of the pro-inflammatory cytokine interleukin-6, the hypoxia survival factor carbonic anhydrase IX and the plasma lipid carrier apolipoprotein E. Conclusion Our data demonstrate the importance of exploring the role of nuclear receptors (PPARα/PPARγ) in the regulation of pro-inflammatory pathways, with the aim to thwart breast cancer stem cells functioning. PMID:23372804

  4. Nuclear proliferation

    International Nuclear Information System (INIS)

    Stencel, S.

    1978-01-01

    The terms and reactions to President Carter's nuclear policy, culminating in the 1978 Nuclear Non-Proliferation Act, are reviewed and analyzed. The new law increases restrictions on nuclear exports, encourages continued use of light water reactors in preference to plutonium-fueled reactors, and emphasizes technical solutions to proliferation problems. Critics of the law point out that it will hurt U.S. trade unfairly, that other countries do not have as many fuel options as the U.S. has, and that nuclear sales have as many political and economic as technical solutions. Compromise areas include new international safety guidelines, the possibility of an international nuclear fuel bank, and a willingness to consider each case on its merits. 21 references

  5. The international nuclear non-proliferation system

    International Nuclear Information System (INIS)

    Simpson, J.; McGrew, T.

    1985-01-01

    This volume focuses upon the issues raised at this Conference, and attempts to address the international diplomatic, political and trading, rather than technical, questions which surround nuclear non-proliferation policies. It does so by bringing together chapters contributed by participants in non-proliferation diplomacy, those with experience in shaping International Atomic Energy Agency and national policies and academic observers of non-proliferation activities and the international nuclear industry. An analysis is provided of past non-proliferation policies and activities and current issues, and an attempt is made to offer ideas for new initiatives which may sustain the non-proliferation system in the future

  6. The different expression of TRPM7 and MagT1 impacts on the proliferation of colon carcinoma cells sensitive or resistant to doxorubicin

    OpenAIRE

    Cazzaniga, Alessandra; Moscheni, Claudia; Trapani, Valentina; Wolf, Federica I.; Farruggia, Giovanna; Sargenti, Azzurra; Iotti, Stefano; Maier, Jeanette A. M.; Castiglioni, Sara

    2017-01-01

    The processes leading to anticancer drug resistance are not completely unraveled. To get insights into the underlying mechanisms, we compared colon carcinoma cells sensitive to doxorubicin with their resistant counterpart. We found that resistant cells are growth retarded, and show staminal and ultrastructural features profoundly different from sensitive cells. The resistant phenotype is accompanied by the upregulation of the magnesium transporter MagT1 and the downregulation of the ion chann...

  7. Riboflavin Depletion Promotes Tumorigenesis in HEK293T and NIH3T3 Cells by Sustaining Cell Proliferation and Regulating Cell Cycle-Related Gene Transcription.

    Science.gov (United States)

    Long, Lin; He, Jian-Zhong; Chen, Ye; Xu, Xiu-E; Liao, Lian-Di; Xie, Yang-Min; Li, En-Min; Xu, Li-Yan

    2018-05-07

    Riboflavin is an essential component of the human diet and its derivative cofactors play an established role in oxidative metabolism. Riboflavin deficiency has been linked with various human diseases. The objective of this study was to identify whether riboflavin depletion promotes tumorigenesis. HEK293T and NIH3T3 cells were cultured in riboflavin-deficient or riboflavin-sufficient medium and passaged every 48 h. Cells were collected every 5 generations and plate colony formation assays were performed to observe cell proliferation. Subcutaneous tumorigenicity assays in NU/NU mice were used to observe tumorigenicity of riboflavin-depleted HEK293T cells. Mechanistically, gene expression profiling and gene ontology analysis were used to identify abnormally expressed genes induced by riboflavin depletion. Western blot analyses, cell cycle analyses, and chromatin immunoprecipitation were used to validate the expression of cell cycle-related genes. Plate colony formation of NIH3T3 and HEK293T cell lines was enhanced >2-fold when cultured in riboflavin-deficient medium for 10-20 generations. Moreover, we observed enhanced subcutaneous tumorigenicity in NU/NU mice following injection of riboflavin-depleted compared with normal HEK293T cells (55.6% compared with 0.0% tumor formation, respectively). Gene expression profiling and gene ontology analysis revealed that riboflavin depletion induced the expression of cell cycle-related genes. Validation experiments also found that riboflavin depletion decreased p21 and p27 protein levels by ∼20%, and increased cell cycle-related and expression-elevated protein in tumor (CREPT) protein expression >2-fold, resulting in cyclin D1 and CDK4 levels being increased ∼1.5-fold, and cell cycle acceleration. We also observed that riboflavin depletion decreased intracellular riboflavin levels by 20% and upregulated expression of riboflavin transporter genes, particularly SLC52A3, and that the changes in CREPT and SLC52A3 correlated with

  8. MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin

    International Nuclear Information System (INIS)

    Zhang, Zi-wei; Guo, Rui-wei; Lv, Jin-lin; Wang, Xian-mei; Ye, Jin-shan; Lu, Ni-hong; Liang, Xing; Yang, Li-xia

    2017-01-01

    Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis. - Highlights: • Suggesting a new mechanism of insulin-triggered VSMC functions. • Providing a new therapeutic strategies that target atherosclerosis in T2DM patients. • Providing a new strategies that target in-stent restenosis in T2DM patients.

  9. Interferon-γ-inducible protein-10 in chronic hepatitis C: Correlations with insulin resistance, histological features & sustained virological response.

    Science.gov (United States)

    Crisan, Dana; Grigorescu, Mircea Dan; Radu, Corina; Suciu, Alina; Grigorescu, Mircea

    2017-04-01

    One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology. Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed. A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR. Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.

  10. Effects of Combined Training with Breathing Resistance and Sustained Physical Exertion to Improve Endurance Capacity and Respiratory Muscle Function in Healthy Young Adults

    OpenAIRE

    Kido, Satoshi; Nakajima, Yasuhiro; Miyasaka, Tomoya; Maeda, Yusuke; Tanaka, Toshiaki; Yu, Wenwei; Maruoka, Hiroshi; Takayanagi, Kiyomi

    2013-01-01

    [Purpose] In this study, combined training with breathing resistance and sustained physical exertion was carried out to evaluate its physiological effects and its effect on improve endurance capacity. [Subjects and Methods] The subjects were nine healthy adults (mean age 20.4, SD ? 1.7?years). The combined training group (n = 5) carried out 6 weeks of combined training using a cycle ergometer, with exercise load tests and respiratory function tests performed before and after the training. The...

  11. Sustainability of Advanced Fuel Cycles

    International Nuclear Information System (INIS)

    Kuznetsov, Vladimir

    2013-01-01

    ⇒ The IAEA’s International Project on Innovative Nuclear Reactors and Fuel Cycles (INPRO) was established in 2000. ⇒ INPRO cooperates with Member States to ensure that sustainable nuclear energy is available to help meet the energy needs of the 21st century. ⇒ INPRO is part of the integrated services of the IAEA provided to Member States considering initial development or expansion of nuclear energy programmes. ⇒ INPRO Methodology for nuclear energy system assessment - a comprehensive set of internationally agreed basic principles, requirements and criteria in the important areas of economics, safety, waste management, proliferation resistance, physical protection, environment and infrastructure. ⇒ Meeting the INPRO criteria in all of the areas ensures sustainability of nuclear energy system and its high potential to meet growing energy demand throughout the present century

  12. Preventing proliferation

    International Nuclear Information System (INIS)

    Rathjens, G.

    1983-01-01

    Challenging the argument that nuclear proliferation may be stabilizing, the author cites the Israeli attack on Iraq as evidence that emergent nuclear states may be moved to attack their adversaries.The larger the number of decision makers who can unleash nuclear weapons, the greater the liklihood of their use. Several reasons are cited for nations to seek nuclear capability: the accelerated spread of technology, the deterioration in US-Soviet relations and strength relative to their nations, the high cost of conventional weapons, and a loss of confidence in the international safeguards system. The imposition of constraints, such as a Comprehensive Test Ban Treaty, on nuclear trade and technology transfer are likely to have a high cost. The US position on this issue is likely to be determined by the balance of power with the Soviet Union. 5 references

  13. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  14. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing options ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, ...

  15. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Animal & Veterinary Safety & Health Antimicrobial Resistance Animation of Antimicrobial Resistance Share Tweet Linkedin Pin it More sharing ... CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over ...

  16. Over-expression of CHAF1A promotes cell proliferation and apoptosis resistance in glioblastoma cells via AKT/FOXO3a/Bim pathway

    International Nuclear Information System (INIS)

    Peng, Honghai; Du, Bin; Jiang, Huili; Gao, Jun

    2016-01-01

    Chromatinassembly factor 1 subunit A (CHAF1A) has been reported to be involved in several human diseases including cancer. However, the biological and clinical significance of CHAF1A in glioblastoma progression remains largely unknown. In this study, we found that up-regulation of CHAF1A happens frequently in glioblastoma tissues and is associated with glioblastoma prognosis. Knockout of CHAF1A by CRISPR/CAS9 technology induce G1 phase arrest and apoptosis in glioblastoma cell U251 and U87. In addition, inhibition of CHAF1A influenced the signal transduction of the AKT/FOXO3a/Bim axis, which is required for glioblastoma cell proliferation. Taken together, these results show that CHAF1A contributes to the proliferation of glioblastoma cells and may be developed as a de novo drug target and prognosis biomarker of glioblastoma.

  17. Over-expression of CHAF1A promotes cell proliferation and apoptosis resistance in glioblastoma cells via AKT/FOXO3a/Bim pathway

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Honghai; Du, Bin [Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China); Jiang, Huili [Friendship Nephrology and Blood Purification Center, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China); Gao, Jun, E-mail: gaoj1666@126.com [Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013 (China)

    2016-01-22

    Chromatinassembly factor 1 subunit A (CHAF1A) has been reported to be involved in several human diseases including cancer. However, the biological and clinical significance of CHAF1A in glioblastoma progression remains largely unknown. In this study, we found that up-regulation of CHAF1A happens frequently in glioblastoma tissues and is associated with glioblastoma prognosis. Knockout of CHAF1A by CRISPR/CAS9 technology induce G1 phase arrest and apoptosis in glioblastoma cell U251 and U87. In addition, inhibition of CHAF1A influenced the signal transduction of the AKT/FOXO3a/Bim axis, which is required for glioblastoma cell proliferation. Taken together, these results show that CHAF1A contributes to the proliferation of glioblastoma cells and may be developed as a de novo drug target and prognosis biomarker of glioblastoma.

  18. Bisphenol A activates EGFR and ERK promoting proliferation, tumor spheroid formation and resistance to EGFR pathway inhibition in estrogen receptor negative inflammatory breast cancer cells

    Science.gov (United States)

    Background: Inflammatory breast cancer (IBC) is a distinct and the deadliest breast cancer variant, which shows a rapid rate of progression and acquired therapeutic resistance. Epidemiological studies suggest that chemical exposure in the environment and consumer products can aff...

  19. Sustained Interleukin-1β Exposure Modulates Multiple Steps in Glucocorticoid Receptor Signaling, Promoting Split-Resistance to the Transactivation of Prominent Anti-Inflammatory Genes by Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Pedro Escoll

    2015-01-01

    Full Text Available Clinical treatment with glucocorticoids (GC can be complicated by cytokine-induced glucocorticoid low-responsiveness (GC-resistance, GCR, a condition associated with a homogeneous reduction in the expression of GC-receptor- (GR- driven anti-inflammatory genes. However, GR level and phosphorylation changes modify the expression of individual GR-responsive genes differently. As sustained IL-1β exposure is key in the pathogenesis of several major diseases with prevalent GCR, we examined GR signaling and the mRNA expression of six GR-driven genes in cells cultured in IL-1β and afterwards challenged with GC. After a GC challenge, sustained IL-1β exposure reduced the cytoplasmic GR level, GRSer203 and GRSer211 phosphorylation, and GR nuclear translocation and led to selective GCR in the expression of the studied genes. Compared to GC alone, in a broad range of GC doses plus sustained IL-1β, FKBP51 mRNA expression was reduced by 1/3, TTP by 2/3, and IRF8 was completely knocked down. In contrast, high GC doses did not change the expression of GILZ and DUSP1, while IGFBP1 was increased by 5-fold. These effects were cytokine-selective, IL-1β dose- and IL-1R1-dependent. The integrated gain and loss of gene functions in the “split GCR” model may provide target cells with a survival advantage by conferring resistance to apoptosis, chemotherapy, and GC.

  20. Fissile material disposition and proliferation risk

    Energy Technology Data Exchange (ETDEWEB)

    Dreicer, J.S.; Rutherford, D.A. [Los Alamos National Lab., NM (United States). NIS Div.

    1996-05-01

    The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium.

  1. Fissile material disposition and proliferation risk

    International Nuclear Information System (INIS)

    Dreicer, J.S.; Rutherford, D.A.

    1996-01-01

    The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium

  2. Nicotine promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells.

    Science.gov (United States)

    Wang, Yan Yan; Liu, Yao; Ni, Xiao Yan; Bai, Zhen Huan; Chen, Qiong Yun; Zhang, Ye; Gao, Feng Guang

    2014-03-01

    Although nicotine is a risk factor for carcinogenesis and atherosclerosis, epidemiological data indicate that nicotine has therapeutic benefits in treating Alzheimer's disease. Our previous studies also showed that nicotine-treated dendritic cells have potential antitumor effects. Hence, the precise effects of nicotine on the biological characterizations of cells are controversial. The aim of the present study was to assess the roles of α7 nicotinic acetylcholine receptors (nAChRs), Erk1/2-p38-JNK and PI3K-Akt pathway in nicotine-mediated proliferation and anti-apoptosis effects. The results firstly showed that nicotine treatment clearly augmented cell viability and upregulated PCNA expression in both Raw264.7 and El4 cells. Meanwhile, nicotine afforded protection against cisplatin-induced toxicity through inhibiting caspase-3 activation and upregulating anti-apoptotic protein expression. Further exploration demonstrated that nicotine efficiently abolished cisplatin-promoted mitochondria translocation of Bax and the release of cytochrome c. The pretreatment of α-bungarotoxin and tubocurarine chloride significantly attenuated nicotine-augmented cell viability, abolished caspase-3 activation and α7 nAChR upregulation. Both Erk-JNK-p38 and PI3K-Akt signaling pathways could be activated by nicotine treatment in Raw264.7 and El4 cells. Notably, when Erk-JNK and PI3K-Akt activities were inhibited, nicotine-augmented cell proliferation and anti-apoptotic effects were abolished accordingly. The results presented here indicate that nicotine could achieve α7 nAChR-mediated proliferation and anti-apoptotic effects by activating Erk-JNK and PI3K-Akt pathways respectively, providing potential therapeutic molecules to deal with smoking-associated human diseases.

  3. Internal Tandem Duplication in FLT3 Attenuates Proliferation and Regulates Resistance to the FLT3 Inhibitor AC220 by Modulating p21Cdkn1a and Pbx1 in Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Mariko Abe

    Full Text Available Internal tandem duplication (ITD mutations in the Fms-related tyrosine kinase 3 (FLT3 gene (FLT3-ITD are associated with poor prognosis in patients with acute myeloid leukemia (AML. Due to the development of drug resistance, few FLT3-ITD inhibitors are effective against FLT3-ITD+ AML. In this study, we show that FLT3-ITD activates a novel pathway involving p21Cdkn1a (p21 and pre-B cell leukemia transcription factor 1 (Pbx1 that attenuates FLT3-ITD cell proliferation and is involved in the development of drug resistance. FLT3-ITD up-regulated p21 expression in both mouse bone marrow c-kit+-Sca-1+-Lin- (KSL cells and Ba/F3 cells. The loss of p21 expression enhanced growth factor-independent proliferation and sensitivity to cytarabine as a consequence of concomitantly enriching the S+G2/M phase population and significantly increasing the expression of Pbx1, but not Evi-1, in FLT3-ITD+ cells. This enhanced cell proliferation following the loss of p21 was partially abrogated when Pbx1 expression was silenced in FLT3-ITD+ primary bone marrow colony-forming cells and Ba/F3 cells. When FLT3-ITD was antagonized with AC220, a selective inhibitor of FLT3-ITD, p21 expression was decreased coincident with Pbx1 mRNA up-regulation and a rapid decline in the number of viable FLT3-ITD+ Ba/F3 cells; however, the cells eventually became refractory to AC220. Overexpressing p21 in FLT3-ITD+ Ba/F3 cells delayed the emergence of cells that were refractory to AC220, whereas p21 silencing accelerated their development. These data indicate that FLT3-ITD is capable of inhibiting FLT3-ITD+ cell proliferation through the p21/Pbx1 axis and that treatments that antagonize FLT3-ITD contribute to the subsequent development of cells that are refractory to a FLT3-ITD inhibitor by disrupting p21 expression.

  4. Veterans Affairs methicillin-resistant Staphylococcus aureus prevention initiative associated with a sustained reduction in transmissions and health care-associated infections.

    Science.gov (United States)

    Evans, Martin E; Kralovic, Stephen M; Simbartl, Loretta A; Freyberg, Ron W; Obrosky, D Scott; Roselle, Gary A; Jain, Rajiv

    2013-11-01

    Implementation of a methicillin-resistant Staphylococcus aureus (MRSA) Prevention Initiative was associated with significant declines in MRSA transmission and MRSA health care-associated infection rates in Veterans Affairs acute care facilities nationwide in the 33-month period from October 2007 through June 2010. Here, we show continuing declines in MRSA transmissions (P = .004 for trend, Poisson regression) and MRSA health care-associated infections (P < .001) from July 2010 through June 2012. The Veterans Affairs Initiative was associated with these effects, sustained over 57 months, in a large national health care system. Published by Mosby, Inc.

  5. Increased expression of bHLH transcription factor E2A (TCF3) in prostate cancer promotes proliferation and confers resistance to doxorubicin induced apoptosis

    International Nuclear Information System (INIS)

    Patel, Divya; Chaudhary, Jaideep

    2012-01-01

    Highlights: ► E2A, considered as a tumor suppressor is highly expressed in prostate cancer. ► Silencing of E2A attenuates cell proliferation and promotes apoptosis. ► E2A regulates c-myc, Id1, Id3 and CDKN1A expression. ► Loss of E2A promotes doxorubicin dependent apoptosis in prostate cancer cells. ► Results suggest that E2A acts as a tumor promoter at least in prostate cancer. -- Abstract: E2A (TCF3) is a multifunctional basic helix loop helix (bHLH), transcription factor. E2A regulates transcription of target genes by homo- or heterodimerization with cell specific bHLH proteins. In general, E2A promotes cell differentiation, acts as a negative regulator of cell proliferation in normal cells and cancer cell lines and is required for normal B-cell development. Given the diverse biological pathways regulated/influenced by E2A little is known about its expression in cancer. In this study we investigated the expression of E2A in prostate cancer. Unexpectedly, E2A immuno-histochemistry demonstrated increased E2A expression in prostate cancer as compared to normal prostate. Silencing of E2A in prostate cancer cells DU145 and PC3 led to a significant reduction in proliferation due to G1 arrest that was in part mediated by increased CDKN1A(p21) and decreased Id1, Id3 and c-myc. E2A silencing in prostate cancer cell lines also resulted in increased apoptosis due to increased mitochondrial permeability and caspase 3/7 activation. Moreover, silencing of E2A increased sensitivity to doxorubicin induced apoptosis. Based on our results, we propose that E2A could be an upstream regulator of Id1 and c-Myc which are highly expressed in prostate cancer. These results for the first time demonstrate that E2A could in fact acts as a tumor promoter at least in prostate cancer.

  6. Sustained pediatric antimicrobial stewardship program with consultation to infectious diseases reduced carbapenem resistance and infection-related mortality.

    Science.gov (United States)

    Horikoshi, Yuho; Suwa, Junichi; Higuchi, Hiroshi; Kaneko, Tetsuji; Furuichi, Mihoko; Aizawa, Yuta; Fukuoka, Kahoru; Okazaki, Kaoru; Ito, Kenta; Shoji, Takayo

    2017-11-01

    The impact of pediatric antimicrobial stewardship programs (ASP) on antimicrobial resistance (AMR) remains largely unknown. This study aimed to evaluate the AMR for carbapenem of Gram-negative bacilli (GNB) and carbapenem use with infectious diseases consultation after the implementation of an ASP. This quasi-experimental study was conducted at Tokyo Metropolitan Children's Medical Center in Japan. The pre- and post-intervention periods were April 2010 to September 2011 and October 2011 to March 2017, respectively. The pre-intervention phase consisted of consultations with the infectious diseases service alone. The ASP was implemented during the post-intervention phase. The carbapenem resistance rates of GNB were calculated. The correlation between carbapenem resistance rates and carbapenem day of therapy (DOT) was examined. The outcome metrics were compared by average length of hospitalization, all-cause mortality, and infection-related mortality. A positive correlation was observed between the carbapenem resistance rate in Pseudomonas aeruginosa and DOT (0.76, p=0.04). The carbapenem resistance rate in P. aeruginosa (pcarbapenem use and resistance in P. aeruginosa, leading to favorable outcomes in terms of length of hospitalization and infection-related mortality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. Insecticide resistance in Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) and Anopheles gambiae Giles (Diptera: Culicidae) could compromise the sustainability of malaria vector control strategies in West Africa.

    Science.gov (United States)

    Gnankiné, Olivier; Bassolé, Imael H N; Chandre, Fabrice; Glitho, Isabelle; Akogbeto, Martin; Dabiré, Roch K; Martin, Thibaud

    2013-10-01

    Insecticides from the organophosphate (OP) and pyrethroid (PY) chemical families, have respectively, been in use for 50 and 30 years in West Africa, mainly against agricultural pests, but also against vectors of human disease. The selection pressure, with practically the same molecules year after year (mainly on cotton), has caused insecticide resistance in pest populations such as Bemisia tabaci, vector of harmful phytoviruses on vegetables. The evolution toward insecticide resistance in malaria vectors such as Anopheles gambiae sensus lato (s.l.) is probably related to the current use of these insecticides in agriculture. Thus, successful pest and vector control in West Africa requires an investigation of insect susceptibility, in relation to the identification of species and sub species, such as molecular forms or biotypes. Identification of knock down resistance (kdr) and acetylcholinesterase gene (Ace1) mutations modifying insecticide targets in individual insects and measure of enzymes activity typically involved in insecticide metabolism (oxidase, esterase and glutathion-S-transferase) are indispensable in understanding the mechanisms of resistance. Insecticide resistance is a good example in which genotype-phenotype links have been made successfully. Insecticides used in agriculture continue to select new resistant populations of B. tabaci that could be from different biotype vectors of plant viruses. As well, the evolution of insecticide resistance in An. gambiae threatens the management of malaria vectors in West Africa. It raises the question of priority in the use of insecticides in health and/or agriculture, and more generally, the question of sustainability of crop protection and vector control strategies in the region. Here, we review the susceptibility tests, biochemical and molecular assays data for B. tabaci, a major pest in cotton and vegetable crops, and An. gambiae, main vector of malaria. The data reviewed was collected in Benin and Burkina

  8. SHP-1 activation inhibits vascular smooth muscle cell proliferation and intimal hyperplasia in a rodent model of insulin resistance and diabetes

    DEFF Research Database (Denmark)

    Qi, Weier; Li, Qian; Liew, Chong Wee

    2017-01-01

    . However, the role of SHP-1 in intimal hyperplasia and restenosis has not been clarified in insulin resistance and diabetes. METHODS: We used a femoral artery wire injury mouse model, rodent models with insulin resistance and diabetes, and patients with type 2 diabetes. Further, we modulated SHP-1...... expression using a transgenic mouse that overexpresses SHP-1 in VSMCs (Shp-1-Tg). SHP-1 agonists were also employed to study the molecular mechanisms underlying the regulation of SHP-1 by oxidised lipids. RESULTS: Mice fed a high-fat diet (HFD) exhibited increased femoral artery intimal hyperplasia...... and decreased arterial SHP-1 expression compared with mice fed a regular diet. Arterial SHP-1 expression was also decreased in Zucker fatty rats, Zucker diabetic fatty rats and in patients with type 2 diabetes. In primary cultured VSMCs, oxidised LDL suppressed SHP-1 expression by activating Mek-1 (also known...

  9. Aldo-keto reductase 1B10 promotes development of cisplatin resistance in gastrointestinal cancer cells through down-regulating peroxisome proliferator-activated receptor-γ-dependent mechanism.

    Science.gov (United States)

    Matsunaga, Toshiyuki; Suzuki, Ayaka; Kezuka, Chihiro; Okumura, Naoko; Iguchi, Kazuhiro; Inoue, Ikuo; Soda, Midori; Endo, Satoshi; El-Kabbani, Ossama; Hara, Akira; Ikari, Akira

    2016-08-25

    Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most effective chemotherapeutic drugs that are used for treatment of patients with gastrointestinal cancer cells, but its continuous administration often evokes the development of chemoresistance. In this study, we investigated alterations in antioxidant molecules and functions using a newly established CDDP-resistant variant of gastric cancer MKN45 cells, and found that aldo-keto reductase 1B10 (AKR1B10) is significantly up-regulated with acquisition of the CDDP resistance. In the nonresistant MKN45 cells, the sensitivity to cytotoxic effect of CDDP was decreased and increased by overexpression and silencing of AKR1B10, respectively. In addition, the AKR1B10 overexpression markedly suppressed accumulation and cytotoxicity of 4-hydroxy-2-nonenal that is produced during lipid peroxidation by CDDP treatment, suggesting that the enzyme acts as a crucial factor for facilitation of the CDDP resistance through inhibiting induction of oxidative stress by the drug. Transient exposure to CDDP and induction of the CDDP resistance decreased expression of peroxisome proliferator-activated receptor-γ (PPARγ) in MKN45 and colon cancer LoVo cells. Additionally, overexpression of PPARγ in the cells elevated the sensitivity to the CDDP toxicity, which was further augmented by concomitant treatment with a PPARγ ligand rosiglitazone. Intriguingly, overexpression of AKR1B10 in the cells resulted in a decrease in PPARγ expression, which was recovered by addition of an AKR1B10 inhibitor oleanolic acid, inferring that PPARγ is a downstream target of AKR1B10-dependent mechanism underlying the CDDP resistance. Combined treatment with the AKR1B10 inhibitor and PPARγ ligand elevated the CDDP sensitivity, which was almost the same level as that in the parental cells. These results suggest that combined treatment with the AKR1B10 inhibitor and PPARγ ligand is an effective adjuvant therapy for overcoming CDDP resistance of

  10. Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic Resistance

    Science.gov (United States)

    Boehme, Karen A.; Schleicher, Sabine B.; Rolauffs, Bernd

    2018-01-01

    Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC). PMID:29361725

  11. Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa

    Directory of Open Access Journals (Sweden)

    Z. Vergotine

    2014-01-01

    Full Text Available Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR, β-cells function (HOMA-B%, fasting insulin resistance index (FIRI, and the quantitative insulin-sensitivity check index (QUICKI were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (P=0.215. The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95. Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes.

  12. Sustainability of Water Reclamation: Long-Term Recharge with Reclaimed Wastewater Does Not Enhance Antibiotic Resistance in Sediment Bacteria

    Directory of Open Access Journals (Sweden)

    Jean E. McLain

    2014-03-01

    Full Text Available Wastewater reclamation for municipal irrigation is an increasingly attractive option for extending water supplies. However, public health concerns include the potential for development of antibiotic resistance (AR in environmental bacteria after exposure to residual pharmaceuticals in reclaimed water. Though scientific studies have reported high levels of AR in soils irrigated with wastewater, these works often fail to address the soil resistome, or the natural occurrence of AR. This study compared AR patterns in sediment Enterococcus isolated from water storage basins containing either reclaimed water or groundwater in central Arizona. Resistance to 16 antibiotics was quantified in isolates to a depth of 30 cm. Results reveal high levels of resistance to certain antibiotics, including lincomycin, ciprofloxacin, and erythromycin, exists in sediments regardless of the water source (groundwater, reclaimed water, and higher AR was not detectable in reclaimed water sediments. Furthermore, multiple-antibiotic-resistance (MAR was substantially reduced in isolates from reclaimed water sediments, compared to freshwater sediment isolates. Comparing the development of AR in sediment bacteria at these two sites will increase awareness of the environmental and public health impacts of using reclaimed water for irrigation of municipal areas, and illustrates the necessity for control sites in studies examining AR development in environmental microbiota.

  13. Chronic exposure to triclosan sustains microbial community shifts and alters antibiotic resistance gene levels in anaerobic digesters.

    Science.gov (United States)

    Carey, Daniel E; Zitomer, Daniel H; Kappell, Anthony D; Choi, Melinda J; Hristova, Krassimira R; McNamara, Patrick J

    2016-08-10

    Triclosan, an antimicrobial chemical found in consumer personal care products, has been shown to stimulate antibiotic resistance in pathogenic bacteria. Although many studies focus on antibiotic resistance pertinent to medical scenarios, resistance developed in natural and engineered environments is less studied and has become an emerging concern for human health. In this study, the impacts of chronic triclosan (TCS) exposure on antibiotic resistance genes (ARGs) and microbial community structure were assessed in lab-scale anaerobic digesters. TCS concentrations from below detection to 2500 mg kg(-1) dry solids were amended into anaerobic digesters over 110 days and acclimated for >3 solid retention time values. Four steady state TCS concentrations were chosen (30-2500 mg kg(-1)). Relative abundance of mexB, a gene coding for a component of a multidrug efflux pump, was significantly higher in all TCS-amended digesters (30 mg kg(-1) or higher) relative to the control. TCS selected for bacteria carrying tet(L) and against those carrying erm(F) at concentrations which inhibited digester function; the pH decrease associated with digester failure was suspected to cause this selection. Little to no impact of TCS was observed on intI1 relative abundance. Microbial communities were also surveyed by high-throughput 16S rRNA gene sequencing. Compared to the control digesters, significant shifts in community structure towards clades containing commensal and pathogenic bacteria were observed in digesters containing TCS. Based on these results, TCS should be included in studies and risk assessments that attempt to elucidate relationships between chemical stressors (e.g. antibiotics), antibiotic resistance genes, and public health.

  14. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... how antimicrobial resistance both emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will result in the development of resistant strains of bacteria, complicating clinician's efforts to select the appropriate antimicrobial ...

  15. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xiu Juan Li

    2017-12-01

    Full Text Available Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246 as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2, indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

  16. Strengthening the non proliferation regime: French views

    International Nuclear Information System (INIS)

    Delaune, P.

    2013-01-01

    3 main issues can be identified in the French policy concerning the backing of non proliferation: 1) responding resolutely to proliferation crises, 2) reinforcing substantive efforts to prevent and impede proliferation, and 3) strengthening the non-proliferation regime. The first issue is very important because combating proliferation is vital to the security of all. Concerning the second issue, France attaches particular importance to strengthening specific measures to prevent and check proliferation. Let me mention a few proposals that we put forward: exports need to be controlled more effectively, proliferation activities have to be criminalized, or the development of proliferation-resistant technologies should be supported. Concerning the third issue it means the strengthening of the non-proliferation regime, France proposes several means: -) aiming at the universalization of the additional protocol; -) ensuring that the Agency continues to have sufficient human, financial and technical resources to fulfill its verification mission effectively; -) encouraging the IAEA to make full use of the authority available to it; -) enhancing the use of information relevant to the delivery of the IAEA mandate; and -) sharing more accurate information concerning the breaches of commitments that happen. The paper is followed by the slides of the presentation. (A.C.)

  17. The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts.

    Directory of Open Access Journals (Sweden)

    Jelena Markovic

    2009-07-01

    Full Text Available Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate.We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM and buthionine sulfoximine (BSO, and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation.Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle.

  18. Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer.

    Science.gov (United States)

    Li, Xiu Juan; Ren, Zhao Jun; Tang, Jin Hai; Yu, Qiao

    2017-01-01

    Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. Energy efficiency and proliferation assessment factors

    International Nuclear Information System (INIS)

    1979-02-01

    The objective of INFCE is to evaluate the nuclear fuel cycles from the point of view of their ability to satisfy the worldwide nuclear energy needs, while minimizing the proliferation risks. Accordingly, the different working groups have to take into consideration as well the energy-efficiency and the proliferation-resistance of these nuclear fuel cycles. The present working paper is aimed at suggesting the main assessment factors which should be taken into consideration

  20. The role of accelerator-based systems for optimal elimination of plutonium to minimize global proliferation risks

    International Nuclear Information System (INIS)

    Liebert, W.; Glaser, A.; Pistner, C.

    1997-01-01

    The new proliferation dangers associated with plutonium coming out of the dismantlement of nuclear warheads and the fact that nearly all mixtures of plutonium isotopes are weapon-usable highlight the need for a sustainable disposition option. This paper gives an overview on existing military as well as civilian plutonium stocks worldwide and estimates their future development. An assessment of pros and cons of disposition options discussed so far shows that only the capability of an accelerator-based system to eliminate the plutonium virtually completely makes it attractive from the non-proliferator's point of view. We propose a set of criteria to guide the development of an appropriate system. Special attention is directed on overall proliferation resistance and safety aspects without being compromised by power generation. 17 refs., 1 fig., 1 tab

  1. The threat of proliferation

    International Nuclear Information System (INIS)

    Palme, Olof.

    1986-01-01

    The paper on the threat of proliferation, is a keynote speech delivered to the Colloquium on Nuclear War, Nuclear Proliferation and their Consequences, Geneva, 1985. Topics discussed in the address include: nuclear weapons, nuclear war, terrorists, Non-Proliferation Treaty, nuclear disarmament, and leadership in world affairs. (UK)

  2. One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus.

    Science.gov (United States)

    van Asseldonk, Edwin J P; van Poppel, Pleun C M; Ballak, Dov B; Stienstra, Rinke; Netea, Mihai G; Tack, Cees J

    2015-10-01

    Inflammation associated with obesity is involved in the development of insulin resistance. We hypothesized that anti-inflammatory treatment with the Interleukin-1 receptor antagonist anakinra would improve insulin sensitivity. In an open label proof-of-concept study, we included overweight patients diagnosed with type 1 diabetes with an HbA1c level over 7.5%. Selecting insulin resistant patients with longstanding type 1 diabetes allowed us to study the effects of anakinra on insulin sensitivity. Patients were treated with 100mg anakinra daily for one week. Insulin sensitivity, insulin need and blood glucose profiles were measured before, after one week and after four weeks of follow-up. Fourteen patients completed the study. One week of anakinra treatment led to an improvement of insulin sensitivity, an effect that was sustained for four weeks. Similarly, glucose profiles, HbA1c levels and insulin needs improved. In conclusion, one week of treatment with anakinra improves insulin sensitivity in patients with type 1 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Future non-proliferation challenges

    International Nuclear Information System (INIS)

    Yelchenko, Volodymyr

    2008-01-01

    activities and illicit trafficking of nuclear material, equipment and technology. The strengthening of the physical protection of nuclear materials and facilities as an element of non-proliferation regime was highlighted. The proliferation risks associated with the growing global energy demand were also mentioned. In this regard, attention was drawn to the significance of developing proliferation resistant nuclear technologies, including through the international project on Innovative Nuclear Reactors and Fuel Cycles (INPRO). It is important to mention the discussion concerning the promotion of multilateralism in the nuclear fuel cycle and the supply of nuclear fuel, which was considered as a significant contribution to confidence-building in the field of non proliferation, to peaceful uses of nuclear energy and to the overall strength of the non-proliferation regime. The ongoing discussions in IAEA on fuel supply assurances mechanism were welcomed. The NPT relative success in slowing proliferation has been attributed to the combination of the political commitment by most states to the objective of non-proliferation, and a technical mechanism - IAEA safeguards - for verifying that this commitment is being honoured. Indeed, the IAEA will remain an indispensable part of the multilateral nuclear non proliferation regime and global security system and its role should be significantly strengthened. He hopes that the meeting will help to identify the ways of enhancing the important work of IAEA

  4. Proliferation Vulnerability Red Team report

    Energy Technology Data Exchange (ETDEWEB)

    Hinton, J.P.; Barnard, R.W.; Bennett, D.E. [and others

    1996-10-01

    This report is the product of a four-month independent technical assessment of potential proliferation vulnerabilities associated with the plutonium disposition alternatives currently under review by DOE/MD. The scope of this MD-chartered/Sandia-led study was limited to technical considerations that could reduce proliferation resistance during various stages of the disposition processes below the Stored Weapon/Spent Fuel standards. Both overt and covert threats from host nation and unauthorized parties were considered. The results of this study will be integrated with complementary work by others into an overall Nonproliferation and Arms Control Assessment in support of a Secretarial Record of Decision later this year for disposition of surplus U.S. weapons plutonium.

  5. Understanding plant defence responses against herbivore attacks: an essential first step towards the development of sustainable resistance against pests.

    Science.gov (United States)

    Santamaria, M Estrella; Martínez, Manuel; Cambra, Inés; Grbic, Vojislava; Diaz, Isabel

    2013-08-01

    Plant-herbivore relationships are complex interactions encompassing elaborate networks of molecules, signals and strategies used to overcome defences developed by each other. Herbivores use multiple feeding strategies to obtain nutrients from host plants. In turn, plants respond by triggering defence mechanisms to inhibit, block or modify the metabolism of the pest. As part of these defences, herbivore-challenged plants emit volatiles to attract natural enemies and warn neighbouring plants of the imminent threat. In response, herbivores develop a variety of strategies to suppress plant-induced protection. Our understanding of the plant-herbivore interphase is limited, although recent molecular approaches have revealed the participation of a battery of genes, proteins and volatile metabolites in attack-defence processes. This review describes the intricate and dynamic defence systems governing plant-herbivore interactions by examining the diverse strategies plants employ to deny phytophagous arthropods the ability to breach newly developed mechanisms of plant resistance. A cornerstone of this understanding is the use of transgenic tools to unravel the complex networks that control these interactions.

  6. Proliferation: myth or reality?

    International Nuclear Information System (INIS)

    2005-01-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  7. Towards proliferation-resistant thorium fuels

    International Nuclear Information System (INIS)

    Alhaj, M. Yousif; Mohamed, Nader M.A.; Badawi, Alya; Abou-Gabal, Hanaa H.

    2017-01-01

    Thorium-plutonium mixture is proposed as alternative nuclear reactor fuel to incinerate the increasing stockpile plutonium. However, this fuel will produce an amount of uranium with about 90% 233U at applicable discharge burnups (60GWD/MTU). This research focuses on proposing an optimum non proliferative thorium fuel, by adding a small amount of 238U to reduce the attractiveness of the resultant uranium. Three types of additive which contain 238U were used: 4.98% enriched, natural and depleted uranium. We found that introducing uranium to the fresh thorium-plutonium fuel reduces its performance even if the uranium was enriched up to 5%. While uranium admixtures reduce the quality of the reprocessed uranium, it also increases the quality of the plutonium. However, this increase is very low compared to the reduced quality of uranium. We also found that using uranium as admixture for thorium-plutonium mixed fuel increases the critical mass of the extracted uranium by a factor of two when using only 1% admixture of uranium. The higher the percentage of uranium admixture the higher the critical mass of the reprocessed one.

  8. Sustained effect of resistance training on blood pressure and hand grip strength following a detraining period in elderly hypertensive women: a pilot study

    Directory of Open Access Journals (Sweden)

    Nascimento D da C

    2014-01-01

    effects were sustained after 14 weeks of detraining. Conclusion: Resistance training may be a valuable method to improve muscular strength and blood pressure in elderly people with benefits being maintained up to 14 weeks following training cessation. Keywords: aging, resistance training, hypertension, detraining, elderly

  9. Director's series on proliferation

    International Nuclear Information System (INIS)

    Bailey, K.C.; Price, M.E.

    1995-01-01

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author's. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia's Nuclear Legacy

  10. Proliferation Networks and Financing

    International Nuclear Information System (INIS)

    Gruselle, Bruno

    2007-01-01

    The objective of this study is to propose practical solutions aimed at completing and strengthening the existing arrangement for the control of nuclear proliferation through a control of financial as well as material or immaterial flows. In a first part, the author proposes a systemic analysis of networks of suppliers and demanders. He notably evokes the Khan's network and the Iraqi acquisition network during the 1993-2001 period. He also proposes a modelling of proliferation networks (supplier networks and acquisition networks) and of their interactions. In a second part, the author examines possible means and policies aimed at neutralising proliferation networks: organisation, adaptation and improvement of intelligence tools in front of proliferation networks, and means, limitations and perspectives of network neutralisation. He also briefly addresses the possibility of military action to contain proliferation flows

  11. Proper Tools Helping Sustainability in Logistics Practice

    NARCIS (Netherlands)

    Alrik Stelling; Nico Lamers; Gerard Vos; Reinder Pieters; Stef Weijers; Erik Koekebakker

    2009-01-01

    Proliferation on sustainability is a must, for quite a lot of companies. Logisticians could use models in attaining sustainability, or at least in understanding its potentials. A sustainable business plan must be based on a clear vision and must be underpinned thoroughly, in order to get the board

  12. Utility of Social Modeling for Proliferation Assessment - Preliminary Findings

    International Nuclear Information System (INIS)

    Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J.; Thompson, Sandra E.

    2009-01-01

    Often the methodologies for assessing proliferation risk are focused around the inherent vulnerability of nuclear energy systems and associated safeguards. For example an accepted approach involves ways to measure the intrinsic and extrinsic barriers to potential proliferation. This paper describes preliminary investigation into non-traditional use of social and cultural information to improve proliferation assessment and advance the approach to assessing nuclear material diversion. Proliferation resistance assessment, safeguard assessments and related studies typically create technical information about the vulnerability of a nuclear energy system to diversion of nuclear material. The purpose of this research project is to find ways to integrate social information with technical information by explicitly considering the role of culture, groups and/or individuals to factors that impact the possibility of proliferation. When final, this work is expected to describe and demonstrate the utility of social science modeling in proliferation and proliferation risk assessments.

  13. Non-proliferation

    International Nuclear Information System (INIS)

    Manley, I.T.

    1981-01-01

    Proliferation is a problem that can only be solved when the political problems which lead countries to contemplate, the possession of nuclear weapons are solved; in the meantime it can only be managed. Non-proliferation policy has to deal both with the political and the technical aspects of proliferation. It must seek to buy time by addressing the reasons why nations feel the political need to construct nuclear weapons, as well as delaying the moment when such nations feel capable of doing so. The subject is examined and proposals made. (author)

  14. Getting serious about proliferation

    International Nuclear Information System (INIS)

    Leventhal, P.

    1984-01-01

    The US needs to give a higher priority to nuclear non-proliferation, but Reagan's policies assume that proliferation is inevitable and that it is more important to be a reliable supplier than to cause trade frictions by trading only with those nations which sign the non-proliferation treaty (NPT). This undercuts US leadership and the intent of the agreement. Several bills now before Congress could help to restore US leadership by tightening export restrictions and the use of plutonium from the US

  15. The US proliferation security initiative (PSI)

    International Nuclear Information System (INIS)

    Gregoire, B.

    2004-01-01

    The proliferation security initiative (PSI), launched by President Bush on May 31, 2003, aims at intercepting any transfer of mass destruction weapons, of their vectors and related equipments, towards or coming from countries or organizations suspected to have a proliferation activity. This initiative, which involves coercive means to fight against proliferation, raises international lawfulness and legal questions, the answers of which are today under construction. This article analyzes the place of the European Union in the PSI, the action means (optimization of existing means, cooperation between intelligence and interception services), and the PSI stakes (lawfulness with respect to the international law, bilateral agreements, draft boarding agreement, sustain of the United Nations, widening of the partnership and of the field of action). (J.S.)

  16. Acellular dermal matrix loading with bFGF achieves similar acceleration of bone regeneration to BMP-2 via differential effects on recruitment, proliferation and sustained osteodifferentiation of mesenchymal stem cells

    International Nuclear Information System (INIS)

    Du, Mi; Zhu, Ting; Duan, Xiaoqi; Ge, Shaohua; Li, Ning; Sun, Qinfeng; Yang, Pishan

    2017-01-01

    New generation of barrier membranes has been developed, which not only act as barriers but also as delivery devices to release specific growth factors. This study observed biological behaviors of bone morrow mesenchymal stem cells (BMMSCs) pretreated by bFGF or BMP-2 in vitro and evaluated differential bone regeneration process induced by bFGF and BMP-2 loaded acellular dermal matrix (ADM) membrane using critical-size rat calvarial defect model in vivo. The results showed that the proliferation capability of BMMSCs pretreated by bFGF was stronger than that by BMP-2, while there was temporally differential effect of bFGF and BMP-2 pretreatment on MSC osteogenic differentiation potentials. During healing process of rat calvarial defects, 2-fold more CD34 −/CD90 + MSCs in group of bFGF-ADM was observed than in any other treatment group at 2 weeks. However, there were similar amount of new bone formation and expression of osteopotin in newly-formed bone tissue in groups of bFGF- and BMP-2-ADM at 8 weeks, which were more than those in ADM alone and blank control. Taken together, bFGF-ADM guided similar bone regeneration to BMP-2 through more efficient recruitment of MSCs, and moreover, BMMSCs pretreated by bFGF showed stronger proliferation at 1–5 days and osteogenic differentiation potentials at 14 days compared with BMP-2 pretreatment. - Highlights: • An improved barrier membrane used in the field of bone tissue engineering was proposed, which is acellular dermal matrix (ADM) loaded with growth factors. • It is generally agreed that BMP-2 and -7 provide the greatest bone regeneration potentials, however, we found that ADM loading with bFGF could guide similar bone regeneration to BMP-2. • Compared with BMP-2, bFGF could more effectively recruit MSCs and moreover, BMMSCs pretreated by bFGF showed out stronger proliferation at 1-5 days and osteogenic differentiation potentials at 14 days.

  17. Strengthening the nuclear non-proliferation regime

    International Nuclear Information System (INIS)

    Carlson, J.

    2003-01-01

    Although the nuclear non-proliferation regime has enjoyed considerable success, today the regime has never been under greater threat. Three states have challenged the objectives of the NPT, and there is a technology challenge - the spread of centrifuge enrichment technology and know-how. A major issue confronting the international community is, how to deal with a determined proliferator? Despite this gloomy scenario, however, the non-proliferation regime has considerable strengths - many of which can be developed further. The regime comprises complex interacting and mutually reinforcing elements. At its centre is the NPT - with IAEA safeguards as the Treaty's verification mechanism. Important complementary elements include: restraint in the supply and the acquisition of sensitive technologies; multilateral regimes such as the CTBT and proposed FMCT; various regional and bilateral regimes; the range of security and arms control arrangements outside the nuclear area (including other WMD regimes); and the development of proliferation-resistant technologies. Especially important are political incentives and sanctions in support of non-proliferation objectives. This paper outlines some of the key issues facing the non-proliferation regime

  18. Supporting non proliferation and global security efforts

    International Nuclear Information System (INIS)

    Pochon, E.

    2013-01-01

    CEA contributes as a major actor of France's action against nuclear proliferation and to the strengthening of nuclear security at national level as European and International levels, in particular through the support of the IAEA activities in nuclear non proliferation with the French Support Programme for the IAEA safeguards system and security with the contribution to the IAEA Nuclear Security Plan and cooperation projects with the European Commission. The CEA is a French government funded technological research organization, organized around 5 branches: Nuclear Energy, Technological Researches, Defence (DAM), Material Sciences and Life Sciences. Within the scope of its activities, CEA covers most of the research areas and techniques in nuclear non-proliferation and security. The CEA is also the advisor of the French Government on nuclear policy. Treaty monitoring and the development and implementation of non proliferation and global security programs is an important mission of DAM which rely on nuclear weapons manufacture and past testing experience. The programmes on non proliferation and global security carried out to fulfil DAM's mission cover the following areas: development of monitoring and detection methods and equipments, country profiles and nuclear stockpiles assessment, arms control instruments, proliferation resistance of nuclear fuel cycle, monitoring of nuclear tests, operation and maintenance of national detection capabilities and contribution to CTBT verification systems. (A.C.)

  19. Nuclear proliferation and terrorism

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    This section of the book, Part III, has two chapters (9 and 10). Chapter 9, Nuclear Power and Proliferation of Nuclear Weapons, is disucssed under these subjects: nuclear nonproliferation: origins and status; requirements for nuclear weapons manufacture; current nuclear programs and proliferation capabilities; encouraging decisions to forego weapons; arms control; safeguards; attitudes and expectations. Chapter 10, Nuclear Terrorism, discusses these areas: theft of nuclear materials; attacks on nuclear reactors; responding to nuclear terrorism; security and civil liberties

  20. Gemcitabine resistance in breast cancer cells regulated by PI3K/AKT-mediated cellular proliferation exerts negative feedback via the MEK/MAPK and mTOR pathways

    Directory of Open Access Journals (Sweden)

    Yang XL

    2014-06-01

    ability of 231/Gem cells. Western blot analysis showed that treatment with a PI3K/AKT inhibitor decreased the expression levels of p-AKT, p-MEK, p-mTOR, and p-P70S6K; however, treatments with either MEK/MAPK or mTOR inhibitor significantly increased p-AKT expression. Thus, our data suggest that gemcitabine resistance in breast cancer cells is mainly mediated by activation of the PI3K/AKT signaling pathway. This occurs through elevated expression of p-AKT protein to promote cell proliferation and is negatively regulated by the MEK/MAPK and mTOR pathways. Keywords: chemoresistance, gemcitabine, breast cancer

  1. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... search Popular ... produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will ...

  2. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... proliferates among bacteria. Over time, the use of antimicrobial drugs will result in the development of resistant strains ... bacteria, complicating clinician's efforts to select the appropriate ... and human medicine to preserve the effectiveness of these drugs. One ...

  3. Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

    NARCIS (Netherlands)

    Korsheninnikova, E.; van der Zon, G. C. M.; Voshol, P. J.; Janssen, G. M.; Havekes, L. M.; Grefhorst, A.; Kuipers, F.; Reijngoud, D.-J.; Romijn, J. A.; Ouwens, D. M.; Maassen, J. A.

    2006-01-01

    Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Chronic hepatic steatosis and hepatic insulin resistance

  4. Grassland Sustainability

    Science.gov (United States)

    Deborah U. Potter; Paulette L. Ford

    2004-01-01

    In this chapter we discuss grassland sustainability in the Southwest, grassland management for sustainability, national and local criteria and indicators of sustainable grassland ecosystems, and monitoring for sustainability at various scales. Ecological sustainability is defined as: [T]he maintenance or restoration of the composition, structure, and processes of...

  5. Nuclear dilemma: power, proliferation, and development

    International Nuclear Information System (INIS)

    Miller, M.

    1979-01-01

    Debate over President Carter's nuclear energy policy centers on how to develop nuclear power for civilian use and prevent the proliferation of nuclear materials for weapons. Both supporters and opponents of nuclear energy have been critical of Carter's policies because each side fails to see the linkage between the two concerns as codified in the 1978 Non-Proliferation Act. The author uses a dialogue format to illustrate the arguments for resisting proliferation and recognizing nuclear energy as an appropriate technology. The consequences of a nuclear moratorium are explored along with implications for foreign policy. U.S. leadership in developing energy technologies that can meet a broad range of appropriate applications, combined with leadership in building appropriate political frameworks, is needed if nuclear energy is to make a positive contribution toward world peace and acceptable living standards. 8 references

  6. Nuclear non-proliferation

    International Nuclear Information System (INIS)

    Anon.

    1984-01-01

    DOE's nuclear non-proliferation responsibilities are defined by the provisions of the Atomic Energy Act of 1954, as amended, and of the Nuclear Non-Proliferation Act of 1978 (NNPA). The Department's major responsibilities in this area are to: (1) provide technical assistance to the Department of State in negotiating agreements for civil cooperation in the peaceful uses of nuclear energy with other countries and international organizations; (2) join with other agencies to reach executive branch judgments with respect to the issuance of export licenses by the Nuclear Regulatory Commission; (3) be responsible for processing subsequent arrangements with other agencies as required by the Nuclear Non-Proliferation Act; (4) control the distribution of special nuclear materials, components, equipment, and nuclear technology exports; (5) participate in bilateral and multilateral cooperation with foreign governments and organizations to promote the peaceful uses of nuclear energy; and (6) act as a primary technical resource with respect to US participation in the International Atomic Energy Agency

  7. Dynamics of nuclear proliferation

    International Nuclear Information System (INIS)

    Meyer, S.M.

    1984-01-01

    This book looks beyond policy disputes to make a systematic examination of the assumptions and contending hypotheses that constitute contemporary thinking on nuclear proliferation. Rather than determine who is right or wrong, the intent is to develop a better picture by using the various schools of thought as analytic windows. A better understanding of how the process operates should offer better guidance for predicting future nuclear proliferation and, ultimately, for controlling it. Separate chapters deal with the contending views, the technological and motivational bases of nuclear proliferation, the presence of a technological imperative, testing the motivational hypothesis, the dynamics of the process, and forecasting. Four appendices present historical decisions, the technical model, cost-estimating procedures, and procedures for estimating nuclear propensities. 288 references, 17 figures, 26 tables

  8. Limiting Future Proliferation and Security Risks

    International Nuclear Information System (INIS)

    Bari, R.

    2011-01-01

    A major new technical tool for evaluation of proliferation and security risks has emerged over the past decade as part the activities of the Generation IV International Forum. The tool has been developed by a consensus group from participating countries and organizations and is termed the Proliferation Resistance and Physical Protection (PR and PP) Evaluation Methodology. The methodology defines a set of challenges, analyzes system response to these challenges, and assesses outcomes. The challenges are the threats posed by potential actors (proliferant states or sub-national adversaries). It is of paramount importance in an evaluation to establish the objectives, capabilities, resources, and strategies of the adversary as well as the design and protection contexts. Technical and institutional characteristics are both used to evaluate the response of the system and to determine its resistance against proliferation threats and robustness against sabotage and terrorism threats. The outcomes of the system response are expressed in terms of a set of measures, which thereby define the PR and PP characteristics of the system. This paper summarizes results of applications of the methodology to nuclear energy systems including reprocessing facilities and large and small modular reactors. The use of the methodology in the design phase a facility will be discussed as it applies to future safeguards concepts.

  9. Cell Proliferation in Neuroblastoma

    Science.gov (United States)

    Stafman, Laura L.; Beierle, Elizabeth A.

    2016-01-01

    Neuroblastoma, the most common extracranial solid tumor of childhood, continues to carry a dismal prognosis for children diagnosed with advanced stage or relapsed disease. This review focuses upon factors responsible for cell proliferation in neuroblastoma including transcription factors, kinases, and regulators of the cell cycle. Novel therapeutic strategies directed toward these targets in neuroblastoma are discussed. PMID:26771642

  10. Controlling nuclear proliferation

    International Nuclear Information System (INIS)

    Sweet, W.

    1981-01-01

    Nuclear non-proliferation policy depends on the 1968 Non-Proliferation Treaty, in which countries promise not to acquire nuclear weapons in exchange for open access to peaceful nuclear technology, and a system of international safeguards that are imposed on exported nuclear equipment and facilities operated by parties to the treaty. Critics have feared all along that non-nuclear countries might circumvent or exploit the system to obtain nuclear weapons and that the Atoms for Peace plan would spread the very technology it sought to control. The nuclear weapons states would like everyone else to believe that atomic bombs are undesirable, but they continue to rely on the bombs for their own defense. Israel's raid on Iraq's nuclear reactor focused world attention on the proliferation problem and helped to broaden and sterengthen its prospects. It also highlighted the weakness that there are no effective sanctions against violators. Until the international community can ageee on enforcement measures powerful enough to prevent nuclear proliferation, individual countries may be tempted to follow Israel's example, 19 references

  11. Sustainable Food & Sustainable Economics

    OpenAIRE

    Alvarez, Mavis Dora

    2012-01-01

    Cuba today is immersed in a very intense process of perfecting its agricultural production structures with the goal of making them more efficient and sustainable in their economic administration and in their social and environmental management. Agricultural cooperatives in Cuba have the responsibility of producing on 73% of the country's farmland. Their contributions are decisive to developing agricultural production and to ensuring more and better food for the population, in addition to redu...

  12. Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

    NARCIS (Netherlands)

    Korsheninnikova, E.; van der Zon, G. C. M.; Voshol, P. J.; Janssen, G. M.; Havekes, L. M.; Grefhorst, A.; Kuipers, F.; Reijngoud, D. -J.; Romijn, J. A.; Ouwens, D. M.; Maassen, J. A.

    2006-01-01

    Aims/hypothesis Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods Chronic hepatic

  13. INPRO Methodology for Sustainability Assessment of Nuclear Energy Systems: Environmental Impact of Stressors. INPRO Manual

    International Nuclear Information System (INIS)

    2016-01-01

    This publication provides guidance on assessing of sustainability of a nuclear energy system (NES) in the area of environmental impact of stressors. The INPRO methodology is a comprehensive tool for the assessment of sustainability of an NES. Basic principles, user requirements and criteria have been defined in different areas of INPRO methodology. These include economics, infrastructure, waste management, proliferation resistance, environmental impact of stressors, environmental impact from depletion of resources, and safety of nuclear reactors and fuel cycle facilities. The ultimate goal of the application of the INPRO methodology is to check whether the assessed NES fulfils all the criteria, and hence the user requirements and basic principles, and therefore presents a system for a Member State that is sustainable in the long term

  14. Nuclear non-proliferation

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    This patent describes the treaty on the non-proliferation of nuclear weapons which is the corner-stone of an international non-proliferation regime which has grown to embrace the overwhelming majority of countries in the world in the period since the Treaty. The other elements of the regime include, first of all, the safeguards system of IAEA-which operates to prevent the diversion of nuclear materials to military or other prohibited activities and must be accepted by all non-nuclear-weapon parties to the Treaty and, secondly, the Antarctic Treaty, the Treaty for the Prohibition of Nuclear Weapons in Latin America (Treaty of Tlatelolco) and the south Pacific Nuclear Free zone Treaty (Treaty of Rarotonga)-which serve to extend the regime geographically. The last two Treaties require safeguards agreements with IAEA. In addition, the Treaty of Tlatelolco contains provisions establishing the agency for the Prohibition of Nuclear Weapons in Latin America and the Caribbean to ensure compliance

  15. Proliferation in cycle

    Energy Technology Data Exchange (ETDEWEB)

    Piao Yunsong [College of Physical Sciences, Graduate School of Chinese Academy of Sciences, Beijing 100049 (China)], E-mail: yspiao@gucas.ac.cn

    2009-06-15

    In the contracting phase with w{approx_equal}0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w{approx_equal}0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

  16. Proliferation in cycle

    International Nuclear Information System (INIS)

    Piao Yunsong

    2009-01-01

    In the contracting phase with w≅0, the scale invariant spectrum of curvature perturbation is given by the increasing mode of metric perturbation. In this Letter, it is found that if the contracting phase with w≅0 is included in each cycle of a cycle universe, since the metric perturbation is amplified on super horizon scale cycle by cycle, after each cycle the universe will be inevitably separated into many parts independent of one another, each of which corresponds to a new universe and evolves up to next cycle, and then is separated again. In this sense, a cyclic multiverse scenario is actually presented, in which the universe proliferates cycle by cycle. We estimate the number of new universes proliferated in each cycle, and discuss the implications of this result.

  17. Global proliferation concerns

    International Nuclear Information System (INIS)

    Simpkins, R.

    1978-01-01

    The Non-Proliferation Treaty and the IAGA Safeguards System are discussed. President Carter's program to defer commercial reprocessing and recycle, to restructure the breeder program, to develop alternative fuel cycles, to increase US uranium enrichment capability, to provide fuel assurance for consumer nations, to continue the embargo of sensitive technology and equipment and to develop the International Nuclear Fuel Cycle Evaluation Program is outlined

  18. Impact of Salinomycin on human cholangiocarcinoma: induction of apoptosis and impairment of tumor cell proliferation in vitro

    Directory of Open Access Journals (Sweden)

    Lieke Thorsten

    2012-10-01

    Full Text Available Abstract Background Cholangiocarcinoma (CC is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. Methods To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry. Results By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration. Conclusion In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.

  19. Proliferation after the Iraq war

    International Nuclear Information System (INIS)

    Daguzan, J.F.

    2004-09-01

    This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

  20. Can we predict nuclear proliferation

    International Nuclear Information System (INIS)

    Tertrais, Bruno

    2011-01-01

    The author aims at improving nuclear proliferation prediction capacities, i.e. the capacities to identify countries susceptible to acquire nuclear weapons, to interpret sensitive activities, and to assess nuclear program modalities. He first proposes a retrospective assessment of counter-proliferation actions since 1945. Then, based on academic studies, he analyzes what causes and motivates proliferation, with notably the possibility of existence of a chain phenomenon (mechanisms driving from one program to another). He makes recommendations for a global approach to proliferation prediction, and proposes proliferation indices and indicators

  1. Perspective of nuclear fuel cycle for sustainable nuclear energy

    International Nuclear Information System (INIS)

    Fukuda, K.; Bonne, A.; Kagramanian, V.

    2001-01-01

    Nuclear power, on a life-cycle basis, emits about the same level of carbon per unit of electricity generated as wind and solar power. Long-term energy demand and supply analysis projects that global nuclear capacities will expand substantially, i.e. from 350 GW today to more than 1,500 GW by 2050. Uranium supply, spent fuel and waste management, and a non-proliferation nuclear fuel cycle are essential factors for sustainable nuclear power growth. An analysis of the uranium supply up to 2050 indicates that there is no real shortage of potential uranium available if based on the IIASA/WEC scenario on medium nuclear energy growth, although its market price may become more volatile. With regard to spent fuel and waste management, the short term prediction foresees that the amount of spent fuel will increase from the present 145,000 tHM to more than 260,000 tHM in 2015. The IPCC scenarios predicted that the spent fuel quantities accumulated by 2050 will vary between 525 000 tHM and 3 210 000 tHM. Even according to the lowest scenario, it is estimated that spent fuel quantity in 2050 will be double the amount accumulated by 2015. Thus, waste minimization in the nuclear fuel cycle is a central tenet of sustainability. The proliferation risk focusing on separated plutonium and resistant technologies is reviewed. Finally, the IAEA Project INPRO is briefly introduced. (author)

  2. Sustainable Marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    In this article, three different conceptions of sustainable marketing are discussed and compared. These different conceptions are referred to as social, green, and critical sustainable marketing. Social sustainable marketing follows the logic of demand-driven marketing management and places the

  3. HTGR strategy for reduced proliferation potential

    International Nuclear Information System (INIS)

    Stewart, H.B.; Dahlberg, R.C.

    1978-01-01

    The HTGR stratregy for reduced proliferation potential is one aspect of a potential broader nuclear strategy aimed primarily toward a transition nuclear period between today's uranium-consumption reactors and the long-range balanced system of breeder and advanced near-breeder reactors. In particular, the normal commerce of U-233 could be made acceptable by: (a) dependence on the gamma radiation from U-232 daughter products, (b) enhancement of that radioactivity by incomplete fission-product decontamination of the bred-fuel, or (c) denaturing of the U-233 with U-238. These approaches would, of course, supplement institutional initiatives to improve proliferation resistance such as the collocation of facilities and the establishment of secure energy centers. 6 refs

  4. Non-proliferation

    International Nuclear Information System (INIS)

    Deiseroth, D.; Gustafsson, S.

    1993-01-01

    The issue of Nuclear Non Proliferation has been moved to a leading place on the contemporary international security agenda. What about the situation of nuclear weapons and nuclear technology in Russia, Kazakhstan, Ukraine and Belorussia? Why did the IAEA-inspectors totally failed to discover any sign of Iraq's clandestine nuclear-weapon programme before the Gulf War? Do the NATO and their nuclear power states violate Art. VI of the Non-Proliferation-Treaty (NPT), because they are - despite the end of the cold war - not willing to renounce of the ''option of the first use of nuclear weapons''? Does the NPT establish a form of nuclear apartheid? What will be the situation if the NPT-Extension-Conference in 1995 will be unable to obtain a majority of the parties for any one extension proposal? Do we need a new international nuclear control agency with severe powers, a sort of nuclear Interpol? The Colloquium ''Saving NPT and abolishing Nuclear Weapons'', held in Stockholm in September 1992, organized by the Swedish and the German Sections of IALANA, tried to analyse some of the raised issues. (orig.) [de

  5. Non Proliferation of Nuclear

    International Nuclear Information System (INIS)

    Bambang S Irawan

    2004-01-01

    Non-Proliferation Treaty of Nuclear Weapons is the international community's efforts to maintain the security of the world, in order to prevent the spread of nuclear technology and the use of nuclear weapons, promoting cooperation for the use of nuclear peaceful purposes, build mutual trust (Confidence Building Measures) as well as to achieve the ultimate goal of disarmament overall (General and Complete Disarmament). Addressing the post-WTC tragedy, 11 September 2001, the Indonesian government should set up a National Measures (National Action Plan), among others formed the National Security Council and NBC Counter Proliferation Unit, or the National Authority for Nuclear Treaty, preparing national legislation, to prevent the abuse nuclear materials for terrorist acts, prevent Illicit Trafficking of Nuclear materials, developed a National Preparedness and Emergency Response Management in the event of a nuclear accident or attack by the use of nuclear terrorism. Importance of a National Action Plan meant the existence of a national commitment in the context of compliance with treaties and conventions which have been ratified relating to safety, security, safeguards towards a general and complete disarmament, to safeguard national security and maintain peace (safeguards) international

  6. Initiatives for proliferation prevention

    International Nuclear Information System (INIS)

    1997-04-01

    Preventing the proliferation of weapons of mass destruction is a central part of US national security policy. A principal instrument of the Department of Energy's (DOE's) program for securing weapons of mass destruction technology and expertise and removing incentives for scientists, engineers and technicians in the newly independent states (NIS) of the former Soviet Union to go to rogue countries or assist terrorist groups is the Initiatives for Proliferation Prevention (IPP). IPP was initiated pursuant to the 1994 Foreign Operations Appropriations Act. IPP is a nonproliferation program with a commercialization strategy. IPP seeks to enhance US national security and to achieve nonproliferation objectives by engaging scientists, engineers and technicians from former NIS weapons institutes; redirecting their activities in cooperatively-developed, commercially viable non-weapons related projects. These projects lead to commercial and economic benefits for both the NIS and the US IPP projects are funded in Russian, Ukraine, Kazakhstan and Belarus. This booklet offers an overview of the IPP program as well as a sampling of some of the projects which are currently underway

  7. One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus

    NARCIS (Netherlands)

    Asseldonk, van E.J.P.; Poppel, van P.C.M.; Ballak, D.B.; Stienstra, Rinke; Netea, M.G.; Tack, C.J.

    2015-01-01

    Inflammation associated with obesity is involved in the development of insulin resistance. We hypothesized that anti-inflammatory treatment with the Interleukin-1 receptor antagonist anakinra would improve insulin sensitivity.In an open label proof-of-concept study, we included overweight

  8. Uncertainties in Nuclear Proliferation Modeling

    International Nuclear Information System (INIS)

    Kim, Chul Min; Yim, Man-Sung; Park, Hyeon Seok

    2015-01-01

    There have been various efforts in the research community to understand the determinants of nuclear proliferation and develop quantitative tools to predict nuclear proliferation events. Such systematic approaches have shown the possibility to provide warning for the international community to prevent nuclear proliferation activities. However, there are still large debates for the robustness of the actual effect of determinants and projection results. Some studies have shown that several factors can cause uncertainties in previous quantitative nuclear proliferation modeling works. This paper analyzes the uncertainties in the past approaches and suggests future works in the view of proliferation history, analysis methods, and variable selection. The research community still lacks the knowledge for the source of uncertainty in current models. Fundamental problems in modeling will remain even other advanced modeling method is developed. Before starting to develop fancy model based on the time dependent proliferation determinants' hypothesis, using graph theory, etc., it is important to analyze the uncertainty of current model to solve the fundamental problems of nuclear proliferation modeling. The uncertainty from different proliferation history coding is small. Serious problems are from limited analysis methods and correlation among the variables. Problems in regression analysis and survival analysis cause huge uncertainties when using the same dataset, which decreases the robustness of the result. Inaccurate variables for nuclear proliferation also increase the uncertainty. To overcome these problems, further quantitative research should focus on analyzing the knowledge suggested on the qualitative nuclear proliferation studies

  9. Proliferation: myth or reality?; La proliferation: mythe ou realite?

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-07-01

    This article analyzes the proliferation approach, its technical condition and political motivation, and the share between the myth (political deception, assumptions and extrapolations) and the reality of proliferation. Its appreciation is complicated by the irrational behaviour of some political actors and by the significant loss of the non-use taboo. The control of technologies is an important element for proliferation slowing down but an efficient and autonomous intelligence system remains indispensable. (J.S.)

  10. The nuclear proliferation

    International Nuclear Information System (INIS)

    Gere, F.

    1995-04-01

    In this book is detailed the beginning of nuclear military power, with the first bomb of Hiroshima, the different ways of getting uranium 235 and plutonium 239, and how the first countries (Usa, Ussr, China, United kingdom, France) got nuclear weapons. Then the most important part is reviewed with the details of non-proliferation treaty and the creation of IAEA to promote civilian nuclear power in the world and to control the use of plutonium and uranium in nuclear power plants. The cases of countries who reached the atom mastery, such Israel, South Africa, Pakistan, Iraq, North Korea, Argentina, Brazil, Iran, Algeria, Taiwan and the reasons which they wanted nuclear weapon for or why they gave up, are exposed

  11. Use of Biomass as a Sustainable and Green Fuel with Alkali-Resistant DeNOx Catalysts based on Sulfated or Tungstated Zirconia

    DEFF Research Database (Denmark)

    Due-Hansen, Johannes; Fehrmann, Rasmus; Christensen, Claus H.

    poisons is the use of supports with highly acidic properties, which would interact stronger with potassium than the vanadium species. Among those, sulfated and tungstated zirconica appears very attractive, since their surface acidity can be tuned in a wide range by varying the preparation procedure, WOX......, sulfated, and tungstated zirconia were prepared and tested. The influence of potassium additives on the acidity and activity was studied and the results were compared with traditional V2O5-WO3/TiO2 catalyst. Resistance of the catalysts towards poisoning with potassium was found to depend dramatically...... on the crystallinity and surface acidity of the support used. Better resistance of the samples based on sulfated and tungstated zirconia seems to be connected with the fact that a significant part of the potassium on the surface of the catalyst preferentially interact with strong acid sites of the support thus...

  12. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Blagden Sarah

    2011-07-01

    Full Text Available Abstract Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.

  13. Sustainable Disruptions

    DEFF Research Database (Denmark)

    Friis, Silje Alberthe Kamille; Kjær, Lykke Bloch

    2016-01-01

    Since 2012 the Sustainable Disruptions (SD) project at the Laboratory for Sustainability at Design School Kolding (DK) has developed and tested a set of design thinking tools, specifically targeting the barriers to economically, socially, and environmentally sustainable business development....... The tools have been applied in practice in collaboration with 11 small and medium sized companies (SMEs). The study investigates these approaches to further understand how design thinking can contribute to sustainable transition in a business context. The study and the findings are relevant to organizations...... invested in the issue of sustainable business development, in particular the leaders and employees of SMEs, but also to design education seeking new ways to consciously handle and teach the complexity inherent in sustainable transformation. Findings indicate that the SD design thinking approach contributes...

  14. Computational sustainability

    CERN Document Server

    Kersting, Kristian; Morik, Katharina

    2016-01-01

    The book at hand gives an overview of the state of the art research in Computational Sustainability as well as case studies of different application scenarios. This covers topics such as renewable energy supply, energy storage and e-mobility, efficiency in data centers and networks, sustainable food and water supply, sustainable health, industrial production and quality, etc. The book describes computational methods and possible application scenarios.

  15. Sustainability of 8% weight loss, reduction of insulin resistance, and amelioration of atherogenic-metabolic risk factors over 4 years by metformin-diet in women with polycystic ovary syndrome.

    Science.gov (United States)

    Glueck, Charles J; Aregawi, Dawit; Agloria, Mahlia; Winiarska, Magdalena; Sieve, Luann; Wang, Ping

    2006-12-01

    In 74 women with polycystic ovary syndrome, treated for 4 years with metformin (MET) and diet, we prospectively assessed whether, and to what degree, weight loss, reduction of insulin resistance, and amelioration of coronary heart disease risk factors could be sustained. We hypothesized that response to MET-diet would not differ by pretreatment body mass index (BMI) classes or =25 to or =30 to or =40 (extremely obese). [table: see text] Metformin-diet was successful in producing stable approximately 8% weight reduction for all 4 years (trend P weight on MET-diet was significant (P or =40, > or =30 to or =25 to weight category (BMI, .1) in the 4 BMI categories. By stepwise regression, weight loss was a significant (P polycystic ovary syndrome effectively and safely reduces weight and LDL-C while raising HDL-C, and maintains these outcomes stable over 4 years.

  16. Sustainable Universities

    DEFF Research Database (Denmark)

    Grindsted, Thomas Skou

    2011-01-01

    Declarations on Sustainability in Higher Education (SHE) can be viewed as a piece of international regulation. Over the past 30 years research at universities has produced convincing data to warn about deterioration of the environment, resource scarcity and the need for sustainability. This in turn....... Declarations tend to have impact on three trends. Firstly, there is emerging international consensus on the university’s role and function in relation to sustainable development; secondly, the emergence of national legislation, and thirdly, an emerging international competition to be leader in sustainable...

  17. Future technology challenges in non-proliferation

    International Nuclear Information System (INIS)

    Richardson, J.H.

    2004-01-01

    Radiation detection technologies are an important tool in the prevention of proliferation. A variety of new developments have enabled enhanced performance in terms of energy resolution, spatial resolution, predictive modeling and simulation, active interrogation, and ease of operation and deployment in the field. For example, various gamma ray imaging approaches are being explored to combine spatial resolution with background suppression in order to enhance sensitivity at reasonable standoff distances and acquisition times. New materials and approaches are being developed in order to provide adequate energy resolution in field use without the necessity for liquid nitrogen. Finally, different detectors combined into distributed networks offer promise for detection and tracking of radioactive materials. As the world moves into the 21st century, the possibility of greater reliance on nuclear energy will impose additional technical requirements to prevent proliferation. In addition to proliferation resistant reactors, a careful examination of the various possible fuel cycles from cradle to grave will provide additional technical and nonproliferation challenges in the areas of conversion, enrichment, transportation, recycling and waste disposal. Radiation detection technology and information management have a prominent role in any future global regime for nonproliferation beyond the current Advanced Protocol. This work was performed under the auspices of the U.S. Department of Energy by University of California, Lawrence Livermore National Laboratory under contract No. W-7405-Eng-48. (author)

  18. Utility of Social Modeling for Proliferation Assessment - Preliminary Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Coles, Garill A.; Gastelum, Zoe N.; Brothers, Alan J.; Thompson, Sandra E.

    2009-06-01

    This Preliminary Assessment draft report will present the results of a literature search and preliminary assessment of the body of research, analysis methods, models and data deemed to be relevant to the Utility of Social Modeling for Proliferation Assessment research. This report will provide: 1) a description of the problem space and the kinds of information pertinent to the problem space, 2) a discussion of key relevant or representative literature, 3) a discussion of models and modeling approaches judged to be potentially useful to the research, and 4) the next steps of this research that will be pursued based on this preliminary assessment. This draft report represents a technical deliverable for the NA-22 Simulations, Algorithms, and Modeling (SAM) program. Specifically this draft report is the Task 1 deliverable for project PL09-UtilSocial-PD06, Utility of Social Modeling for Proliferation Assessment. This project investigates non-traditional use of social and cultural information to improve nuclear proliferation assessment, including nonproliferation assessment, proliferation resistance assessments, safeguards assessments and other related studies. These assessments often use and create technical information about the State’s posture towards proliferation, the vulnerability of a nuclear energy system to an undesired event, and the effectiveness of safeguards. This project will find and fuse social and technical information by explicitly considering the role of cultural, social and behavioral factors relevant to proliferation. The aim of this research is to describe and demonstrate if and how social science modeling has utility in proliferation assessment.

  19. The Fiction of Sustainability

    DEFF Research Database (Denmark)

    Mubanda Rasmussen, Louise

    research with organisations providing help to "Orphans and Vulnerable Children" in Malawi, this paper discusses how donors, international and local NGOs, and CBOs all participate in keeping alive 'the fiction of sustainability', each for their different reasons. Rather than overt resistance to the power...... of international donors, the processes I discuss reflect how actors from their different positions become skilled in using established policy models and available resources for their own ends....

  20. Protected Plutonium Production by Transmutation of Minor Actinides for Peace and Sustainable Prosperity [O1] - Fundamentals of P{sup 3} Mechanism and Methodology Development for Plutonium Categorization

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Masaki [Research Laboratory for Nuclear Reactor, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 1528550 (Japan)

    2009-06-15

    'Protected Plutonium Production (P{sup 3})' has been proposed to enhance the proliferation resistance of plutonium by the transmutation of Minor Actinides (MAs). Doping the small amount of MAs such as {sup 237}Np or {sup 241}Am with large neutron capture cross-section into the uranium fuel to enhance the production of {sup 238}Pu or {sup 242}Pu, which have high spontaneous fission neutron source or also high decay heat to makes the process of the nuclear weapon manufacture and maintenance technologically difficult, can be effective for improving the isotopic barrier of proliferation resistance of the plutonium in thermal reactors. Super weapon grade plutonium could be produced in the blanket of a conventional FBR. However, by increasing the {sup 238}Pu or {sup 242}Pu ratio in the total plutonium by MAs doping into the fresh blanket, the protected plutonium with high proliferation-resistance can be bred. A new evaluation function, 'attractiveness', defined as a ratio of potential of fission yield to the technological difficulties of nuclear explosive device, has been proposed to evaluate the proliferation resistance of Pu based on the nuclear material property for Plutonium Categorization. In the conference, the fundamentals of P{sup 3} mechanism by transmutation of MA, and the comparison of the 'attractiveness' of the Pu produced in advanced reactors based on P{sup 3} mechanism and in the conventional reactors will be presented. Instead of the geological disposal or just their burning of MAs by the fission reaction, they should be treated as valuable fertile materials to enhance the proliferation resistance of plutonium produced in the thermal and fast breeder reactors for peace and sustainable prosperity in future. Acknowledgement: Some parts of this work have been supported by the Ministry of Education, Culture, Sports, Science and Technology in Japan. (authors)

  1. Sustainable Transition

    DEFF Research Database (Denmark)

    Hansen, Ole Erik; Søndergård, Bent

    2014-01-01

    of agendas/vision, technologies, actors and institutions in the emergent design of an urban mobility system based on an electric car sharing system. Why. Designing for sustainability is a fundamental challenge for future design practices; designers have to obtain an ability to contribute to sustainable...

  2. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuil...

  3. Sustainability Labeling

    NARCIS (Netherlands)

    Dam, van Y.K.

    2017-01-01

    Sustainability labeling originated from a need to protect the identity of alternative systems of food production and to increase market transparency. From the 1980s onwards sustainability labeling has changed into a policy instrument replacing direct government regulation of the food market, and a

  4. A Conceptual Study on the Sustainability of Nuclear Power

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Won Il; Kwon, Eun Ha; Choi, Hang Bok; Lim, Chae Young; Yoon, Ji Sup; Park, Seong Won

    2007-06-15

    Due to the current population growth and industrialization, energy consumption is increasing continuously. The world population and energy consumption were 2.5 billion and 1.5 billion tons of equivalent oil in 1950, but they are expected to be 9.2 billion and 60 tons, respectively, in 2100. This amount of energy consumption will result in an exhaustion of fossil resources and cause a serious environmental problem such as global warming. Therefore it is necessary to develop sustainable energy resources that maintain current economic growth and social welfare level without burdening a next generation's life style. Nuclear energy has an excellent competitiveness from the viewpoint of a sustainability. Especially nuclear power can effectively reduce greenhouse gas emissions and can be developed in a complementary way with a new and renewable energy, such as solar and wind power, and hydrogen energy. It is expected that nuclear power will maintain its sustainability in the following directions: Implementation of a fast reactor fuel cycle with a high uranium utilization efficiency, Implementation of a pyro-process with an excellent proliferation-resistance, Activity on the enhancement of a domestic social acceptance for nuclear power, International cooperation and joint research for the enhancement of an international nuclear transparency, Optimization of a nuclear grid structure through an accommodation of new and renewable energy resources, Application to a mass production of hydrogen energy.

  5. Afterschool Sustainability

    Directory of Open Access Journals (Sweden)

    Hilary D. Joyce

    2014-12-01

    Full Text Available Youth participation in quality extended learning opportunities (ELOs results in positive academic, physical, mental health, and social/emotional outcomes. Funding is essential to implementing and sustaining quality ELOs; however multiple funding barriers and challenges exist. Understanding the types of funds available for ELOs and the factors that influence sustainability is critical. Through surveys and telephone interviews of ELO providers, this descriptive study identified and examined ELO funding streams, the ways ELO providers use these funding streams, and the barriers and challenges to sustainability. ELO programs often relied on one major funding stream coupled with nutrition supports as well as in-kind resources. Barriers to sustainability included year-to-year funding, transportation costs, reducing community partnerships, and difficulty in diversifying funds. Recommendations to enhance ELO sustainability are offered, particularly in relation to overcoming the challenges to diversification of funding resources and establishing mutually supportive partnerships and collaboration.

  6. Nuclear proliferation: linkages and solutions

    International Nuclear Information System (INIS)

    Quester, G.H.

    1979-01-01

    Nuclear proliferation must be periodically re-examined as a moral as well as a practical foreign policy dilemma. The question is asked whether proliferation precludes a safe and peaceful world, or if a halt to proliferation is adequate without other arms control. The moral dilemma in foreign policy arises over the need to make practical choices which often serve one goal while sacrificing another. The ramifications of nuclear proliferation are examined and the conclusions reached that it is not an acceptable option. It is also decided that, because general disarmament steps will be more difficult to achieve, the world may have to accept a small number of nuclear arsenals as the price of state sovereignties. A high priority for making the effort to prevent proliferation is advised. 8 references

  7. Plutonium Proliferation: The Achilles Heel of Disarmament

    International Nuclear Information System (INIS)

    Leventhal, Paul

    2001-01-01

    Plutonium is a byproduct of nuclear fission, and it is produced at the rate of about 70 metric tons a year in the world's nuclear power reactors. Concerns about civilian plutonium ran high in the 1970s and prompted enactment of the Nuclear Non-Proliferation Act of 1978 to give the United States a veto over separating plutonium from U.S.-supplied uranium fuel. Over the years, however, so-called reactor-grade plutonium has become the orphan issue of nuclear non-proliferation, largely as a consequence of pressures from plutonium-separating countries. The demise of the fast breeder reactor and the reluctance of utilities to introduce plutonium fuel in light-water reactors have resulted in large surpluses of civilian, weapons-usable plutonium, which now approach in size the 250 tons of military plutonium in the world. Yet reprocessing of spent fuel for recovery and use of plutonium proceeds apace outside the United States and threatens to overwhelm safeguards and security measures for keeping this material out of the hands of nations and terrorists for weapons. A number of historical and current developments are reviewed to demonstrate that plutonium commerce is undercutting efforts both to stop the spread of nuclear weapons and to work toward eliminating existing nuclear arsenals. These developments include the breakdown of U.S. anti-plutonium policy, the production of nuclear weapons by India with Atoms-for-Peace plutonium, the U.S.-Russian plan to introduce excess military plutonium as fuel in civilian power reactors, the failure to include civilian plutonium and bomb-grade uranium in the proposed Fissile Material Cutoff Treaty, and the perception of emerging proliferation threats as the rationale for development of a ballistic missile defense system. Finally, immobilization of separated plutonium in high-level waste is explored as a proliferation-resistant and disarmament-friendly solution for eliminating excess stocks of civilian and military plutonium.

  8. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Science.gov (United States)

    Zielińska, Karolina A.; de Cauwer, Lode; Knoops, Sofie; Van der Molen, Kristof; Sneyers, Alexander; Thommis, Jonathan; De Souza, J. Brian; Opdenakker, Ghislain; De Bosscher, Karolien; Van den Steen, Philippe E.

    2017-01-01

    Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs) have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ) and Plasmodium berghei NK65 (PbNK65). Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES) by 90% and both CCL2 (MCP-1) and CXCL10 (IP-10) by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1) unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK), JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs. PMID:29033931

  9. Plasmodium berghei NK65 in Combination with IFN-γ Induces Endothelial Glucocorticoid Resistance via Sustained Activation of p38 and JNK

    Directory of Open Access Journals (Sweden)

    Karolina A. Zielińska

    2017-09-01

    Full Text Available Malaria-associated acute respiratory distress syndrome (MA-ARDS is an often lethal complication of malaria. Currently, no adequate therapy for this syndrome exists. Although glucocorticoids (GCs have been used to improve clinical outcome of ARDS, their therapeutic benefits remain unclear. We previously developed a mouse model of MA-ARDS, in which dexamethasone treatment revealed GC resistance. In the present study, we investigated GC sensitivity of mouse microvascular lung endothelial cells stimulated with interferon-γ (IFN-γ and Plasmodium berghei NK65 (PbNK65. Upon challenge with IFN-γ alone, dexamethasone inhibited the expression of CCL5 (RANTES by 90% and both CCL2 (MCP-1 and CXCL10 (IP-10 by 50%. Accordingly, whole transcriptome analysis revealed that dexamethasone differentially affected several gene clusters and in particular inhibited a large cluster of IFN-γ-induced genes, including chemokines. In contrast, combined stimulation with IFN-γ and PbNK65 extract impaired inhibitory actions of GCs on chemokine release, without affecting the capacity of the GC receptor to accumulate in the nucleus. Subsequently, we investigated the effects of GCs on two signaling pathways activated by IFN-γ. Dexamethasone left phosphorylation and protein levels of signal transducer and activator of transcription 1 (STAT1 unhampered. In contrast, dexamethasone inhibited the IFN-γ-induced activation of two mitogen-activated protein kinases (MAPK, JNK, and p38. However, PbNK65 extract abolished the inhibitory effects of GCs on MAPK signaling, inducing GC resistance. These data provide novel insights into the mechanisms of GC actions in endothelial cells and show how malaria may impair the beneficial effects of GCs.

  10. Thorium cycles and proliferation

    International Nuclear Information System (INIS)

    Lovins, A.B.

    1979-01-01

    This paper analyzes several prevalent misconceptions about nuclear fuel cycles that breed fissile uranium-233 from thorium. Its main conclusions are: U-233, despite the gamma radioactivity of associated isotopes, is a rather attractive material for making fission bombs, and is a credible material for subnational as well as national groups to use for this purpose; (2) pure thorium cycles, which in effect merely substitute U-233 for Pu, would take many decades and much U to establish, and offer no significant safeguards advantage over Pu, cycles; (3) denatured Th-U cycles, which dilute the U-233 with inert U-238 to a level not directly usable in bombs, are not an effective safeguard even against subnational bomb-making; (4) several other features of mixed Th-U cycles are rather unattractive from a safeguards point of view; (5) thus, Th cycles of any kind are not a technical fix for proliferation (national or subnational) and, though probably more safeguardable than Pu cycles, are less so than once-through U cycles that entail no reprocessing; (6) while thorium cycles have some potential technical advantages, including flexibility, they cannot provide major savings in nuclear fuel resources compared to simpler ways of saving neutrons and U; and (7) while advocates of nuclear power may find Th cycles worth exploring, such cycles do not differ fundamentally from U cycles in any of the respects--including safeguards and fuel resources--that are relevant to the broader nuclear debate, and should not be euphorically embraced as if they did

  11. Sustainable Cities

    DEFF Research Database (Denmark)

    Georg, Susse; Garza de Linde, Gabriela Lucía

    Judging from the number of communities and cities striving or claiming to be sustainable and how often eco-development is invoked as the means for urban regeneration, it appears that sustainable and eco-development have become “the leading paradigm within urban development” (Whitehead 2003....../assessment tool. The context for our study is urban regeneration in one Danish city, which had been suffering from industrial decline and which is currently investing in establishing a “sustainable city”. Based on this case study we explore how the insights and inspiration evoked in working with the tool...

  12. Theoretical Approaches to Nuclear Proliferation

    Directory of Open Access Journals (Sweden)

    Konstantin S. Tarasov

    2015-01-01

    Full Text Available This article analyses discussions between representatives of three schools in the theory of international relations - realism, liberalism and constructivism - on the driving factors of nuclear proliferation. The paper examines major theoretical approaches, outlined in the studies of Russian and foreign scientists, to the causes of nuclear weapons development, while unveiling their advantages and limitations. Much of the article has been devoted to alternative approaches, particularly, the role of mathematical modeling in assessing proliferation risks. The analysis also reveals a variety of different approaches to nuclear weapons acquisition, as well as the absence of a comprehensive proliferation theory. Based on the research results the study uncovers major factors both favoring and impeding nuclear proliferation. The author shows that the lack of consensus between realists, liberals and constructivists on the nature of proliferation led a number of scientists to an attempt to explain nuclear rationale by drawing from the insights of more than one school in the theory of IR. Detailed study of the proliferation puzzle contributes to a greater understating of contemporary international realities, helps to identify mechanisms that are most likely to deter states from obtaining nuclear weapons and is of the outmost importance in predicting short- and long-term security environment. Furthermore, analysis of the existing scientific literature on nuclear proliferation helps to determine future research agenda of the subject at hand.

  13. Animation of Antimicrobial Resistance

    Medline Plus

    Full Text Available ... Pin it Email Print The Food and Drug Administration's (FDA's) Center for Veterinary Medicine (CVM) produced a nine-minute animation explaining how antimicrobial resistance both emerges and proliferates among bacteria. Over time, the use of antimicrobial drugs will result in ...

  14. Nuclear non proliferation and disarmament

    International Nuclear Information System (INIS)

    2000-01-01

    In the framework of the publication of a document on the ''weapons mastership, disarmament and non proliferation: the french action'', by the ministry of Foreign Affairs and the ministry of Defense, the French Documentation organization presents a whole document. This document describes and details the following topics: the conference on the treaty of non proliferation of nuclear weapons, the France, Usa and Non Governmental Organizations position, the threats of the proliferation, the french actions towards the disarmament, the disarmament in the world, a chronology and some bibliographic resources. (A.L.B.)

  15. International proliferation on nuclear weapons

    International Nuclear Information System (INIS)

    Hill, J.

    1977-01-01

    The subject is dealt with under the following headings: introduction; routes to proliferation (preparation of U 235 , Pu 239 , U 233 ); nuclear power fuel cycles and proliferation; the fast reactor fuel cycle; security aspects of the existing fuel cycle; the IAEA and the nuclear non-proliferation treaty. It is concluded that 'the basis for sound international control exists, and taken together with the further technical steps which will be taken to make the existing fuel cycles more robust against the diversion of materials by terrorists and the abuse of civil nuclear power programmes by governments, we have good reason to proceed now with the orderly exploitation of ...nuclear energy...'. (U.K.)

  16. Sustainable Transportation

    DEFF Research Database (Denmark)

    Hall, Ralph P.; Gudmundsson, Henrik; Marsden, Greg

    2014-01-01

    The transportation system is the backbone of economic and social progress and the means by which humans access goods and services and connect with one another. Yet, as the scale of transportation activities has grown worldwide, so too have the negative environmental, social, and economic impacts...... that relate to the construction and maintenance of transportation infrastructure and the operation or use of the different transportation modes. The concept of sustainable transportation emerged in response to these concerns as part of the broader notion of sustainable development. Given the transportation...... sector’s significant contribution to global challenges such as climate change, it is often said that sustainable development cannot be achieved without sustainable transportation....

  17. Agriculture: Sustainability

    Science.gov (United States)

    Sustainability creates and maintains the conditions under which humans and nature can exist in productive harmony, that permit fulfilling the food, feed, and fiber needs of our country and the social, economic and other requirements.

  18. Sustainable consumption

    DEFF Research Database (Denmark)

    Prothero, Andrea; Dobscha, Susan; Freund, Jim

    2011-01-01

    This essay explores sustainable consumption and considers possible roles for marketing and consumer researchers and public policy makers in addressing the many sustainability challenges that pervade our planet. Future research approaches to this interdisciplinary topic need to be comprehensive...... and systematic and will benefit from a variety of different perspectives. There are a number of opportunities for future research, and three areas are explored in detail. First, the essay considers the inconsistency between the attitudes and behaviors of consumers with respect to sustainability; next, the agenda...... is broadened to explore the role of individual citizens in society; and finally, a macro institutional approach to fostering sustainability is explored. Each of these areas is examined in detail and possible research avenues and public policy initiatives are considered within each of these separate...

  19. Sustainable Futures

    Science.gov (United States)

    Sustainable Futures is a voluntary program that encourages industry to use predictive models to screen new chemicals early in the development process and offers incentives to companies subject to TSCA section 5.

  20. Sustainability reporting

    NARCIS (Netherlands)

    Kolk, A.

    2005-01-01

    This article gives an overview of developments in sustainability (also sometimes labelled corporate social responsibility) reporting. The article will first briefly indicate how accountability on social and environmental issues started, already in the 1970s when social reports were published.

  1. Sustainable transformation

    DEFF Research Database (Denmark)

    Andersen, Nicolai Bo

    This paper is about sustainable transformation with a particular focus on listed buildings. It is based on the notion that sustainability is not just a question of energy conditions, but also about the building being robust. Robust architecture means that the building can be maintained and rebuilt......, that it can be adapted to changing functional needs, and that it has an architectural and cultural value. A specific proposal for a transformation that enhances the architectural qualities and building heritage values of an existing building forms the empirical material, which is discussed using different...... theoretical lenses. It is proposed that three parameters concerning the ꞌtransformabilityꞌ of the building can contribute to a more nuanced understanding of sustainable transformation: technical aspects, programmatic requirements and narrative value. It is proposed that the concept of ꞌsustainable...

  2. Sustainable Consumption

    DEFF Research Database (Denmark)

    Røpke, Inge

    2015-01-01

    The intention of this chapter is to explore the role of consumption and consumers in relation to sustainability transition processes and wider systemic transformations. In contrast to the individualistic focus in much research on sustainable consumption, the embeddedness of consumption activities...... in wider social, economic and technological frameworks is emphasised. In particular, the chapter is inspired by practice theory and transition theory. First, various trends in consumption are outlined to highlight some of the challenges for sustainability transitions. Then, it is discussed how consumption...... patterns are shaped over time and what should be considered in sustainability strategies. While discussions on consumption often take their point of departure in the perspective of the individual and then zoom to the wider context, the present approach is the opposite. The outline starts with the basic...

  3. Stabilizing Sustainability

    DEFF Research Database (Denmark)

    Reitan Andersen, Kirsti

    The publication of the Brundtland Report in 1987 put the topic of sustainable development on the political and corporate agenda. Defining sustainable development as “a development that meets the needs of the future without compromising the ability of future generations to meet their own needs......” (WCED, 1987, p. 43), the Report also put a positive spin on the issue of sustainability by upholding capitalist beliefs in the possibility of infinite growth in a world of finite resources. While growth has delivered benefits, however, it has done so unequally and unsustainably. This thesis focuses...... on the textile and fashion industry, one of the world’s most polluting industries and an industry to some degree notorious for leading the ‘race to the bottom’ in global labour standards. Despite being faced with increasing demands to practise sustainability, most textile and fashion companies continue to fail...

  4. Nuclear proliferation: past, present, and future

    International Nuclear Information System (INIS)

    Bundy, M.

    1983-01-01

    Three things can be learned from the past and present that might tell us how to get a larger share of attention for nuclear nonproliferation. First, a decision to develop nuclear weapons has always been a conscious, serious, deliberate choice by the head of the government concerned. The complicated historical record of our and other country's efforts in this field suggests that no country can have a coherent policy on proliferation unless the subject enjoys the sustained attention of a leader, nearly always a head of government, who is able to make his purposes clearly understood and to ensure that they are persistently carried through. The most important contribution any one country can make is to exhibit understanding and restraint in its own appetite for nuclear solution, economic as well as military. The US is in a favorable position to take a lead, even a unilateral lead, in reducing the number of nuclear weapons. 1 reference

  5. Seeking Sustainability

    OpenAIRE

    Clive L. Spash

    2014-01-01

    What does sustainability research do to help the environment? One might well wonder when observing the annual conference season with various academics and professors in sustainability science, ecological economics or environmental ethics driving to the airport to fly off to international meetings to discuss how bad things are getting, what should been done about it, and how time is running out for action. In fact, singling out a few academic groups is highly unfair because the link between pr...

  6. Local Sustainability

    International Nuclear Information System (INIS)

    Carrizosa Umana, Julio

    1998-01-01

    The current polemic about the possibilities of sustainable development has led to a renovated interest for the topic of the sustainability of the communities and the local sustainability. In front of the global sustainability whose conditions have been exposed by systemic ecologists and for macro economists, the sustainability of specific places arises in the planet whose conditions are object of study of the ecology of landscapes, of the ecological economy, of the cultural anthropology, of the environmental sociology and naturally, of the integral environmentalism. In this discussion the Colombian case charges unusual interest to be one of the few countries of Latin America, where a very dense net of municipalities exists, each one with its urban helmet and with a position and some functions defined by the political constitution of the nation. This net of municipalities and of urban helmets it also constitutes net of alternative to the current macro-cephalic situation. As well as Bogota grew, in a hundred years, of less than a hundred thousand inhabitants to six million inhabitants, each one of these municipalities contains a potential of growth that depends on the characteristics of its ecological, social, economic and politic sustainability

  7. From nuclear non-proliferation to nuclear disarmament: a need to refocus NPT priorities

    International Nuclear Information System (INIS)

    Sethi, Manpreet

    1998-01-01

    This paper seeks to suggest that attempts at general and complete nuclear disarmament have largely failed because of an over emphasis on nuclear non-proliferation, particularly horizontal, while disarmament has attracted only lip service from the perpetrators of nuclear weapons. In this regard, the treaty of the Non-Proliferation of Nuclear Weapons (NPT) that is deemed to be the core of the global non-proliferation regime is no less to blame for having indulged in a skewed pursuit of its twin objectives - nuclear non-proliferation and nuclear disarmament. The paper argues that nuclear non-proliferation can be sustainable only if complemented by nuclear disarmament. In the absence of the latter, proliferation of nuclear weapons, irrespective of the NPT and its safeguards regime, would always pose a potential risk

  8. Sustainable markets for sustainable energy

    Energy Technology Data Exchange (ETDEWEB)

    Millan, J.; Smyser, C.

    1997-12-01

    The author discusses how the Inter-American Development Bank (IDB) is involved in sustainable energy development. It presently has 50 loans and grants for non conventional renewable energy projects and ten grants for efficiency programs for $600 and $17 million respectively, representing 100 MW of power. The IDB is concerned with how to create a sustainable market for sustainable energy projects. The IDB is trying to work with government, private sector, NGOs, trading allies, credit sources, and regulators to find proper roles for such projects. He discusses how the IDB is working to expand its vision and objectives in renewable energy projects in Central and South America.

  9. Non-proliferation and nuclear data

    International Nuclear Information System (INIS)

    Sowerby, M.G.

    1978-01-01

    A review is made of the problem of the proliferation of nuclear weapons with particular emphasis on proliferation and nuclear power. Some indications of the nuclear data requirements associated with methods of reducing proliferation risks are presented

  10. The US proliferation security initiative (PSI); L'initiative americaine de securite contre la proliferation (PSI)

    Energy Technology Data Exchange (ETDEWEB)

    Gregoire, B

    2004-10-01

    The proliferation security initiative (PSI), launched by President Bush on May 31, 2003, aims at intercepting any transfer of mass destruction weapons, of their vectors and related equipments, towards or coming from countries or organizations suspected to have a proliferation activity. This initiative, which involves coercive means to fight against proliferation, raises international lawfulness and legal questions, the answers of which are today under construction. This article analyzes the place of the European Union in the PSI, the action means (optimization of existing means, cooperation between intelligence and interception services), and the PSI stakes (lawfulness with respect to the international law, bilateral agreements, draft boarding agreement, sustain of the United Nations, widening of the partnership and of the field of action). (J.S.)

  11. Nuclear energy and proliferation: A longer perspective

    International Nuclear Information System (INIS)

    Weinberg, A.M.

    1985-01-01

    Nuclear power has expanded slowly; and it is largely based on reactors that require no recycle. The original basis for concern about proliferation - that nuclear power would be used very widely and that it would be based on systems that required reprocessing - has been shaken. The present world nuclear energy system, which is small and based on no-recycle reactors, is relatively resistant to proliferation via diversion from power reactors. Though worry about proliferation can never be eliminated, the perceived connection between power and bombs can be slowly reduced. The proposal to link fuel take-back with waste disposal poses a dilemma for the ''nuclear environmental'' activists. This group objects to nuclear power because, in their view, reactor wastes threaten the environment, and because bombs and reactors are connected. Both objections are held, often passionately; it would be difficult to assess which takes primacy. This proposal further breaks the ''Nuclear Connection,'' but at the expense of adding a little to the volume of wastes the United States would have to dispose of. We are in effect saying that the loosening of the nuclear connection through the take-back scheme should take precedence over the tiny environmental burden incurred by the addition of a few percent to the total wastes the U.S. already must dispose of. It is hoped that the nuclear environmental community will recognize this trade-off, and will help create the atmosphere of public understanding necessary if fuel take-back is to be accepted in the United States

  12. Proliferation prevention in the commercial fuel cycle

    International Nuclear Information System (INIS)

    Sutcliffe, W.G.

    1999-01-01

    This website contains the papers presented on November 17, 1998 during the session, ''Proliferation Prevention in the Commercial Fuel Cycle,'' at the American Nuclear Society meeting in Washington, DC. The abstracts are in a separate section; individual papers also contain the author's bio and e-mail address. In the session planning phase, it was suggested that the following questions and other relevant issues be addressed: * What are the difficulties and issues with defining and enforcing international standards for the physical protection of Pu and HEU (beyond the Convention on the Physical protection of Nuclear Material, which primarily addresses transportation)? * How do we (or can we) keep nuclear technology in general, and reprocessing and enrichment technologies in particular, from spreading to undesirable organizations (including governments), in light of Article IV of the NPT? Specifically, can we (should we) prevent the construction of light-water reactors in Iran; and should we support the construction of light-water reactors in North Korea? * Are there more proliferation-resistant fuel cycles that would be appropriate in developing countries? * Can the concept of ''nonproliferation credentials'' be defined in a useful way? * Is there historical evidence to indicate that reprocessing (or enrichment of HEU) in the US, Japan, or the EURATOM countries has impacted the acquisition (or attempted acquisition) of nuclear weapons by other nations or groups? * What is the impact of a fissile material cutoff treaty (FMCT) be on commercial nuclear fuel cycles? * Does MOX spent fuel present a greater proliferation risk than LEU spent fuel? Although the authors did not explicitly attempt to answer all these questions, they did enlighten us about a number of these and related issues

  13. United Nations study on disarmament and non-proliferation education

    International Nuclear Information System (INIS)

    2003-01-01

    Science and technology transformed the world in the twentieth century. Living standards improved but warfare was rendered more deadly. Weapons of mass destruction - biological, chemical and nuclear - and their means of delivery were developed, as ever more sophisticated conventional armaments were produced and disseminated. The horrors and destruction of armed conflict persist. The need for disarmament and non-proliferation education and training has never been greater. Indeed, changing concepts and perceptions of security and threat magnify the urgency for new thinking to pursue disarmament and non-proliferation goals. More than a decade after the end of the cold war and at the start of the twenty- first century, there is a pressing need to combat ignorance, complacency and a culture of violence. These can be countered through long-term programmes of education and training, especially those related to disarmament and non- proliferation of weapons of mass destruction and their means of delivery, with a view to their reduction and complete elimination. At the same time, concern has heightened over the global threat of the excessive and destabilizing proliferation of conventional weapons, especially small arms and light weapons, rendering more acute the need to combat such proliferation in a sustained way through disarmament and non-proliferation education and training. Additionally there is a need to raise awareness of new challenges to international security and the process of disarmament. Among them, terrorism, with the possibility of the use of weapons of mass destruction, is a source of particular concern. Other challenges, such as organized crime, poverty, human rights abuses and environmental concerns must also be taken into account. Education and training remain important but under utilized tools for promoting peace, disarmament and non-proliferation. The present report addresses that issue and proposes ideas for action

  14. Roundtabling Sustainability

    DEFF Research Database (Denmark)

    Ponte, Stefano

    2014-01-01

    councils’ and ‘sustainability roundtables’ and have been designed around a set of institutional features seeking to establish legitimacy, fend off possible criticism, and ‘sell’ certifications to potential users. The concept of ‘roundtabling’ emphasizes the fitting a variety of commodity...... and procedures to meet ‘good practice’ in standard setting and management. This is opening space for competing initiatives that are less democratic, quicker, and more aligned with industry interests to establish substantial presence in the market for sustainability certifications. These tend to more easily...

  15. Where Is "Community"?: Engineering Education and Sustainable Community Development

    Science.gov (United States)

    Schneider, J.; Leydens, J. A.; Lucena, J.

    2008-01-01

    Sustainable development initiatives are proliferating in the US and Europe as engineering educators seek to provide students with knowledge and skills to design technologies that are environmentally sustainable. Many such initiatives involve students from the "North," or "developed" world building projects for villages or…

  16. Is light water reactor technology sustainable?

    International Nuclear Information System (INIS)

    Rothwell, G.; Van der Zwaan, B.

    2001-01-01

    This paper proposes criteria for determining ''intermediate sustainability'' over a 500-year horizon. We apply these criteria to Light Water Reactor (LWR) technology and the LWR industry. We conclude that LWR technology does not violate intermediate sustainability criteria for (1) environmental externalities, (2) worker and public health and safety, or (3) accidental radioactive release. However, it does not meet criteria to (1) efficiently use depleted uranium and (2) avoid uranium enrichment technologies that can lead to nuclear weapons proliferation. Finally, current and future global demand for LWR technology might be below the minimum needed to sustain the current global LWR industry. (author)

  17. Is light water reactor technology sustainable?

    Energy Technology Data Exchange (ETDEWEB)

    Rothwell, G. [Stanford Univ., Dept. of Economics, CA (United States); Van der Zwaan, B. [Vrije Univ., Amsterdam, Inst. for Environmental Studies (Netherlands)

    2001-07-01

    This paper proposes criteria for determining ''intermediate sustainability'' over a 500-year horizon. We apply these criteria to Light Water Reactor (LWR) technology and the LWR industry. We conclude that LWR technology does not violate intermediate sustainability criteria for (1) environmental externalities, (2) worker and public health and safety, or (3) accidental radioactive release. However, it does not meet criteria to (1) efficiently use depleted uranium and (2) avoid uranium enrichment technologies that can lead to nuclear weapons proliferation. Finally, current and future global demand for LWR technology might be below the minimum needed to sustain the current global LWR industry. (author)

  18. Soil biodiversity for agricultural sustainability

    NARCIS (Netherlands)

    Brussaard, L.; Ruiter, de P.C.; Brown, G.G.

    2007-01-01

    We critically highlight some evidence for the importance of soil biodiversity to sustaining (agro-)ecosystem functioning and explore directions for future research. We first deal with resistance and resilience against abiotic disturbance and stress. There is evidence that soil biodiversity does

  19. Sustainable finance

    NARCIS (Netherlands)

    Boersma-de Jong, Margreet F.

    2012-01-01

    Presentation for Springschool of Strategy, University of Groningen, 10 October 2012. The role of CSR is to stimulate ethical behaviour, and as a result, mutual trust in society. Advantage of CSR for the company and the evolution of CSR. From CSR to Sustainable Finance: how does CSR influence

  20. Sustainable Procurement

    DEFF Research Database (Denmark)

    Telles, Pedro; Ølykke, Grith Skovgaard

    2017-01-01

    and within it how sustainable requirements have increased the level of compliance required, particularly regulatory compliance. Compliance was already present in previous EU public procurement frameworks, but its extent on Directive 2014/24/EU leads the authors to consider the current legal framework...

  1. Exergy sustainability.

    Energy Technology Data Exchange (ETDEWEB)

    Robinett, Rush D. III (.; ); Wilson, David Gerald; Reed, Alfred W.

    2006-05-01

    Exergy is the elixir of life. Exergy is that portion of energy available to do work. Elixir is defined as a substance held capable of prolonging life indefinitely, which implies sustainability of life. In terms of mathematics and engineering, exergy sustainability is defined as the continuous compensation of irreversible entropy production in an open system with an impedance and capacity-matched persistent exergy source. Irreversible and nonequilibrium thermodynamic concepts are combined with self-organizing systems theories as well as nonlinear control and stability analyses to explain this definition. In particular, this paper provides a missing link in the analysis of self-organizing systems: a tie between irreversible thermodynamics and Hamiltonian systems. As a result of this work, the concept of ''on the edge of chaos'' is formulated as a set of necessary and sufficient conditions for stability and performance of sustainable systems. This interplay between exergy rate and irreversible entropy production rate can be described as Yin and Yang control: the dialectic synthesis of opposing power flows. In addition, exergy is shown to be a fundamental driver and necessary input for sustainable systems, since exergy input in the form of power is a single point of failure for self-organizing, adaptable systems.

  2. Sustainable Buildings

    DEFF Research Database (Denmark)

    Tommerup, Henrik M.; Elle, Morten

    The scientific community agrees that: all countries must drastically and rapidly reduce their CO2 emissions and that energy efficient houses play a decisive role in this. The general attitude at the workshop on Sustainable Buildings was that we face large and serious climate change problems...

  3. Sustainable Entrepreneurship

    DEFF Research Database (Denmark)

    Schaltegger, Stefan; Beckmann, Markus; Hockerts, Kai

    2018-01-01

    . We also explore the transformation path of the case company, which starts with simple use and then moves to the feedback to core business pattern. By drawing on insights from lead user theory in innovation management and sustainable entrepreneurship, we ground the new concept in extant literature...

  4. Sustainable machining

    CERN Document Server

    2017-01-01

    This book provides an overview on current sustainable machining. Its chapters cover the concept in economic, social and environmental dimensions. It provides the reader with proper ways to handle several pollutants produced during the machining process. The book is useful on both undergraduate and postgraduate levels and it is of interest to all those working with manufacturing and machining technology.

  5. Sustainable processing

    DEFF Research Database (Denmark)

    Kristensen, Niels Heine

    2004-01-01

    Kristensen_NH and_Beck A: Sustainable processing. In Otto Schmid, Alexander Beck and Ursula Kretzschmar (Editors) (2004): Underlying Principles in Organic and "Low-Input Food" Processing - Literature Survey. Research Institute of Organic Agriculture FiBL, CH-5070 Frick, Switzerland. ISBN 3-906081-58-3...

  6. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  7. Sustainable development

    International Nuclear Information System (INIS)

    Boiteux, M.

    2004-01-01

    Marcel Boiteux evokes the results of the work on the sustainable development by the Academie des Sciences Morales et Politiques. This is a vast political programme with the goal of allowing all humanity to live well in growing unity while protecting the environment and favouring economic growth. (author)

  8. Sustainable Development

    African Journals Online (AJOL)

    Tsegai Berhane Ghebretekle

    Ethiopia is selected as a case study in light of its pace in economic growth ... Interrogating the Economy-First Paradigm in 'Sustainable Development' … 65 .... agreement, since such effective global cooperation on climate change ultimately ..... and foster innovation; reduce inequality within and among countries; make cities.

  9. Sustainable Soesterkwartier

    NARCIS (Netherlands)

    Abrahams, H.; Goosen, H.; Jong, de F.; Sickmann, J.; Prins, D.

    2010-01-01

    The municipality of Amersfoort wants to construct an endurable and sustainable eco-town in the Soesterkwartier neighbourhood, by taking future climate change into account. The impact of climate change at the location of the proposed eco-town was studied by a literature review.

  10. Sustainable Sizing.

    Science.gov (United States)

    Robinette, Kathleen M; Veitch, Daisy

    2016-08-01

    To provide a review of sustainable sizing practices that reduce waste, increase sales, and simultaneously produce safer, better fitting, accommodating products. Sustainable sizing involves a set of methods good for both the environment (sustainable environment) and business (sustainable business). Sustainable sizing methods reduce (1) materials used, (2) the number of sizes or adjustments, and (3) the amount of product unsold or marked down for sale. This reduces waste and cost. The methods can also increase sales by fitting more people in the target market and produce happier, loyal customers with better fitting products. This is a mini-review of methods that result in more sustainable sizing practices. It also reviews and contrasts current statistical and modeling practices that lead to poor fit and sizing. Fit-mapping and the use of cases are two excellent methods suited for creating sustainable sizing, when real people (vs. virtual people) are used. These methods are described and reviewed. Evidence presented supports the view that virtual fitting with simulated people and products is not yet effective. Fit-mapping and cases with real people and actual products result in good design and products that are fit for person, fit for purpose, with good accommodation and comfortable, optimized sizing. While virtual models have been shown to be ineffective for predicting or representing fit, there is an opportunity to improve them by adding fit-mapping data to the models. This will require saving fit data, product data, anthropometry, and demographics in a standardized manner. For this success to extend to the wider design community, the development of a standardized method of data collection for fit-mapping with a globally shared fit-map database is needed. It will enable the world community to build knowledge of fit and accommodation and generate effective virtual fitting for the future. A standardized method of data collection that tests products' fit methodically

  11. The sustainable nuclear energy technology platform. A vision report

    International Nuclear Information System (INIS)

    2007-01-01

    Nuclear fission energy can deliver safe, sustainable, competitive and practically carbon-free energy to Europe's citizens and industries. Within the framework of the Strategic Energy Technology Plan (SET Plan), the European Commission's stakeholders in this field have formulated a collective vision of the contributions this energy could make towards Europe's transition to a low-carbon energy mix by 2050, with the aim of integrating and expanding R and D capabilities in order to further this objective. The groundwork has been prepared by the stakeholders listed in Annex II, within the framework of two EURATOM FP6 (Sixth Framework Programme) Coordination Actions, namely SNF-TP (Sustainable Nuclear Fission Technology Platform) and PATEROS (Partitioning and Transmutation European Road-map for Sustainable Nuclear Energy), with contributions from Europe's technical safety organisations. This vision report prepares the launch of the European Technology Platform on Sustainable Nuclear Energy (SNE-TP). It proposes a vision for the short-, medium- and long-term development of nuclear fission energy technologies, with the aim of achieving a sustainable production of nuclear energy, a significant progress in economic performance, and a continuous improvement of safety levels as well as resistance to proliferation. In particular, this document proposes road-maps for the development and deployment of potentially sustainable nuclear technologies, as well as actions to harmonize Europe's training and education, whilst renewing its research infrastructures. Public acceptance is also an important issue for the development of nuclear energy. Therefore, research in the fields of nuclear installation safety, protection of workers and populations against radiation, management of all types of waste, and governance methodologies with public participation will be promoted. The proposed road-maps provide the backbone for a strategic research agenda (SRA) to maintain Europe's leadership in

  12. The sustainable nuclear energy technology platform. A vision report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    Nuclear fission energy can deliver safe, sustainable, competitive and practically carbon-free energy to Europe's citizens and industries. Within the framework of the Strategic Energy Technology Plan (SET Plan), the European Commission's stakeholders in this field have formulated a collective vision of the contributions this energy could make towards Europe's transition to a low-carbon energy mix by 2050, with the aim of integrating and expanding R and D capabilities in order to further this objective. The groundwork has been prepared by the stakeholders listed in Annex II, within the framework of two EURATOM FP6 (Sixth Framework Programme) Coordination Actions, namely SNF-TP (Sustainable Nuclear Fission Technology Platform) and PATEROS (Partitioning and Transmutation European Road-map for Sustainable Nuclear Energy), with contributions from Europe's technical safety organisations. This vision report prepares the launch of the European Technology Platform on Sustainable Nuclear Energy (SNE-TP). It proposes a vision for the short-, medium- and long-term development of nuclear fission energy technologies, with the aim of achieving a sustainable production of nuclear energy, a significant progress in economic performance, and a continuous improvement of safety levels as well as resistance to proliferation. In particular, this document proposes road-maps for the development and deployment of potentially sustainable nuclear technologies, as well as actions to harmonize Europe's training and education, whilst renewing its research infrastructures. Public acceptance is also an important issue for the development of nuclear energy. Therefore, research in the fields of nuclear installation safety, protection of workers and populations against radiation, management of all types of waste, and governance methodologies with public participation will be promoted. The proposed road-maps provide the backbone for a strategic research agenda (SRA) to maintain

  13. Nuclear proliferation and safeguards. Summary

    International Nuclear Information System (INIS)

    1982-03-01

    This comprehensive analysis of the technological, economic, and political factors affecting the potential spread of nuclear weapons proved useful in the congressional debate which culminated in the Nuclear Non-Proliferation Act of 1978. The report was subsequently published commercially and has been a frequently cited reference in the literature on proliferation and nuclear power. Despite developments since 1977, the information in the OTA report is still useful to those wishing to obtain an indepth understanding of the issues. Included is an analysis of why a nation might want nuclear weapons development program and the various sources of nuclear material are discussed. The control of proliferation is considered as well as its relation to the nuclear industry

  14. Domestic Politics and Nuclear Proliferation

    International Nuclear Information System (INIS)

    Kim, Chul Min; Yim, Man Sung

    2016-01-01

    The external security threat is known as the most important factor of nuclear weapons program, the domestic politics situation can also affect the nuclear proliferation decision of a country. For example, when a leader wants nuclear weapons as an ultimate weapon, the domestic politics situation can determine the effectiveness of the weapons program of a country. This study analyzes the current knowledge of the relationship between domestic politics and nuclear proliferation and suggests the main challenges of the quantitative models trying to calculate nuclear proliferation risk of countries. The domestic politics status is one of the most important indicators of nuclear program. However, some variables have never been used in quantitative analyses; for example, number of veto players and the public opinion on nuclear weapons; despite they are considered to be important in various qualitative studies. Future studies should focus on how should they be coded and how can they be linked with existing domestic politics variables

  15. Domestic Politics and Nuclear Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chul Min; Yim, Man Sung [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    The external security threat is known as the most important factor of nuclear weapons program, the domestic politics situation can also affect the nuclear proliferation decision of a country. For example, when a leader wants nuclear weapons as an ultimate weapon, the domestic politics situation can determine the effectiveness of the weapons program of a country. This study analyzes the current knowledge of the relationship between domestic politics and nuclear proliferation and suggests the main challenges of the quantitative models trying to calculate nuclear proliferation risk of countries. The domestic politics status is one of the most important indicators of nuclear program. However, some variables have never been used in quantitative analyses; for example, number of veto players and the public opinion on nuclear weapons; despite they are considered to be important in various qualitative studies. Future studies should focus on how should they be coded and how can they be linked with existing domestic politics variables.

  16. Ultracentrifuge and non-proliferation

    International Nuclear Information System (INIS)

    Voortman, A.J.

    1977-01-01

    The author states that there is no meaningful difference, from the point of view of proliferation between peaceful, civil, scientific application of nuclear fission, and the use of it in nuclear weapons. The proliferation of the nuclear technology for weapons appeared and appears to be closely connected with the spread of peaceful applications of nuclear technology. In connection with this, he discusses the Ultracentrifuge plant at Almelo (Netherlands) and the supply of nuclear technology by West-Germany especially to Brazil. Further the changed American policy and the possibility of an American/Russian deal to prevent the spread of the nuclear enrichment technology is discussed

  17. Suggested non-proliferation criteria for commercial nuclear fuel cycles

    International Nuclear Information System (INIS)

    Laney, R.V.; Heubotter, P.R.

    1978-01-01

    Based on the Administration's policy to prevent nuclear weapons proliferation through diversion of fuel from commercial reactor fuel cycles, a ''benchmark'' set of nonproliferation criteria was prepared for the commercial nuclear fuel cycle. These criteria should eliminate incremental risks of proliferation beyond those inherent in the present generation of low-enriched-uranium-fueled reactors operating in a once-through mode, with internationally safeguarded storage of spent fuel. They focus on the balanced application of technical constraints consistent with the state of the technology, with minimal requirements for institutional constraints, to provide a basis for assessing the proliferation resistance of proposed fission power systems. The paper contains: (1) our perception of the nuclear energy policy and of the baseline proliferation risk accepted under this policy; (2) objectives for a reactor and fuel cycle strategy which address the technical, political, and institutional aspects of diversion and proliferation and, at the same time, satisfy the Nation's needs for efficient, timely, and economical utilization of nuclear fuel resources; (3) criteria which are responsive to these objectives and can therefore be used to screen proposed reactor and fuel cycle strategies; and (4) a rationale for these criteria

  18. Proliferating macrophages prevail in atherosclerosis.

    Science.gov (United States)

    Randolph, Gwendalyn J

    2013-09-01

    Macrophages accumulate in atherosclerotic lesions during the inflammation that is part of atherosclerosis development and progression. A new study in mice indicates that the accumulation of macrophages in atherosclerotic plaques depends on local macrophage proliferation rather than the recruitment of circulating monocytes.

  19. Nuclear Proliferation Technology Trends Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zentner, Michael D.; Coles, Garill A.; Talbert, Robert J.

    2005-10-04

    A process is underway to develop mature, integrated methodologies to address nonproliferation issues. A variety of methodologies (both qualitative and quantitative) are being considered. All have one thing in common, a need for a consistent set of proliferation related data that can be used as a basis for application. One approach to providing a basis for predicting and evaluating future proliferation events is to understand past proliferation events, that is, the different paths that have actually been taken to acquire or attempt to acquire special nuclear material. In order to provide this information, this report describing previous material acquisition activities (obtained from open source material) has been prepared. This report describes how, based on an evaluation of historical trends in nuclear technology development, conclusions can be reached concerning: (1) The length of time it takes to acquire a technology; (2) The length of time it takes for production of special nuclear material to begin; and (3) The type of approaches taken for acquiring the technology. In addition to examining time constants, the report is intended to provide information that could be used to support the use of the different non-proliferation analysis methodologies. Accordingly, each section includes: (1) Technology description; (2) Technology origin; (3) Basic theory; (4) Important components/materials; (5) Technology development; (6) Technological difficulties involved in use; (7) Changes/improvements in technology; (8) Countries that have used/attempted to use the technology; (9) Technology Information; (10) Acquisition approaches; (11) Time constants for technology development; and (12) Required Concurrent Technologies.

  20. Really sustainable?

    DEFF Research Database (Denmark)

    Hadjimichael, Maria; Hegland, Troels Jacob

    2016-01-01

    In recent years, there has been a proliferation in environmental, market-based product certification schemes. Typically, certifying bodies provide labels that assure that the products have been extracted or produced using environmentally (and sometimes socially) responsible practices. Ideally......, consumers can then make informed choices and select certified products over non-certified. We discuss the advantages as well as the limitations associated with such market-based certification systems drawing on three case studies of Marine Stewardship Council (MSC) certification: the Alaska Pollock Fishery......, the Faroe Islands' Saithe Fishery, and the Australian Northern Prawn Fishery. Based on our cases, a key indication is that incentives generated by market forces create a risk of certification schemes making questionable claims in order to increase and retain market shares. Monopolization of the concept...

  1. Evaluation of different toxicity assays applied to proliferating cells and to stratified epithelium in relation to permeability enhancement with glycocholate

    DEFF Research Database (Denmark)

    Eirheim, Heidi Ugelstad; Bundgaard, Christoffer; Nielsen, Hanne Mørck

    2004-01-01

    The purpose of the present study was to evaluate different toxicity assays for use on proliferating buccal TR146 cells and on stratified TR146 epithelium and to compare these results to the permeability enhancing effect of glycocholate (GC). Both the proliferating cells and the epithelium were...... across the epithelium concurrent with a decrease in the transepithelial electrical resistance (TEER) was also determined. The robustness of the epithelium was significantly higher than that of the proliferating cells (P...

  2. Development Proliferation Resistance Assessment Methodology for Regulation Purposes

    International Nuclear Information System (INIS)

    Ham, Taekyu; Seo, Janghoon; Lee, Nayoung; Yoo, Hosik

    2015-01-01

    More than 45 countries are considering embarking on nuclear power programs. As a result, the world's nuclear power generating capacity is projected to continue to grow by 2030. The installed total nuclear capacity in 373 GWe in 2012 would reach 435 and 722 GWe by 2030 in low and high scenario predictions, respectively. In Korea, there are 23 nuclear power plants in operation. Thirteen more plants are either under construction or are being planned for completion by 2027. In addition, there are active researches is taking place into pyroprocessing technology for use in treating spent fuel and reducing storage. Measures for analyzing PR of a nuclear energy system were derived by collecting attributes that influence PR and then were categorized into groups. Three measures were then developed by a series of processes; legal and institutional framework, material characteristics, and safeguardability. Since, the extrinsic features are more practical to evaluate when a regulatory body evaluates a system

  3. Enhancing proliferation resistance in advanced light water reactor fuel cycles

    International Nuclear Information System (INIS)

    Kazimi, M.S.; Pilat, E.E.; Driscoll, M.J.; Xu, Z.; Wang, D.; Zhao, X.

    2001-01-01

    Alternative once-through, light water reactor fuel designs are evaluated for capability to reduce the amount and quality of plutonium produced. Doubling the discharge burnup is quite effective, producing modest reductions in total plutonium and significant increases in 238 Pu whose heat generation and spontaneous neutrons complicate weapon usability. Reductions in the hydrogen to heavy metal ratio are counterproductive. Increases are helpful, but only small changes can be accommodated. Use of ThO 2 in a homogeneous mixture with UO 2 can reduce plutonium production to about 50% of that in a typical present day PWR, and in heterogeneous seed-blanket designs can reduce it to 30 to 45%. (author)

  4. British nuclear non-proliferation policy and the trident purchase

    International Nuclear Information System (INIS)

    Keohane, D.

    1984-01-01

    Since the mid-1950s, the UK has had a policy of making significant and sustained efforts to minimise the spread of nuclear arms. Unlike the global focus of its non-proliferation policy, the decision on Trident in centred upon national and perhaps regional requirements. At a time when non-nuclear countries are charging nuclear-weapon states with a grave failure to meet their obligations under Article VI of the NPT, Britain is making plans that would further increase the gap between the nuclear 'haves' and have-nots' and that indicate it expects to require nuclear arms in the next century. It would of course be unrealistic to expect a government to fully harmonise its manifold policies and unreasonable to suggest it should give absolute priority to one of its policy concerns, such as non-proliferation. But Britain is emphasising the high value it places upon the independent possession of strategic nuclear arms through its decision to purchase Trident, thus implicitly contradicting the logic underlying its non-proliferation policy. Compared to other factors, the influence of the Trident decision upon the non-proliferation regime appears very marginal, yet it is unlikely to strengthen that regime

  5. Building sustainability

    CSIR Research Space (South Africa)

    Mass Media

    2007-11-01

    Full Text Available particu- lar social environment also being awarded. If a building can be used by the community after hours, it should be awarded extra points.” School sports facilities or meeting halls in corporate buildings, are some example. Multi-purpose use..., architect and senior researcher for the CSIR’s Built Environment Unit, the integra- tion of sustainability in building design cannot begin soon enough before it is too late. He says: “Unfortunately nothing is in place in South Africa. For a start...

  6. Safeguards and non-proliferation: current challenges and the implications for Australia

    International Nuclear Information System (INIS)

    Leask, A.; Carlson, J.

    2006-01-01

    Full text: The expansion of nuclear programs raises the issue of how to ensure this does not increase the risk of nuclear weapons proliferation. The non-proliferation regime - based on the NPT and its verification mechanism, the IAEA safeguards system - has been developed to provide assurance that nuclear programs are exclusively peaceful. Although to date the non-proliferation regime has been remarkably successful, in recent years it has come under serious challenge. Nuclear proliferation is emerging as one of the major issues facing the international community. Addressing technical and institutional aspects of the non-proliferation regime - especially safeguards, but also complementary measures such as export controls, proliferation-resistant technology, and an international framework on sensitive technology - is important. But proliferation is a political problem, and ultimately the success of the non-proliferation regime depends on political resolve to uphold compliance, using incentives and if necessary sanctions. These issues are vitally important to Australia's future. Being a major uranium supplier has strengthened Australia's influence in non-proliferation and safeguards developments

  7. SIGMA: the novel approach of a new non-proliferating uranium enrichment technology

    International Nuclear Information System (INIS)

    Rivarola, M.; Florido, P.; Brasnarof, D.; Bergallo, E.

    2000-01-01

    The SIGMA concept, under development by Argentina, represents the evolution of the Uranium Enrichment Gaseous Diffusion technology, updated to face the challenge of the new economic-based and competitive world frame. The Enrichment technology has been historically considered as a highly proliferating activity in the nuclear field, and central countries limited the access of the developing countries to this technology. The SIGMA concept incorporates innovative proliferation resistant criteria at the beginning of the design process, and inherits all the non-proliferation features of the gaseous diffusion plants (GDPs). The radical new proliferation resistance approach of the SIGMA technology suggests a new kind of global control of the uranium enrichment market, where some developing countries might access an Enrichment plant without access to the technology itself. In this paper, we investigate the economy of the SIGMA plants, and the implications of this technology on the Uranium Global Market. (authors)

  8. SIGMA, the novel approach of a new non-proliferating uranium enrichment technology

    International Nuclear Information System (INIS)

    Rivarola, M.; Florido, P.; Brasnarof, D.; Bergallo, J.

    2001-01-01

    The SIGMA concept, under development by Argentina, represents the evolution of the Uranium Enrichment Gaseous Diffusion technology, updated to face the challenge of the new economic-based and competitive world frame. The Enrichment technology has been historically considered as a highly proliferating activity in the nuclear field, and central countries have limited the access of the developing countries to this technology. The SIGMA concept incorporates innovative proliferation resistant criteria at the beginning of the design process, and inherits all the non-proliferation features of the Gaseous Diffusion Plants (GDPs). The radical new proliferation resistant approach of the SIGMA technology, suggest a new kind of global control of the Uranium Enrichment Market, were some developing countries might access to an Enrichment plant without accessing to the technology itself. In this paper, we analyse the economy of the SIGMA plants, and the implications of this technology on the Uranium Global Market. (authors)

  9. Non proliferation of nuclear weapons?

    International Nuclear Information System (INIS)

    Le Guelte, Georges

    2015-10-01

    After having evoked the behaviour of nuclear countries regarding the development of nuclear weapons and uranium procurement, or nuclear programmes after the Second World War until nowadays, the author presents the non proliferation Treaty (NPT) as a construction at the service of super-powers. He comments and discusses the role of the IAEA control system and its evolutions: a control limited to declared installations, an export control with the spectre of plutonium, a control system thwarted by some technological innovations, information systems coming in, and an additional protocol related to the application of guarantees. He comments the evolution of the context from a bipolar world to a world without pole which raises the issue of how to have commitments respected: description of the role and practice of non proliferation during the Cold War, after the Cold War, and in a world without governance

  10. Supermolecular drug challenge to overcome drug resistance in cancer cells.

    Science.gov (United States)

    Onishi, Yasuhiko; Eshita, Yuki; Ji, Rui-Cheng; Kobayashi, Takashi; Onishi, Masayasu; Mizuno, Masaaki; Yoshida, Jun; Kubota, Naoji

    2018-06-04

    Overcoming multidrug resistance (MDR) of cancer cells can be accomplished using drug delivery systems in large-molecular-weight ATP-binding cassette transporters before entry into phagolysosomes and by particle-cell-surface interactions. However, these hypotheses do not address the intratumoral heterogeneity in cancer. Anti-MDR must be related to alterations of drug targets, expression of detoxification, as well as altered proliferation. In this study, it is shown that the excellent efficacy and sustainability of anti-MDR is due to a stable ES complex because of the allosteric facilities of artificial enzymes when they are used as supramolecular complexes. The allosteric effect of supermolecular drugs can be explained by the induced-fit model and can provide stable feedback control systems through the loop transfer function of the Hill equation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Nuclear power and weapons proliferation

    International Nuclear Information System (INIS)

    Greenwood, T.; Rathjens, C.W.; Ruina, J.

    1977-01-01

    The relationship between nuclear weapons development and nuclear electric power is examined. A brief description of nuclear weapons design is first given. This is then followed by a discussion of various aspects of nuclear power technology and of how they affect a nuclear weapon programme. These include fuel cycles, chemical reprocessing of spent fuel, uranium enrichment, and the control of dissemination of nuclear technology. In conclusion there is a discussion of possible political and institutional controls for limiting nuclear proliferation. (U.K.)

  12. CBRN and proliferation in Asia

    International Nuclear Information System (INIS)

    Brisset, Jean-Vincent

    2015-01-01

    The author proposes a brief overview of the history, evolution and status of military nuclear weapons and programmes as well as bacteriologic and chemical weapons (nuclear weapons, ballistic missile, and position with respect with the Conventions on chemical and bacteriologic weapons) in Asian countries (China, Japan, India, Pakistan, North Korea). In a second part, he discusses issues related to exports and possible proliferation from these countries

  13. Neural control of colonic cell proliferation.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1980-03-15

    The mitotic rate in rat colonic crypts and in dimethylhydrazine-induced colonic carcinomas was measured using a stathmokinetic technique. In sympathectomized animals cell proliferation was retarded in the crypts but not in the tumors, whereas in animals treated with Metaraminol, a drug which releases norepinephrine from nerve terminals, crypt cell but not tumor cell proliferation was accelerated. Blockade of alpha-adrenoceptors also inhibited crypt cell proliferation. However, stimulation of beta-adrenoceptors inhibited and blockade of beta-adrenoceptors accelerated tumor cell proliferation without influencing crypt cell proliferation. Injection of either serotonin or histamine stimulated tumor but not crypt cell proliferation and blockade or serotonin receptors or histamine H2-receptors inhibited tumor cell proliferation. It is postulated that cell proliferation in the colonic crypts, like that in the jejunal crypts, is under both endocrine and autonomic neural control whereas colonic tumor cell division is subject to endocrine regulation alone.

  14. Interdependences between sustainable development and sustainable economy

    OpenAIRE

    Emilia Mioara CÂMPEANU; Carmen Valentina RĂDULESCU

    2014-01-01

    Sustainable development and sustainable economy are mostly used concepts. Understanding clearly their meaning allows their use in an appropriate context and, therefore, their boundaries in terms of theoretical and practical approaches on which occasion it can be given their interdependencies. The paper aim is to analyze the interdependences between sustainable development and sustainable economy.

  15. FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells.

    Science.gov (United States)

    Bourseguin, Julie; Bonet, Caroline; Renaud, Emilie; Pandiani, Charlotte; Boncompagni, Marina; Giuliano, Sandy; Pawlikowska, Patrycja; Karmous-Benailly, Houda; Ballotti, Robert; Rosselli, Filippo; Bertolotto, Corine

    2016-11-09

    Proteins involved in genetic stability maintenance and safeguarding DNA replication act not only against cancer initiation but could also play a major role in sustaining cancer progression. Here, we report that the FANC pathway is highly expressed in metastatic melanoma harboring the oncogenic microphthalmia-associated transcription factor (MiTF). We show that MiTF downregulation in melanoma cells lowers the expression of several FANC genes and proteins. Moreover, we observe that, similarly to the consequence of MiTF downregulation, FANC pathway silencing alters proliferation, migration and senescence of human melanoma cells. We demonstrate that the FANC pathway acts downstream MiTF and establish the existence of an epistatic relationship between MiTF and the FANC pathway. Our findings point to a central role of the FANC pathway in cellular and chromosomal resistance to both DNA damage and targeted therapies in melanoma cells. Thus, the FANC pathway is a promising new therapeutic target in melanoma treatment.

  16. The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling.

    Science.gov (United States)

    Engström, Wilhelm; Darbre, Philippa; Eriksson, Staffan; Gulliver, Linda; Hultman, Tove; Karamouzis, Michalis V; Klaunig, James E; Mehta, Rekha; Moorwood, Kim; Sanderson, Thomas; Sone, Hideko; Vadgama, Pankaj; Wagemaker, Gerard; Ward, Andrew; Singh, Neetu; Al-Mulla, Fahd; Al-Temaimi, Rabeah; Amedei, Amedeo; Colacci, Anna Maria; Vaccari, Monica; Mondello, Chiara; Scovassi, A Ivana; Raju, Jayadev; Hamid, Roslida A; Memeo, Lorenzo; Forte, Stefano; Roy, Rabindra; Woodrick, Jordan; Salem, Hosni K; Ryan, Elizabeth P; Brown, Dustin G; Bisson, William H

    2015-06-01

    The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Virtual Sustainability

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2010-09-01

    Full Text Available In four ways, massively multiplayer online role-playing games may serve as tools for advancing sustainability goals, and as laboratories for developing alternatives to current social arrangements that have implications for the natural environment. First, by moving conspicuous consumption and other usually costly status competitions into virtual environments, these virtual worlds might reduce the need for physical resources. Second, they provide training that could prepare individuals to be teleworkers, and develop or demonstrate methods for using information technology to replace much transportation technology, notably in commuting. Third, virtual worlds and online games build international cooperation, even blending national cultures, thereby inching us toward not only the world consciousness needed for international agreements about the environment, but also toward non-spatial government that cuts across archaic nationalisms. Finally, realizing the potential social benefits of this new technology may urge us to reconsider a number of traditional societal institutions.

  18. Sustainability; Sustentabilidade

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter analyses the production chain of ethanol, considering the impacts on the quality of the air, water supplies, soil occupation and biodiversity, and the efforts for the soil preservation. It is pointed out the activities of the production cycle and use of bio ethanol due to great uncertainties as far the environmental impacts is concerning and that will deserve more attention in future evaluations. At same time, the chapter highlights another activities where the present acknowledge is sufficient to assure the control and/or prediction of consequences of the desired intervention on the environment media to accommodate the sugar and ethanol production expansion. The consideration is not conservative but to promote the sustainable development.

  19. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Goldston

    2010-03-03

    Integrated energy, environment and economics modeling suggests electrical energy use will increase from 2.4 TWe today to 12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources. Thus nuclear power may be needed to provide ~30% by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century proliferation risks are much greater, and more resistant to mitigation. The risks of nuclear power should be compared with the risks of the estimated 0.64oC long-term global surface-average temperature rise predicted if nuclear power were replaced with coal-fired power plants without carbon sequestration. Fusion energy, if developed, would provide a source of nuclear power with much lower proliferation risks than fission.

  20. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    International Nuclear Information System (INIS)

    Goldston, Robert J.

    2011-01-01

    Integrated energy, environment and economics modeling suggests that worldwide electrical energy use will increase from 2.4 TWe today to ∼12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources derived from natural energy flows. Thus nuclear power may be needed to provide ∼30%, 3600 GWe, by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century global nuclear proliferation risks are much greater, and more resistant to mitigation. Fusion energy, if successfully demonstrated to be economically competitive, would provide a source of nuclear power with much lower proliferation risks than fission.

  1. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    International Nuclear Information System (INIS)

    Goldston, Robert J.

    2010-01-01

    Integrated energy, environment and economics modeling suggests electrical energy use will increase from 2.4 TWe today to 12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources. Thus nuclear power may be needed to provide ∼30% by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century proliferation risks are much greater, and more resistant to mitigation. The risks of nuclear power should be compared with the risks of the estimated 0.64 C long-term global surface-average temperature rise predicted if nuclear power were replaced with coal-fired power plants without carbon sequestration. Fusion energy, if developed, would provide a source of nuclear power with much lower proliferation risks than fission.

  2. Climate Change, Nuclear Power and Nuclear Proliferation: Magnitude Matters

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Goldston

    2011-04-28

    Integrated energy, environment and economics modeling suggests that worldwide electrical energy use will increase from 2.4 TWe today to ~12 TWe in 2100. It will be challenging to provide 40% of this electrical power from combustion with carbon sequestration, as it will be challenging to provide 30% from renewable energy sources derived from natural energy flows. Thus nuclear power may be needed to provide ~30%, 3600 GWe, by 2100. Calculations of the associated stocks and flows of uranium, plutonium and minor actinides indicate that the proliferation risks at mid-century, using current light-water reactor technology, are daunting. There are institutional arrangements that may be able to provide an acceptable level of risk mitigation, but they will be difficult to implement. If a transition is begun to fast-spectrum reactors at mid-century, without a dramatic change in the proliferation risks of such systems, at the end of the century global nuclear proliferation risks are much greater, and more resistant to mitigation. Fusion energy, if successfully demonstrated to be economically competitive, would provide a source of nuclear power with much lower proliferation risks than fission.

  3. Sustainability Science Needs Sustainable Data!

    Science.gov (United States)

    Downs, R. R.; Chen, R. S.

    2013-12-01

    Sustainability science (SS) is an 'emerging field of research dealing with the interactions between natural and social systems, and with how those interactions affect the challenge of sustainability: meeting the needs of present and future generations while substantially reducing poverty and conserving the planet's life support systems' (Kates, 2011; Clark, 2007). Bettencourt & Kaur (2011) identified more than 20,000 scientific papers published on SS topics since the 1980s with more than 35,000 distinct authors. They estimated that the field is currently growing exponentially, with the number of authors doubling approximately every 8 years. These scholars are undoubtedly using and generating a vast quantity and variety of data and information for both SS research and applications. Unfortunately we know little about what data the SS community is actually using, and whether or not the data that SS scholars generate are being preserved for future use. Moreover, since much SS research is conducted by cross-disciplinary, multi-institutional teams, often scattered around the world, there could well be increased risks of data loss, reduced data quality, inadequate documentation, and poor long-term access and usability. Capabilities and processes therefore need to be established today to support continual, reliable, and efficient preservation of and access to SS data in the future, especially so that they can be reused in conjunction with future data and for new studies not conceived in the original data collection activities. Today's long-term data stewardship challenges include establishing sustainable data governance to facilitate continuing management, selecting data to ensure that limited resources are focused on high priority SS data holdings, securing sufficient rights to allow unforeseen uses, and preparing data to enable use by future communities whose specific research and information needs are not yet known. Adopting sustainable models for archival

  4. Structure, conduct, and sustainability of the international low-enriched fuel fabrication industry

    International Nuclear Information System (INIS)

    Rothwell, Geoffrey

    2008-01-01

    This paper examines the cost structures of fabricating Low-Enriched Uranium fuel (LEU, enriched to 5% enrichment) light water reactor fuels. The LEU industry is decades old, and (except for high entry cost, i.e., the cost of designing and licensing a fuel fabrication facility and its fuel), labor and additional fabrication lines can be added by industry incumbents at Nth-of-a-Kind cost to the maximum capacity allowed by the license. On the other hand, new entrants face higher First-of-a-Kind costs and high new-facility licensing costs, increasing the scale required for entry thus discouraging small scale entry by countries with only a few nuclear power plants. Therefore, the industry appears to be competitive with sustainable investment in fuel-cycle states, and structural barriers-to-entry increase its proliferation resistance. (author)

  5. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    International Nuclear Information System (INIS)

    Rodriguez-Acebes, Sara; Cueva, Paloma de la; Ferruelo, Antonio J.; Fernandez-Hernando, Carlos; Lasuncion, Miguel A.; Martinez-Botas, Javier; Gomez-Coronado, Diego

    2008-01-01

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 μM lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  6. Dose-dependent dual effects of cholesterol and desmosterol on J774 macrophage proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Acebes, Sara [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Cueva, Paloma de la; Ferruelo, Antonio J; Fernandez-Hernando, Carlos [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); Lasuncion, Miguel A [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Departamento de Bioquimica y Biologia Molecular, Universidad de Alcala, Alcala de Henares (Spain); Martinez-Botas, Javier [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain); Gomez-Coronado, Diego [Servicio de Bioquimica-Investigacion, Hospital Ramon y Cajal, Carretera de Colmenar, km 9, 28034 Madrid (Spain); CIBER de Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid (Spain)], E-mail: diego.gomez@hrc.es

    2008-12-12

    We addressed the ability of native, oxidized and acetylated low-density lipoproteins (nLDL, oxLDL and acLDL, respectively) and desmosterol to act as sources of sterol for the proliferation of J774A.1 macrophages. Treatment with 0.5 {mu}M lovastatin and lipoprotein-deficient serum suppressed cell proliferation. This inhibition was effectively prevented by nLDL, but only to a lesser extent by oxLDL. AcLDL, despite its ability to deliver a higher amount of cholesterol to J774 macrophages than the other LDLs, was dependent on mevalonate supply to sustain cell proliferation. Similarly, exogenous desmosterol, which is not converted into cholesterol in J774 cells, required the simultaneous addition of mevalonate to support optimal cell growth. Expression of hydroxymethyl glutaryl coenzyme A reductase mRNA was potently down-regulated by acLDL and exogenous desmosterol, but the effect was weaker with other sterol sources. We conclude that nLDL is more efficient than modified LDL in sustaining macrophage proliferation. Despite the requirement of cholesterol or desmosterol for J774 cell proliferation, excessive provision of either sterol limits mevalonate availability, thus suppressing cell proliferation.

  7. Overview of DOE-NE Proliferation and Terrorism Risk Assessment

    International Nuclear Information System (INIS)

    Sadasivan, Pratap

    2012-01-01

    Research objectives are: (1) Develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of current reactors; (2) Develop improvements in the affordability of new reactors to enable nuclear energy; (3) Develop Sustainable Nuclear Fuel Cycles; and (4) Understand and minimize the risks of nuclear proliferation and terrorism. The goal is to enable the use of risk information to inform NE R and D program planning. The PTRA program supports DOE-NE's goal of using risk information to inform R and D program planning. The FY12 PTRA program is focused on terrorism risk. The program includes a mix of innovative methods that support the general practice of risk assessments, and selected applications.

  8. The European dimension in non-proliferation

    International Nuclear Information System (INIS)

    Krause, J.

    1996-01-01

    Europe was for decades the focal point of efforts to prevent or constrain nuclear proliferation and the first region in which non-proliferation efforts failed. Paper deals with current proliferation problems in Europe, namely, diversion of weapons, diversion from dismantling, production over-capacity, security concerns. Legal instruments against proliferation in Europe described here include development of international norms; instruments of security assurance and cooperation; disarmament assistance; fissile material management; assistance in creating export control systems; improving and harmonizing export controls for dual-purpose items. Problems in implementing non-proliferation instruments are described separately

  9. Distinct roles of the receptor tyrosine kinases c-ErbB and c-Kit in regulating the balance between erythroid cell proliferation and differentiation

    NARCIS (Netherlands)

    Wessely, O.; Mellitzer, G.; von Lindern, M.; Levitzki, A.; Gazit, A.; Ischenko, I.; Hayman, M. J.; Beug, H.

    1997-01-01

    In the bone marrow, multipotent and committed hematopoietic progenitors have to closely regulate their balance between sustained proliferation without differentiation (self renewal) and entering a terminal differentiation pathway. A useful model to analyze this regulation at the molecular level is

  10. Nanoparticles for cells proliferation enhancement

    International Nuclear Information System (INIS)

    Popa, V.; Braniste, F.; Tiginyanu, I.M.; Lisii, C.; Nacu, V.

    2013-01-01

    The potential of semiconductor nanoparticles as stimulator for avian mesenchyme stem cells proliferation enhancement is demonstrated. The effect is related to nanoparticles polarization due to external ultrasound field resulting in local electrical stimulation. Our preliminary results demonstrates that the number of cells have been increased by 23 % ±2%) in cell cultures under the action of external ultrasound stimulation. Morphological analysis and viability shows no differences between the control group and the group studied. These results suggest the possibility for tissue regeneration enhancement by remote stimulation of implanted semiconductor nanoparticles. (authors)

  11. The USA and proliferation in Northeast Asia

    International Nuclear Information System (INIS)

    Weeks, S.B.

    1995-01-01

    United States policy on proliferation in Northeast Asia poses a test of balance between general US global non-proliferation goals and specific US regional security goals for Northeast Asia. US policy on proliferation in Northeast Asia further poses a test of priorities for US bilateral relations with the key Northeast Asian states, as non-proliferation and regional security goals must be weighed against other (e.g., economic, human rights) declared US policy goals. The result is a US policy equation for Northeast Asia proliferation that is considerably more complex in execution than might be expected from the simple statement of the US goal to avoid nuclear proliferation in Northeast Asia. The question of security assurances - both negative and positive - may be closely related to US policies to avoid proliferation in Northeast Asia

  12. Using proliferation assessment methodologies for Safeguards-by-Design

    International Nuclear Information System (INIS)

    Van der Meer, K.; Rossa, R.; Turcanu, C.; Borella, A.

    2013-01-01

    MYRRHA, an accelerator driven system (ADS) is designed as a proton accelerator coupled to a liquid Pb-Bi spallation target, surrounded by a Pb-Bi cooled sub-critical neutron multiplying medium in a pool type configuration. An assessment based on three methodologies was made of the proliferation risks of the MYRRHA ADS in comparison with the BR2 MTR, an existing research reactor at the Belgian Nuclear Research Centre SCK-CEN. The used methodologies were the TOPS (Technical Opportunities to Increase the Proliferation Resistance of Nuclear Power Systems), the PR-PP and the INPRO methodologies. The various features of the methodologies are described and the results of the assessments are given and discussed. It is concluded that it would be useful to define one single methodology with two options to perform a quick and a more detailed assessment. The paper is followed by the slides of the presentation

  13. Non-proliferation and disarmament

    International Nuclear Information System (INIS)

    Ritter von Wagner, A.

    1993-01-01

    In 1995 the Conference on the prolongation of the Non-Proliferation Treaty will take place. Will it be extended for a long term, indefinitely or only for a fixed period? The Federal Government of Germany advocates an unlimited extension of the Non-Proliferation Treaty. Others have different ideas alleging that the Treaty is imperfect and discriminating. It is a thorn in the side of many States, in particular of the Third World, which no longer want to put up with being treated as second-class states. One argument which is considered especially embarrassing by developing countries as a visible expression of such discrimination, are the nuclear tests which are still carried out by nuclear weapon states. Is the political situation still such that one needs those weapons? Strategists gradually find it difficult to argument; over and over again they claim that an abandonment of nuclear weapons would make the world unsafer. But development has gradually passed over them. Nevertheless, one finds it hard to throw overboard considerations which for years have determined one's thinking. (orig./HSCH) [de

  14. Gas Centrifuges and Nuclear Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Albright, David

    2004-09-15

    Gas centrifuges have been an ideal enrichment method for a wide variety of countries. Many countries have built gas centrifuges to make enriched uranium for peaceful nuclear purposes. Other countries have secretly sought centrifuges to make highly enriched uranium for nuclear weapons. In more recent times, several countries have secretly sought or built gas centrifuges in regions of tension. The main countries that have been of interest in the last two decades have been Pakistan, Iraq, Iran, and North Korea. Currently, most attention is focused on Iran, Pakistan, and North Korea. These states did not have the indigenous abilities to make gas centrifuges, focusing instead on illicit and questionable foreign procurement. The presentation covered the following main sections: Spread of centrifuges through illicit procurement; Role of export controls in stopping proliferation; Increasing the transparency of gas centrifuge programs in non-nuclear weapon states; and, Verified dismantlement of gas centrifuge programs. Gas centrifuges are important providers of low enriched uranium for civil nuclear power reactors. They also pose special nuclear proliferation risks. We all have special responsibilities to prevent the spread of gas centrifuges into regions of tension and to mitigate the consequences of their spread into the Middle East, South Asia, and North Asia.

  15. Stress Resistance in the Naked Mole-Rat: The Bare Essentials – A Mini-Review

    Science.gov (United States)

    Lewis, Kaitlyn N.; Mele, James; Hornsby, Peter J.; Buffenstein, Rochelle

    2012-01-01

    Background Studies comparing similar-sized species with disparate longevity may elucidate novel mechanisms that abrogate aging and prolong good health. We focus on the longest living rodent, the naked mole-rat. This mouse-sized mammal lives ∼8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to spontaneous neoplasia but also shows minimal decline in age-associated physiological traits. Objectives We assess the current status of stress resistance and longevity, focusing in particular on the molecular and cellular responses to cytotoxins and other stressors between the short-lived laboratory mouse and the naked mole-rat. Results Like other experimental animal models of lifespan extension, naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing LD50 values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins. Conclusion Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and

  16. Stress resistance in the naked mole-rat: the bare essentials - a mini-review.

    Science.gov (United States)

    Lewis, Kaitlyn N; Mele, James; Hornsby, Peter J; Buffenstein, Rochelle

    2012-01-01

    Studies comparing similar-sized species with disparate longevity may elucidate novel mechanisms that abrogate aging and prolong good health. We focus on the longest living rodent, the naked mole-rat. This mouse-sized mammal lives ~8 times longer than do mice and, despite high levels of oxidative damage evident at a young age, it is not only very resistant to spontaneous neoplasia but also shows minimal decline in age-associated physiological traits. We assess the current status of stress resistance and longevity, focusing in particular on the molecular and cellular responses to cytotoxins and other stressors between the short-lived laboratory mouse and the naked mole-rat. Like other experimental animal models of lifespan extension, naked mole-rat fibroblasts are extremely tolerant of a broad spectrum of cytotoxins including heat, heavy metals, DNA-damaging agents and xenobiotics, showing LD(50) values between 2- and 20-fold greater than those of fibroblasts of shorter-lived mice. Our new data reveal that naked mole-rat fibroblasts stop proliferating even at low doses of toxin whereas those mouse fibroblasts that survive treatment rapidly re-enter the cell cycle and may proliferate with DNA damage. Naked mole-rat fibroblasts also show significantly higher constitutive levels of both p53 and Nrf2 protein levels and activity, and this increases even further in response to toxins. Enhanced cell signaling via p53 and Nrf2 protects cells against proliferating with damage, augments clearance of damaged proteins and organelles and facilitates the maintenance of both genomic and protein integrity. These pathways collectively regulate a myriad of mechanisms which may contribute to the attenuated aging profile and sustained healthspan of the naked mole-rat. Understanding how these are regulated may be also integral to sustaining positive human healthspan well into old age and may elucidate novel therapeutics for delaying the onset and progression of physiological declines

  17. Sustainable NREL - Site Sustainability Plan FY 2015

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-01-01

    NREL's Site Sustainability Plan FY 2015 reports on sustainability plans for the lab for the year 2015 based on Executive Order Goals and provides the status on planned actions cited in the FY 2014 report.

  18. Sustainability : Politics and governance

    NARCIS (Netherlands)

    Heinrichs, Harald; Biermann, Frank

    2016-01-01

    he article gives an overview of global sustainability policy and politics. It is shown how international policy making on sustainable development has progressed from environmental policy toward recent approaches of Earth system governance. Key challenges of international sustainability politics are

  19. Sustainability in Transport Planning

    DEFF Research Database (Denmark)

    Gudmundsson, Henrik; Greve, Carsten

    Contribution to session J: Joint University Sustainability Initiatives. This session will provide an inspiring overview of interdisciplinary research and teaching activities on sustainability bridging DTU, KU, and CBS, and introduce the joint collaboration Copenhagen Sustainability Initiative (COSI...

  20. Textiles and clothing sustainability sustainable technologies

    CERN Document Server

    2017-01-01

    This is the first book to deal with the innovative technologies in the field of textiles and clothing sustainability. It details a number of sustainable and innovative technologies and highlights their implications in the clothing sector. There are currently various measures to achieve sustainability in the textiles and the clothing industry, including innovations in the manufacturing stage, which is the crux of this book.

  1. Sustainable diets within sustainable food systems.

    Science.gov (United States)

    Meybeck, Alexandre; Gitz, Vincent

    2017-02-01

    Sustainable diets and sustainable food systems are increasingly explored by diverse scientific disciplines. They are also recognised by the international community and called upon to orient action towards the eradication of hunger and malnutrition and the fulfilment of sustainable development goals. The aim of the present paper is to briefly consider some of the links between these two notions in order to facilitate the operationalisation of the concept of sustainable diet. The concept of sustainable diet was defined in 2010 combining two totally different perspectives: a nutrition perspective, focused on individuals, and a global sustainability perspective, in all its dimensions: environmental, economic and social. The nutrition perspective can be easily related to health outcomes. The global sustainability perspective is more difficult to analyse directly. We propose that it be measured as the contribution of a diet to the sustainability of food systems. Such an approach, covering the three dimensions of sustainability, enables identification of interactions and interrelations between food systems and diets. It provides opportunities to find levers of change towards sustainability. Diets are both the results and the drivers of food systems. The drivers of change for those variously involved, consumers and private individuals, are different, and can be triggered by different dimensions (heath, environment, social and cultural). Combining different dimensions and reasons for change can help facilitate the transition to sustainable diets, recognising the food system's specificities. The adoption of sustainable diets can be facilitated and enabled by food systems, and by appropriate policies and incentives.

  2. Missile proliferation and missile defense

    International Nuclear Information System (INIS)

    Zarif, M. Javad

    2002-01-01

    The global security environment is becoming increasingly volatile and dangerous. A new arms race is looming in the horizon ... [Missiles have] become the strong weapon of the poor and the discriminated against who find themselves vulnerable to outside threat. They believe missiles may prove instrumental in deterring the enemy from beginning a full scale war ... the engagement of all states at the United Nations in the issue of missiles, through the panel of governmental experts, and the new idea of exploring the subject in the Conference on Disarmament do provide a dim light at the end of the tunnel. ... Efforts at non-proliferation of missiles are more likely to succeed when viewed as an integral part of a global and comprehensive negotiation and progress in other areas of disarmament. (author)

  3. Romania non-proliferation policy

    International Nuclear Information System (INIS)

    Biro, Lucian; Grama, Viviana

    2001-01-01

    Full text: Non-proliferation concept in Romania is based on the Treaty on the Non-proliferation of Nuclear Weapons, which was ratified in 1970. According to the Article III of the Treaty, Romania ratified in 1972, the Agreement between Romania and IAEA for the application of Safeguards in connection with the Treaty on the Non-proliferation of Nuclear Weapons. In 2000 Romania ratified the Additional Protocol to contribute through increased transparency, to confidence that no undeclared nuclear activities are concealed within the declared programme or make use of elements of that programme. Under the Additional Protocol Romania understands to increase the transparency of its nuclear activities lengthways fuel cycle. Romania has a strong legal framework to control nuclear material and nuclear activities. The Law 111/1996, republished is the Law on the safe deployment of nuclear activities. CNCAN issued National Regulations for Safeguards and Physical Protection. Prospecting for uranium in Romania was initiated in 1950. Between 1962 and 1978 all the uranium ore production was stockpiled at the mine sites. In 1978 the Feldioara Powder Plant was commissioned, since then both ore stockpiles and ore exploited have been processed to uranium chemical concentrates. The Powder Plant Feldioara was conceived and built following the necessity of milling and processing the uranium ore to UO 2 , in concordance with the national nuclear programme in order to produce electric energy from nuclear fuel. The Nuclear Fuel Plant has capability to manufacture CANDU-6 nuclear fuel. Nuclear Fuel Plant consists of two Production areas, the Quality Assurance and Engineering Departments. There are two Production Departments: Pelleting area including granulation, pressing, sintering, pellet grinding, uranium recycling and Assembling area including components fabrication, beryllium coating, brazing, graphite coating, fuel element and bundle assembly welding. Romania's Strategy for Energy Sector

  4. China's position on nuclear non-proliferation

    International Nuclear Information System (INIS)

    Qian Jiadong.

    1986-01-01

    The paper discusses China's position on nuclear non-proliferation, in view of the fact that China does not subscribe to the Non-Proliferation Treaty (NPT). China refuses to accede to the NPT because it considers the treaty to be discriminatory, and reasons are given for this point of view. However its stand for nuclear disarmament and disapproval of nuclear proliferation are declared. Nuclear arms race, prevention of nuclear war, and nuclear disarmament are also considered. (UK)

  5. Nuclear power and nuclear-weapons proliferation

    International Nuclear Information System (INIS)

    Moniz, E.J.; Neff, T.L.

    1978-01-01

    Concern over the risk of nuclear proliferation has led to extensive reexamination of the technical, economic, and political assumptions underlying both national and international nuclear policies. An attempt is made in the present article to clarify the basic technical and political issues. The connections between various fuel cycles and their possible proliferation risks are discussed. As the resolution of the existing differing views on proliferation risks will be largely a political process, solutions to the problem are not proposed

  6. Nuclear energy and nuclear weapons proliferation

    International Nuclear Information System (INIS)

    1989-01-01

    A summary of the report dispatched in the middle of 1978 by the Atlantic Council of United States, organized by North American citizens, is presented. The report considers the relation between the production of nucleoelectric energy and the capacity of proliferation of nuclear weapons. The factors which affect the grade of proliferation risk represented by the use of nuclear energy in the world comparing this risk with the proliferation risks independently of nuclear energy, are examined. (M.C.K.) [pt

  7. MARKOV Model Application to Proliferation Risk Reduction of an Advanced Nuclear System

    International Nuclear Information System (INIS)

    Bari, R.A.

    2008-01-01

    The Generation IV International Forum (GIF) emphasizes proliferation resistance and physical protection (PR and PP) as a main goal for future nuclear energy systems. The GIF PR and PP Working Group has developed a methodology for the evaluation of these systems. As an application of the methodology, Markov model has been developed for the evaluation of proliferation resistance and is demonstrated for a hypothetical Example Sodium Fast Reactor (ESFR) system. This paper presents the case of diversion by the facility owner/operator to obtain material that could be used in a nuclear weapon. The Markov model is applied to evaluate material diversion strategies. The following features of the Markov model are presented here: (1) An effective detection rate has been introduced to account for the implementation of multiple safeguards approaches at a given strategic point; (2) Technical failure to divert material is modeled as intrinsic barriers related to the design of the facility or the properties of the material in the facility; and (3) Concealment to defeat or degrade the performance of safeguards is recognized in the Markov model. Three proliferation risk measures are calculated directly by the Markov model: the detection probability, technical failure probability, and proliferation time. The material type is indicated by an index that is based on the quality of material diverted. Sensitivity cases have been done to demonstrate the effects of different modeling features on the measures of proliferation resistance

  8. Sustaining Shipments

    Energy Technology Data Exchange (ETDEWEB)

    Bonnardel-Azzarelli, Betty [World Nuclear Transport Institute, Remo House, 4th Floor, 310-312 Regent Street, London, London W1B 3AX (United Kingdom)

    2009-06-15

    Transport plays an essential role in bringing the benefits of the atom to people the world over. Each day thousands of shipments of radioactive materials are transported on national and international routes. These consignments are essential to many aspects of modern life, from the generation of electricity, to medicine and health, scientific research and agriculture. Maintaining safe, cost-effective transport is essential to support them. Despite an outstanding safety record spanning over 45 years, the transport of radioactive materials cannot and must not be taken for granted. In an era of nuclear expansion, with increased transports required to more destinations, a worrisome trend for global supply is that some shipping companies, air carriers, ports and terminals, have instituted policies of not accepting radioactive materials. Experience has shown that the reasons for delays and denials of shipments are manifold and often have their origin in mis-perceptions about the nature of the materials and the requirements for their safe handling and carriage. There is growing recognition internationally of the problems created by shipment delays and denials and they now are being addressed in a more proactive way by such organisations as the International Atomic Energy Agency (IAEA). The rapidly changing supply-demand equation for fuel cycle services: substantial new nuclear build planned or underway in several countries, twenty-first century 'gold rush' fever in uranium exploration and mining, proposed new mechanisms to assure fuel supply to more countries while minimising proliferation risks. But, can supply to meet demand be assured, unless and until transport can be assured? And is it reasonable to expect that transport can be assured to meet the emerging demand-side of the fuel cycle equation when industry already is facing increased instances of shipment delays and denials? It is a worrisome trend for global supply of Class 7 radioactive materials that

  9. Security environment and nuclear proliferation problems in East Asia

    International Nuclear Information System (INIS)

    Suh, Mark Byung-Moon

    1997-01-01

    East Asia was and still is divided into two conflicting ideological blocs. Because of the Cold War between these two blocs, two international wars were fought and tensions limited interactions among these countries. Despite these political constraints, in recent years East Asia has become economically one of the most dynamic regions in the world. Now that the Cold War between the USA and the Soviet Union is over, the danger of global nuclear war involving the nuclear powers in the region has been practically eliminated. Nonetheless, security has become more complex and demands a whole new set of arrangements. Yet the region lacks a cohesive multilateral framework for conflict resolution, and only recently have various attempts been made to create a political forum for the countries in the region. The problem and the danger of nuclear proliferation was vividly shown by the North Korean nuclear crisis in the last years. This issue not only halted the fragile process of normalization between the two Koreas, which started in 1988, but almost led to a new military conflict on the peninsula involving the two Koreas and the USA. It was defused only after the USA proved willing to offer security guarantees to North Korea. This problem still needs to be resolved, and it demands radical changes in the overall political environment in the region. Needless to say, proliferation in North Korea would have entailed grave consequences for the security of the region as well as for the international non-proliferation regime. This paper reviews the issue of nuclear proliferation of the three non-nuclear states in the region and deals with the non-introduction of nuclear weapons in the region by the nuclear powers. It discusses the prospects for a nuclear-weapon-free zone on the Korean peninsula. Perspectives of a sustainable security environment in East Asia will be briefly discussed

  10. The handbook of nuclear non-proliferation

    International Nuclear Information System (INIS)

    Yang, M. H.; Lee, B. W.; Oh, K. B.; Lee, H. M.; Ko, H. S.; Ryu, J. S.; Lee, K. S.

    2003-07-01

    This report analyzed international non-proliferation regime preventing from spread of nuclear weapon. This report took review from the historical background of non-proliferation regime to the recent changes and current status. It is here divided into multilateral and bilateral regime. First of all, this report dealt four multilateral treaties concluded for international non-proliferation such as NPT, NWFZ, CTBT and others. And international organization and regimes concerned with non-proliferation are also analyzed focused on UN, IAEA, ZC and NSG, regional safeguards system and international conferences. In addition, this report reviewed the nuclear cooperation agreement related with Korea which is a important tool for bilateral regime

  11. Intelligence and Nuclear Proliferation: Lessons Learned

    International Nuclear Information System (INIS)

    Hansen, Keith A.

    2011-09-01

    Intelligence agencies play a fundamental role in the prevention of nuclear proliferation, as they help to understand other countries' intentions and assess their technical capabilities and the nature of their nuclear activities. The challenges in this area remain, however, formidable. Past experiences and the discoveries of Iraq's WMD programs, of North Korean nuclear weapon program, and of Iranian activities, have put into question the ability of intelligence to monitor small, clandestine proliferation activities from either states or non-state entities. This Proliferation Paper analyzes the complex challenges intelligence faces and the various roles it plays in supporting national and international nuclear non-proliferation efforts, and reviews its track record. In an effort to shed light on the role and contribution of intelligence in national and international efforts to halt, if not prevent, further nuclear weapon proliferation, this paper first analyzes the challenges intelligence faces in monitoring small, clandestine proliferation activities and the role it plays in supporting non-proliferation efforts. It then reviews the intelligence track record in monitoring proliferation including the lessons learned from Iraq. Finally, it addresses whether it is possible for intelligence to accurately monitor future clandestine proliferation efforts. (author)

  12. Sustainability and the anthropogenic alteration of evolutionary processes

    Directory of Open Access Journals (Sweden)

    John Cairns, Jr.

    2004-08-01

    Full Text Available Persuasive evidence indicates that Earth is now experiencing a major biotic crisis. Even if humankind ceases severe stress on natural systems, the crisis will probably disrupt the basic evolutionary processes that characterized the period preceding the agricultural and industrial revolutions.Proliferation of drug and pesticide resistant species and opportunistic species that thrive in human-dominated ecosystems will become increasingly common. The effect on humankind of altering basic evolutionary processes is uncertain because the understanding of these processes is not robust. The probable result will not be an environment as favorable to humans as the one that has existed for most of human history. Humans probably have altered the environment since Homo sapiens first appeared. However, only in the last two centuries has the degree and rate of change reached levels now considered by many people to be ‘normal’, even though the record shows they are not.Greatly improved technology has facilitated increased exploitation of natural resources to unsustainablelevels. This exploitation, in turn, has led to exponential human population growth, which has depleted natural capital (living systems and the services they provide. Economic globalization has ensured that ecosystems far distant from consumers can be and are profitably exploited. Economicgrowth has become a universal mantra that is coupled with a conviction that such growth can continue indefinitely on a finite planet. A major paradigm shift is essential if sustainable use of the planet is to become a reality.

  13. Sustained Spheromak Physics Experiment, SSPX

    International Nuclear Information System (INIS)

    Hooper, E.B.

    1997-01-01

    The Sustained Spheromak Physics Experiment is proposed for experimental studies of spheromak confinement issues in a controlled way: in steady state relative to the confinement timescale and at low collisionality. Experiments in a flux - conserver will provide data on transport in the presence of resistive modes in shear-stabilized systems and establish operating regimes which pave the way for true steady-state experiments with the equilibrium field supplied by external coils. The proposal is based on analysis of past experiments, including the achievement of T e = 400 eV in a decaying spheromak in CTX. Electrostatic helicity injection from a coaxial ''''gun'''' into a shaped flux conserver will form and sustain the plasma for several milliseconds. The flux conserver minimizes fluxline intersection with the walls and provides MHD stability. Improvements from previous experiments include modem wall conditioning (especially boronization), a divertor for density and impurity control, and a bias magnetic flux for configurational flexibility. The bias flux will provide innovative experimental opportunities, including testing helicity drive on the large-radius plasma boundary. Diagnostics include Thomson scattering for T e measurements and ultra-short pulse reflectrometry to measure density and magnetic field profiles and turbulence. We expect to operate at T e of several hundred eV, allowing improved understanding of energy and current transport due to resistive MHD turbulence during sustained operation. This will provide an exciting advance in spheromak physics and a firm basis for future experiments in the fusion regime

  14. Improved Technology To Prevent Nuclear Proliferation And Counter Nuclear Terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, J; Yuldashev, B; Labov, S; Knapp, R

    2006-06-12

    As the world moves into the 21st century, the possibility of greater reliance on nuclear energy will impose additional technical requirements to prevent proliferation. In addition to proliferation resistant reactors, a careful examination of the various possible fuel cycles from cradle to grave will provide additional technical and nonproliferation challenges in the areas of conversion, enrichment, transportation, recycling and waste disposal. Radiation detection technology and information management have a prominent role in any future global regime for nonproliferation. As nuclear energy and hence nuclear materials become an increasingly global phenomenon, using local technologies and capabilities facilitate incorporation of enhanced monitoring and detection on the regional level. Radiation detection technologies are an important tool in the prevention of proliferation and countering radiological/nuclear terrorism. A variety of new developments have enabled enhanced performance in terms of energy resolution, spatial resolution, passive detection, predictive modeling and simulation, active interrogation, and ease of operation and deployment in the field. For example, various gamma ray imaging approaches are being explored to combine spatial resolution with background suppression in order to enhance sensitivity many-fold at reasonable standoff distances and acquisition times. New materials and approaches are being developed in order to provide adequate energy resolution in field use without the necessity for liquid nitrogen. Different detection algorithms enable fissile materials to be distinguished from other radioisotopes.

  15. Proliferation of Schwann cells induced by axolemmal and myelin membranes

    International Nuclear Information System (INIS)

    Dinneen, M.

    1985-01-01

    Purified Schwann Cells were cultured from neonatal rat sciatic nerve using a modification of the method of Brockes. Schwann cells and contaminating fibroblasts were unambiguously identified using fluorescent antibodies of 2'3' cyclic nucleotide 3'-phosphodiesterase and the thy 1.1 antigen respectively. The Schwann cells were quiescent unless challenged with mitogens. They proliferated rapidly in response to the soluble mitogen, cholera toxin, or to membrane fractions from rat CNS or PNS, prepared by the method of DeVries. Mitogenic activity was present in both axolemmal and myelin enriched fractions and promoted a 10-15 fold increase in the rate of 3 H-thymidine uptake. The axolemmal mitogen was sensitive to heat (80 0 C for 10 minutes), trypsin digestion (0.05% x 30 mins) or to treatment with endoglycosidase D, suggesting that it could be a glycoprotein. Fifty percent of the axolemmal mitogenic activity was solubilized in 1% octyl-glucoside. The solubilized material, however, was very unstable and further purification was not possible. The myelin associated mitogenic activity was markedly different. It was resistant to freeze thaw cycles, trypsin digestion of endoglycosidase treatment and the activity was actually enhanced by heating at 100 0 C for two hours. It is proposed that the axolemmal activity is responsible for Schwann cell proliferation during development and that the myelin associated activity promotes Schwann cell proliferation during Wallerian degeneration

  16. Brexit, Euratom and nuclear proliferation

    International Nuclear Information System (INIS)

    Soedersten, Anna

    2016-01-01

    One of the issues absent from the academic (and public) debate on the United Kingdom's (UK) referendum vote to withdraw from the European Union (EU) (commonly referred to as 'Brexit') is what will happen to the UK's membership in the European Atomic Energy Community (Euratom). The Euratom Treaty was signed in Rome in 1957, together with the European Economic Community (EEC) Treaty. It was concluded for an unlimited period and it establishes a Community that has a separate legal personality from the EU. Thus, the EU and Euratom form two separate, although closely linked entities. Euratom's principal mission is related to the economy, tasked with 'creating the conditions necessary for the speedy establishment and growth of nuclear industries'; in other words, to promote the nuclear industry. This reflects the high expectations for nuclear energy in the 1950's. Some even believed that the development of nuclear energy would trigger an industrial revolution; however, Euratom only came to play a minor role in the European integration process. Despite this, the Euratom Treaty has remained, almost unchanged, since its adoption and is still frequently applied, although it is unclear to what extent it has boosted the nuclear industry. This article has a two-fold purpose. The first purpose is to address the constitutional issue of 'partial membership'. All EU member states are also members of Euratom. It has always been assumed that with membership in the EU also comes a membership in Euratom. But, what about withdrawal? What are the arguments for 'partial membership'? The second purpose of this article is to shed light on some implications of Brexit as it relates to Euratom. The most serious consequences are perhaps found in the area of nuclear non-proliferation. The United Kingdom is one of two nuclear weapon states in the EU (France being the other one). Withdrawal from Euratom means withdrawal from its control system, the system of so-called nuclear safeguards. Under

  17. Assessing sustainable remediation frameworks using sustainability principles.

    Science.gov (United States)

    Ridsdale, D Reanne; Noble, Bram F

    2016-12-15

    The remediation industry has grown exponentially in recent decades. International organizations of practitioners and remediation experts have developed several frameworks for integrating sustainability into remediation projects; however, there has been limited attention to how sustainability is approached and operationalized in sustainable remediation frameworks and practices - or whether sustainability plays any meaningful role at all in sustainable remediation. This paper examines how sustainability is represented in remediation frameworks and the guidance provided for practical application. Seven broad sustainability principles and review criteria are proposed and applied to a sample of six international remediation frameworks. Not all review criteria were equally satisfied and none of the frameworks fully met all criteria; however, the best performing frameworks were those identified as sustainability remediation frameworks. Intra-generational equity was addressed by all frameworks. Integrating social, economic and biophysical components beyond triple-bottom-line indicators was explicitly addressed only by the sustainable remediation frameworks. No frameworks provided principle- or rule-based guidance for dealing with trade-offs in sustainability decisions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Sustainable development and nuclear power

    International Nuclear Information System (INIS)

    1997-11-01

    Although there is an awareness on both the technical and political levels of the advantages of nuclear power, it is not a globally favoured option in a sustainable energy future. A sizeable sector of public opinion remains hesitant or opposed to its increased use, some even to a continuation at present levels. With various groups calling for a role for nuclear power, there is a need openly and objectively to discuss the concerns that limit its acceptance: the perceived health effects, the consequences of severe accidents, the disposal of high level waste and nuclear proliferation. This brochure discusses these concerns, and also the distinct advantages of nuclear power. Extensive comparisons with other energy sources are made

  19. Sustainable development and nuclear power

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    Although there is an awareness on both the technical and political levels of the advantages of nuclear power, it is not a globally favoured option in a sustainable energy future. A sizeable sector of public opinion remains hesitant or opposed to its increased use, some even to a continuation at present levels. With various groups calling for a role for nuclear power, there is a need openly and objectively to discuss the concerns that limit its acceptance: the perceived health effects, the consequences of severe accidents, the disposal of high level waste and nuclear proliferation. This brochure discusses these concerns, and also the distinct advantages of nuclear power. Extensive comparisons with other energy sources are made. Figs, tabs.

  20. Proliferation after the Iraq war; La proliferation apres la guerre d'Irak

    Energy Technology Data Exchange (ETDEWEB)

    Daguzan, J.F

    2004-09-15

    This article uses the Iraq war major event to analyze the approach used by the US to fight against proliferation. It questions the decision and analysis process which has led to the US-British intervention and analyzes the consequences of the war on the proliferation of other countries and on the expected perspectives. Finally, the future of proliferation itself is questioned: do we have to fear more threat or is the virtuous circle of non-proliferation well started? (J.S.)

  1. Technology and sustainability

    NARCIS (Netherlands)

    Kroeze, C.; Boersema, J.J.; Tellegen, E.; Cremers, A.

    2011-01-01

    In ten essays, this book addresses a broad range of issues related to the interplay of sustainability and technology. How do population growth and technology relate to sustainable development? Can globalization be reconciled with sustainable development? Is sustainability a subjective or an

  2. Sustainable consumption and marketing

    NARCIS (Netherlands)

    Dam, van Y.K.

    2016-01-01

    Sustainable development in global food markets is hindered by the discrepancy between positive consumer attitudes towards sustainable development or sustainability and the lack of corresponding sustainable consumption by a majority of consumers. Apparently for many (light user) consumers the

  3. Externality or sustainability economics?

    International Nuclear Information System (INIS)

    Bergh, Jeroen C.J.M. van den

    2010-01-01

    In an effort to develop 'sustainability economics' Baumgaertner and Quaas (2010) neglect the central concept of environmental economics-'environmental externality'. This note proposes a possible connection between the concepts of environmental externality and sustainability. In addition, attention is asked for other aspects of 'sustainability economics', namely the distinction weak/strong sustainability, spatial sustainability and sustainable trade, distinctive sustainability policy, and the ideas of early 'sustainability economists'. I argue that both sustainability and externalities reflect a systems perspective and propose that effective sustainability solutions require that more attention is given to system feedbacks, notably other-regarding preferences and social interactions, and energy and environmental rebound. The case of climate change and policy is used to illustrate particular statements. As a conclusion, a list of 20 insights and suggestions for research is offered. (author)

  4. The challenges of nuclear proliferation

    International Nuclear Information System (INIS)

    Le Guelte, Georges

    2015-01-01

    The author of this article first outlines that the Non Proliferation Treaty (NPT) is a tool of domination used by nuclear powers: they can keep and even develop their own nuclear arsenal, while other countries who sign this treaty commit themselves not to try to acquire nuclear weapons. The USA and USSR kept on persuading various countries to sign this treaty, but eventually let some countries develop their military nuclear programme (Israel, Pakistan, or India). He evokes technical difficulties in the application of the Treaty, notably for the control of centrifugation activities. He outlines that the USA have now a dominant position with respect to this Treaty and its application, but that the Treaty remains a major safety element for the world. He evokes more recent and negative evolutions: the withdrawal of North Korea from the Treaty, the destruction of an Iraqi nuclear reactor by Israel (i.e. the destruction of a nuclear installation belonging to a country who signed the NPT by a country who did not sign it). He proposes an overview of the Iranian issue (history of the Iranian nuclear programme, of the nuclear crisis, of the still going on negotiations), and describes what could be the worst possible scenario

  5. North Korea: a mercenary proliferator?

    International Nuclear Information System (INIS)

    Hemez, Remy

    2015-01-01

    After having recalled that North Korea possesses a rather advanced ballistic programme which has been started in the 1970 with the Chinese support, that North Korea is the fourth world producer of ballistic missiles, the author outlines that this country has become a major proliferator as it exports this production to different States and non-State actors. He recalls the long history of relationships between North Korea and terrorist organisations (even during the Cold War), comments the current and major support of North Korea to Hamas and Hezbollah in Gaza and in Lebanon. These relationships are then related with those these both organisations have with Syria and Iran who are in fact the relays between them and North Korea. The author explains why Hamas and Hezbollah must buy their weapons to such a far country: Iran is submitted to international sanctions, Iran and Syria want to avoid being banned from the international community for selling weapon to a terrorist (or so-said) organisation, and prices are rather competitive. If North Korea is also submitted to international sanctions, weapon smuggling seems to be institutional in this country. The author finally briefly evokes the issue of chemical weapons: North Korea possesses few thousand tonnes of these weapons, and could export them to non-state organisations

  6. Director`s series on proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, K.C.; Price, M.E. [eds.

    1995-11-17

    This is an occasional publication of essays on the topics of nuclear, chemical, biological, and missile proliferation. The views represented are those of the author`s. Essay topics include: Nuclear Proliferation: Myth and Reality; Problems of Enforcing Compliance with Arms Control Agreements; The Unreliability of the Russian Officer Corps: Reluctant Domestic Warriors; and Russia`s Nuclear Legacy.

  7. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  8. Engineering Sustainability: A Technical Approach to Sustainability

    OpenAIRE

    Rosen, Marc A.

    2012-01-01

    Sustainability is a critically important goal for human activity and development. Sustainability in the area of engineering is of great importance to any plans for overall sustainability given 1) the pervasiveness of engineering activities in societies, 2) their importance in economic development and living standards, and 3) the significant impacts that engineering processes and systems have had, and continue to have, on the environment. Many factors that need to be considered and appropriate...

  9. Use of elicitors as an approach for sustainable agriculture

    African Journals Online (AJOL)

    Yomi

    2010-12-29

    Dec 29, 2010 ... elicitors act in cellular defense mechanism of crops, to improve protection and management for sustainable ... mechanisms governing resistance to plant diseases and therefore could ..... Emerging MAP kinase pathways in ...

  10. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through

  11. The modular pebble bed nuclear reactor - the preferred new sustainable energy source for electricity, hydrogen and potable water production?

    International Nuclear Information System (INIS)

    Kemeny, L.G.

    2003-01-01

    This paper describes a joint project of Massachusetts Institute of technology, Nu-Tec Inc. and Proto Power. The elegant simplicity of graphite moderated pebble bed reactor is the basis for the 'generation four' nuclear power plants. High Temperature Gas Cooled (HTGC) nuclear power plant have the potential to become the preferred base load sustainable energy source for the new millennium. The great attraction of these helium cooled 'Generation Four' nuclear plant can be summarised as follows: Factory assembly line production; Modularity and ease of delivery to site; High temperature Brayton Cycle ideally suited for cogeneration of electricity, potable water and hydrogen; Capital and operating costs competitive with hydrocarbon plant; Design is inherently meltdown proof and proliferation resistant

  12. International Conference on Fast Reactors and Related Fuel Cycles: Safe Technologies and Sustainable Scenarios (FR13). Presentations

    International Nuclear Information System (INIS)

    2013-01-01

    The conference, which was held from 4 to 7 of March 2013 in Paris, provided a forum to exchange information on national and international programmes, and more generally new developments and experience, in the field of fast reactors and related fuel cycle technologies. A first goal was to identify and discuss strategic and technical options that have been proposed by individual countries or companies. Another goal was to promote the development of fast reactors and related fuel cycle technologies in a safe, proliferation resistant and economic way. A third goal was to identify gaps and key issues that need to be addressed in relation to the industrial deployment of fast reactors with a closed fuel cycle. A fourth goal was to engage young scientists and engineers in this field, in particular with sustainability, innovation, simulation, safety, economics and public acceptance

  13. Use of Molecular Imaging Markers of Glycolysis, Hypoxia and Proliferation (18F-FDG, 64Cu-ATSM and 18F-FLT) in a Dog with Fibrosarcoma

    DEFF Research Database (Denmark)

    Zornhagen, Kamilla; Clausen, Malene; Hansen, Anders Elias

    2015-01-01

    Glycolysis, hypoxia, and proliferation are important factors in the tumor microenvironment contributing to treatment-resistant aggressiveness. Imaging these factors using combined functional positron emission tomography and computed tomography can potentially guide diagnosis and management...

  14. The non-proliferation experiment

    Energy Technology Data Exchange (ETDEWEB)

    Hannon, W.J. [Lawrence Livermore National Lab., CA (United States)

    1994-12-31

    On September 22, 1993, the Department of Energy detonated more than 1.2 million kg of blasting agent in a tunnel in Rainier Mesa at the Nevada Test Site. The resulting explosion generated seismic, electromagnetic, and air pressure signals that were recorded on instruments deployed at distances ranging from a few meters to hundreds and, in some cases, thousands of kilometers. More than 12 organizations made measurements before, during, and after the explosions. The explosion and its associated experiments are known as the Non-Proliferation Experiment (NPE). Analyses of the measurements made during the NPE and comparisons with similar measurements made on previous nearly nuclear explosions and on a co-located smaller explosion detonated at the same site are providing basic phenomenological insights into what is potentially one of the comprehensive Test Ban Treaty (CTBT)-distinguishing between nuclear explosions and some of the many conventional explosions that occur each year. The NPE is also providing information on the use of chemical explosions to develop empirical discriminants in regions where no nuclear explosions have been recorded. In another verification application, several NPE projects are examining the utility of on-site, pre-shot, shot-time, and post-shot measurements of gas seepage, seismic activity, and other observables as a means of identifying the source of signals that appear like nuclear explosions at regional distances. Two related activities are being considered. First, challenge on-site inspections, conducted after an event has occurred, may be able to use the characteristics of phenomena that persist after the explosion to detect and identify the source of the signals that appeared ambiguous or explosion-like to remote sensors. Second, cooperative, on-site measurements made at the time of a pre-nounced conventional explosion may provide assurance that a nuclear explosion did not occur as part of or in place of the pre-announced explosion.

  15. Sustainability in Business

    DEFF Research Database (Denmark)

    Tollin, Karin; Vej, Jesper

    2012-01-01

    How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level of market...... managers' mindsets, a framework addressing sustainability from four organisational learning schools was designed and followed......How do companies integrate sustainability into their strategy and practices, and what factors explain their approach? In this paper a typology of sustainability strategies is presented as well as a conceptual framework relating sustainability at the company level to the functional level...... of marketing. The central contribution of the typology is a strategic and managerial view on sustainability. Furthermore, the typology shows that sustainability in business is enacted from different areas of competences and fields in the literature (e.g. supply chain management, corporate branding, value...

  16. Progesterone resistance in endometriosis

    DEFF Research Database (Denmark)

    Patel, Bansari G; Rudnicki, Martin; Yu, Jie

    2017-01-01

    Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women...... with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment...... renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone resistant state...

  17. Nuclear proliferation: prospects, problems, and proposals

    International Nuclear Information System (INIS)

    Anon.

    1977-01-01

    This issue of the ANNALS addresses itself to three aspects of nuclear proliferation: the prospect that new nuclear powers will come on the scene, the problems that their arrival may create, and ways of coping with those problems. In an introductory paper, ''Quo Vadimus,'' Joseph I. Coffey investigates the pros and cons of proliferation, concluding that it is not a question of whether there will be nuclear proliferation, but in what countries. Part I, Where We Are, contains five papers preceded by introductory comments by Joseph I. Coffey. The papers and their authors are: Why States Go--and Don't Go--Nuclear, William Epstein; How States Can ''Go Nuclear,'' Frank C. Barnaby; What Happens If. . .Terrorists, Revolutionaries, and Nuclear Weapons, David Kreiger; Safeguards Against Diversion of Nuclear Material: An Overview, Ryukichi Imai; and Reducing the Incentives to Proliferation, George H. Quester. Part II, And Where We May Go, again includes some introductory remarks by Joseph I. Coffey. The seven succeeding papers are: Nth Powers of the Future, Ashok Kapur; Nuclear Proliferation and World Politics, Lewis A. Dunn; Arms Control in a Nuclear Armed World, Colin Gray; The United Nations, the Superpowers, and Proliferation, Abraham Bargman; Proliferation and the Future: Destruction or Transformation, Frederick C. Thayer; Decision Making in a Nuclear Armed World, Michael Brenner; and The United States in a World of Nuclear Powers, Michael Nacht. This special report is concluded with a glossary

  18. Which future for nuclear counter-proliferation?

    International Nuclear Information System (INIS)

    Duval, M.

    2010-01-01

    Dealing with the case of nuclear weapons possessed by nuclear states (but not eventually by terrorists), the author first identifies the constants of counter-proliferation: it is linked to interest conflicts between those who try to preserve their monopoly and those who try to acquire a new weapon either because of a threat or for reasons of regional prestige, the evolution from use to deterrence, the appearance of new actors after the USA and Russia, the role of nuclear tactical weapons, and the future of Russian weapons and know-how. He presents the international counter-proliferation context: the Non Proliferation Treaty (NPT), the IAEA and its controls, the Nuclear Supplier Group (NSG), the nuclear-free zones, the Comprehensive Test Ban Treaty (CTBT), the Missile Technology Control Regime (MTCR). He describes how and why proliferation occurs: uranium enrichment and plutonium technology, political reasons in different parts of the world. Then, he gives an overview of the proliferation status by commenting the cases of Israel, Iraq, India, Pakistan, North Korea, and Iran. He discusses the future of proliferation (involved countries, existence of a nuclear black market) and of counter-proliferation as far as Middle-East and North Korea are concerned. He tries finally to anticipate the consequences for nuclear deterrence strategy, and more particularly for Europe and France

  19. Harmine stimulates proliferation of human neural progenitors

    Directory of Open Access Journals (Sweden)

    Vanja Dakic

    2016-12-01

    Full Text Available Harmine is the β-carboline alkaloid with the highest concentration in the psychotropic plant decoction Ayahuasca. In rodents, classical antidepressants reverse the symptoms of depression by stimulating neuronal proliferation. It has been shown that Ayahuasca presents antidepressant effects in patients with depressive disorder. In the present study, we investigated the effects of harmine in cell cultures containing human neural progenitor cells (hNPCs, 97% nestin-positive derived from pluripotent stem cells. After 4 days of treatment, the pool of proliferating hNPCs increased by 71.5%. Harmine has been reported as a potent inhibitor of the dual specificity tyrosine-phosphorylation-regulated kinase (DYRK1A, which regulates cell proliferation and brain development. We tested the effect of analogs of harmine, an inhibitor of DYRK1A (INDY, and an irreversible selective inhibitor of monoamine oxidase (MAO but not DYRK1A (pargyline. INDY but not pargyline induced proliferation of hNPCs similarly to harmine, suggesting that inhibition of DYRK1A is a possible mechanism to explain harmine effects upon the proliferation of hNPCs. Our findings show that harmine enhances proliferation of hNPCs and suggest that inhibition of DYRK1A may explain its effects upon proliferation in vitro and antidepressant effects in vivo.

  20. Sustainable Table | Welcome to Sustainable Table

    Science.gov (United States)

    Sustainable Seafood Industrial Agriculture Industrial Livestock Production Antibiotics Hormones rBGH Animal , safeguarding animal welfare and supporting local communities. Questions to Ask Asking questions is the best way Livestock Husbandry Sustainable Crop Production Innovative Agriculture New Farmers Organic Agriculture Local

  1. Cell proliferation in rat nasal respiratory epithelium following three months exposure to formaldehyde gas

    International Nuclear Information System (INIS)

    Monticello, T.M.; Morgan, K.T.

    1990-01-01

    Formaldehyde (HCHO), a ubiquitous chemical and rat nasal carcinogen, enhances cell proliferation in rat, monkey, and xenotransplanted human respiratory epithelium following short-term exposure. The present studies were designed to evaluate cell proliferation in relation to tumor induction in rat nasal respiratory epithelium following subchronic HCHO exposure. Male F-344 rats were whole-body exposed to either 0, 0.7, 2, 6, 10, or 15 ppm HCHO, for wither 4 d (6hr/d), 6 wks (5d/wk) or 3 months. Animals were labeled with tritiated thymidine prior to euthanasia. Nasal sections were processed for autoradiography and cell proliferation data was expressed as unit length labeling indices (ULLI). HCHO-induced lesions and increases in cell proliferation occurred in specific regions of the nose, primarily the wall of the lateral meatus and nasal septum of the anterior nasal cavity. Following 4 d exposure, significant elevations in cell proliferation were observed only in the 6, 10 and 15 ppm groups (16-, 18-, and 20-fold increase over control, respectively). Increases in ULLI were also present in the 6, 10 and 15 ppm groups after 6 wks of exposure (12-, 35-, and 40-fold increase over control). However, after 3 months exposure, elevations in ULLI were present only in the 10 and 15 ppm groups (9- and 14-fold increase over controls). These results demonstrate that (1) low levels of HCHO (0.7 and 2 ppm) do not increase cell proliferation in rat nasal respiratory epithelium; (2) 6 ppm HCHO induces transient increases in cell proliferation; and (3) clearly carcinogenic concentrations of HCHO (10 and 15 ppm) cause sustained elevations in cell proliferation which may play an important role in HCHO-induced carcinogenesis

  2. Education for sustainable development

    DEFF Research Database (Denmark)

    Breiting, Søren

    2009-01-01

     An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related ...... to the use of natural resources and other matters, and how that kind of issues can be dealt with in education as ESD....... An introduction to the idea of sustainable development (SD) and education for sustainable development (ESD) with reference to the international Decade for Education for Sustainable Development . The chapter includes a focus on conflicting interests between present and future generations related...

  3. Smart Sustainable Islands VS Smart Sustainable Cities

    Science.gov (United States)

    Pantazis, D. N.; Moussas, V. C.; Murgante, B.; Daverona, A. C.; Stratakis, P.; Vlissidis, N.; Kavadias, A.; Economou, D.; Santimpantakis, K.; Karathanasis, B.; Kyriakopoulou, V.; Gadolou, E.

    2017-09-01

    This paper has several aims: a) the presentation of a critical analysis of the terms "smart sustainable cities" and "smart sustainable islands" b) the presentation of a number of principles towards to the development methodological framework of concepts and actions, in a form of a manual and actions guide, for the smartification and sustainability of islands. This kind of master plan is divided in thematic sectors (key factors) which concern the insular municipalities c) the creation of an island's smartification and sustainability index d) the first steps towards the creation of a portal for the presentation of our smartification actions manual, together with relative resources, smart applications examples, and, in the near future the first results of our index application in a number of Greek islands and e) the presentation of some proposals of possible actions towards their sustainable development and smartification for the municipalities - islands of Paros and Antiparos in Greece, as case studies.

  4. Sustainability indicators for the assessment of nuclear power

    International Nuclear Information System (INIS)

    Stamford, Laurence; Azapagic, Adisa

    2011-01-01

    Electricity supplies an increasing share of the world's total energy demand and that contribution is set to increase. At the same time, there is increasing socio-political will to mitigate impacts of climate change as well as to improve energy security. This, in combination with the desire to ensure social and economic prosperity, creates a pressing need to consider the sustainability implications of future electricity generation. However, approaches to sustainability assessment differ greatly in their scope and methodology as currently there is no standardised approach. With this in mind, this paper reviews sustainability indicators that have previously been used to assess energy options and proposes a new sustainability assessment methodology based on a life cycle approach. In total, 43 indicators are proposed, addressing the techno-economic, environmental and social sustainability issues associated with energy systems. The framework has been developed primarily to address concerns associated with nuclear power in the UK, but is applicable to other energy technologies as well as to other countries. -- Highlights: → New framework for life cycle sustainability assessment of nuclear power developed. → The framework comprises 43 indicators addressing techno-economic, environmental and social sustainability. → Completely new indicators developed to address different sustainability issues, including nuclear proliferation, energy supply diversity and intergenerational equity. → The framework enables sustainability comparisons of nuclear and other electricity technologies. → Indicators can be used by various stakeholders, including industry, policy makers and NGOs to help identify more sustainable electricity options.

  5. Non-proliferation and multinational enterprises

    International Nuclear Information System (INIS)

    1979-04-01

    The paper supplements CC/WG.2/9 in presenting the Japanese delegation's contribution in the areas of non-proliferation and multi-national enterprises. The paper questions whether multinational enrichment enterprises would constitute a significant non-proliferation factor, noting that the nature of the venture might create a potential for the dissemination of sensitive information. The paper also argues that a multi-national venture which was not economically competitive (with national facilities) would have questionable viability. The conclusion is that non-proliferation advantages, if any, would be a result, not an objective of such a venture

  6. Conceptualising sustainability assessment

    International Nuclear Information System (INIS)

    Pope, Jenny; Annandale, David; Morrison-Saunders, Angus

    2004-01-01

    Sustainability assessment is being increasingly viewed as an important tool to aid in the shift towards sustainability. However, this is a new and evolving concept and there remain very few examples of effective sustainability assessment processes implemented anywhere in the world. Sustainability assessment is often described as a process by which the implications of an initiative on sustainability are evaluated, where the initiative can be a proposed or existing policy, plan, programme, project, piece of legislation, or a current practice or activity. However, this generic definition covers a broad range of different processes, many of which have been described in the literature as 'sustainability assessment'. This article seeks to provide some clarification by reflecting on the different approaches described in the literature as being forms of sustainability assessment, and evaluating them in terms of their potential contributions to sustainability. Many of these are actually examples of 'integrated assessment', derived from environmental impact assessment (EIA) and strategic environmental assessment (SEA), but which have been extended to incorporate social and economic considerations as well as environmental ones, reflecting a 'triple bottom line' (TBL) approach to sustainability. These integrated assessment processes typically either seek to minimise 'unsustainability', or to achieve TBL objectives. Both aims may, or may not, result in sustainable practice. We present an alternative conception of sustainability assessment, with the more ambitious aim of seeking to determine whether or not an initiative is actually sustainable. We term such processes 'assessment for sustainability'. 'Assessment for sustainability' firstly requires that the concept of sustainability be well-defined. The article compares TBL approaches and principles-based approaches to developing such sustainability criteria, concluding that the latter are more appropriate, since they avoid many

  7. Handbook of sustainable engineering

    CERN Document Server

    Lee, Kun-Mo

    2013-01-01

    "The efficient utilization of energy, sustainable use of natural resources, and large-scale adoption of sustainable technologies is the key to a sustainable future. The Handbook of Sustainable Engineering provides tools that will help us achieve these goals". Nobel Prize Winner Dr. R.K. Pauchauri, Chairman, UN Intergovernmental Panel on Climate Change As global society confronts the challenges of diminishing resources, ecological degradation, and climate change, engineers play a crucial role designing and building technologies and products that fulfil our needs for utility and sustainability. The Handbook of Sustainable Engineering equips readers with the context and the best practices derived from both academic research and practical examples of successful implementations of sustainable technical solutions. The handbook’s content revolves around the two themes, new ways of thinking and new business models, including sustainable production, products, service systems and consumption while addressing key asse...

  8. Sustainable Water Infrastructure

    Science.gov (United States)

    Resources for state and local environmental and public health officials, and water, infrastructure and utility professionals to learn about sustainable water infrastructure, sustainable water and energy practices, and their role.

  9. Sustainable development. First part

    International Nuclear Information System (INIS)

    Colombo, U.; Lanzavecchia, G.; Berrini, M; Zambrini, M.; Bologna, G.; Carraro, C.; Hinterberger, F.; Mastino, G.; Federico, A.; Gaudioso, D.; Luise, A.; Mauro, F.; Padovani, L.; Federico, A.

    1998-01-01

    This paper summarizes a collective effort and represents the second edition of: Environment, energy, economy: a sustainable future. In this work are reported various interventions on sustainable development problem [it

  10. Sustainable Public Bids

    Directory of Open Access Journals (Sweden)

    Gil César Costa de Paula

    2016-06-01

    Full Text Available In this article we will discuss the issue of sustainability in public procurement, given that the government in Brazil is constituted as a great promoter of economic development and needs to adapt its acquisitions worldwide sustainability agenda.

  11. Neighbourhood facilities for sustainability

    CSIR Research Space (South Africa)

    Gibberd, Jeremy T

    2013-01-01

    Full Text Available . In this paper these are referred to as ‘Neighbourhood Facilities for Sustainability’. Neighbourhood Facilities for Sustainability (NFS) are initiatives undertaken by individuals and communities to build local sustainable systems which not only improve...

  12. FORUM: Is Ecotourism Sustainable?

    Science.gov (United States)

    Wall

    1997-07-01

    / It is legitimate to ask whether and in what form tourism might contribute to sustainable development. This is not the same as sustainable tourism which, as a single-sector approach to development, may overlook important linkages with other sectors. If tourism is to contribute to sustainable development, then it must be economically viable, ecologically sensitive and culturally appropriate. Ecotourism is often advocated as being a sustainable form of tourism but imprecision in terminology clouds basic issues and there are strong economic, ecological, and cultural reasons for believing that, even in its purest forms, ecotourism is likely to present substantial challenges to destination areas, particularly if it competes for scarce resources and displaces existing uses and users. Sustainable tourism and ecotourism are not synonyms, many forms of ecotourism may not be sustainable, and if ecotourism is to contribute to sustainable development, then careful planning and management will be required.KEY WORDS: Ecotourism; Sustainable development; Development; Tourism

  13. Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation

    International Nuclear Information System (INIS)

    Diaz-Gomez, Luis; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Silva, Maite; Dominguez, Fernando; Sheikh, Faheem A.; Cantu, Travis; Desai, Raj; Garcia, Vanessa L.; Macossay, Javier

    2014-01-01

    Biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds were coated with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP was obtained from human buffy coat, and tested on human adipose-derived mesenchymal stem cells (MSCs) to confirm cell proliferation and cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via lyophilization, which resulted in a uniform sponge-like coating of 2.85 (S.D. 0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties (Young's modulus, tensile stress and tensile strain), sustained release of total protein and growth factors (PDGF-BB, TGF-β1 and VEGF), and hemocompatibility. MSC seeded on the PRP–PCL nanofibers showed an increased adhesion and proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled angiogenesis features observed as neovascularization in a chicken chorioallantoic membrane (CAM) model. Overall, these results suggest that PRP–PCL scaffolds hold promise for tissue regeneration applications. - Highlights: • Platelet-rich plasma (PRP) can be adsorbed on electrospun fibers via lyophilization. • PRP coating enhanced mesenchymal stem cell adhesion and proliferation on scaffolds. • PRP-coated scaffolds showed sustained release of growth factors. • Adsorbed PRP provided angiogenic features. • PRP-poly(ε-caprolactone) scaffolds hold promise for tissue regeneration applications

  14. Biodegradable electrospun nanofibers coated with platelet-rich plasma for cell adhesion and proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Diaz-Gomez, Luis [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Alvarez-Lorenzo, Carmen, E-mail: carmen.alvarez.lorenzo@usc.es [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Concheiro, Angel [Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Silva, Maite [Instituto de Ortopedia y Banco de Tejidos Musculoesqueléticos, Universidad de Santiago de Compostela, 15872 Santiago de Compostela (Spain); Dominguez, Fernando [Fundación Publica Galega de Medicina Xenómica, Santiago de Compostela (Spain); Sheikh, Faheem A.; Cantu, Travis; Desai, Raj; Garcia, Vanessa L. [Department of Chemistry, University of Texas Pan American, Edinburg, TX 78541 (United States); Macossay, Javier, E-mail: jmacossay@utpa.edu [Department of Chemistry, University of Texas Pan American, Edinburg, TX 78541 (United States)

    2014-07-01

    Biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds were coated with platelet-rich plasma (PRP) to improve cell adhesion and proliferation. PRP was obtained from human buffy coat, and tested on human adipose-derived mesenchymal stem cells (MSCs) to confirm cell proliferation and cytocompatibility. Then, PRP was adsorbed on the PCL scaffolds via lyophilization, which resulted in a uniform sponge-like coating of 2.85 (S.D. 0.14) mg/mg. The scaffolds were evaluated regarding mechanical properties (Young's modulus, tensile stress and tensile strain), sustained release of total protein and growth factors (PDGF-BB, TGF-β1 and VEGF), and hemocompatibility. MSC seeded on the PRP–PCL nanofibers showed an increased adhesion and proliferation compared to pristine PCL fibers. Moreover, the adsorbed PRP enabled angiogenesis features observed as neovascularization in a chicken chorioallantoic membrane (CAM) model. Overall, these results suggest that PRP–PCL scaffolds hold promise for tissue regeneration applications. - Highlights: • Platelet-rich plasma (PRP) can be adsorbed on electrospun fibers via lyophilization. • PRP coating enhanced mesenchymal stem cell adhesion and proliferation on scaffolds. • PRP-coated scaffolds showed sustained release of growth factors. • Adsorbed PRP provided angiogenic features. • PRP-poly(ε-caprolactone) scaffolds hold promise for tissue regeneration applications.

  15. Institutional arrangements for the reduction of proliferation risks. Formulation, evaluation, and implementation of institutional concepts

    International Nuclear Information System (INIS)

    Kratzer, M.B.; Wonder, E.F.; Gray, J.E.; Shantzis, S.B.; Sievering, N.F.; Paige, H.W.; Jones, B.M.

    1979-12-01

    The purpose of this study was to: (1) identify alternative institutional arrangements applicable to the sensitive steps in the back-end of the fuel cycle that might reduce their associated proliferation risks; and (2) assess their advantages and disadvantages from the standpoint of nonproliferation effectiveness and political, economic, and operational acceptability. The concept of international or multinational custody of sensitive materials and facilities was found to offer a high degree of proliferation resistance and to likely be more acceptable to prospective participants than other institutional arrangements that intrude upon proprietary areas, such as facility ownership and management

  16. Institutional arrangements for the reduction of proliferation risks formulation, evaluation, and implementation of institutional concepts

    International Nuclear Information System (INIS)

    Kratzer, M.B.; Wonder, E.F.; Gray, J.E.; Shantzis, S.B.; Sievering, N.F.; Paige, H.W.; Jones, B.M.

    1979-12-01

    The purpose of this study was to: (1) identify alternative institutional arrangements applicable to the sensitive steps in the back-end of the fuel cycle that might reduce their associated proliferation risks; and (2) assess their advantages and disadvantages from the standpoint of nonproliferation effectiveness and political, economic, and operational acceptability. The concept of international or multinational custody of sensitive materials and facilities was found to offer a high degree of proliferation resistance and to likely be more acceptable to prospective participants than other institutional arrangements that intrude upon proprietary areas, such as facility ownership and management

  17. Institutional arrangements for the reduction of proliferation risks formulation, evaluation, and implementation of institutional concepts

    Energy Technology Data Exchange (ETDEWEB)

    Kratzer, M.B.; Wonder, E.F.; Gray, J.E.; Shantzis, S.B.; Sievering, N.F.; Paige, H.W.; Jones, B.M.

    1979-12-01

    The purpose of this study was to: (1) identify alternative institutional arrangements applicable to the sensitive steps in the back-end of the fuel cycle that might reduce their associated proliferation risks; and (2) assess their advantages and disadvantages from the standpoint of nonproliferation effectiveness and political, economic, and operational acceptability. The concept of international or multinational custody of sensitive materials and facilities was found to offer a high degree of proliferation resistance and to likely be more acceptable to prospective participants than other institutional arrangements that intrude upon proprietary areas, such as facility ownership and management.

  18. Canada's nuclear non-proliferation policy

    International Nuclear Information System (INIS)

    1982-05-01

    Canada's non-proliferation safeguards policy has two objectives: 1) to promote a more effective and comprehensive international non-proliferation regime; and 2) to ensure that Canadian nuclear exports will not be used for any nuclear explosive purpose. By emphasizing the key role of the Non-Proliferation Treaty, promoting reliance upon and improvements in the IAEA safeguards system, treating nuclear weapon and non-weapon states alike, and working for new approaches covering reprocessing, Canada promotes attainment of the first objective. The second is served through the network of bilateral nuclear agreements that Canada has put into place with its partners. The Canadian objective in post-INFCE forums is to persuade the international community to devise a more effective and comprehensive non-proliferation regime into which Canada and other suppliers may subsume their national requirements

  19. Handbook for nuclear non-proliferation

    International Nuclear Information System (INIS)

    Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok.

    1997-05-01

    This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs

  20. Nuclear experts and nuclear weapons proliferation

    International Nuclear Information System (INIS)

    Mueller, H.

    1979-01-01

    In Germany the issue of nuclear weapons proliferation has attracted scant attention. Most potential nuclear weapon states are important trade partners of the FRG and, since further proliferation of nuclear weapons could worsen conflicts involving these, it should be in the FRG's interest to limit proliferation. The security of the FRG is also dependent on the common interest of the great powers to avoid nuclear war. The contradictory positions of Usa and the USSR on nuclear weapons policy regarding themselves and non-nuclear weapon states encourages less developed countries to see nuclear weaponry as useful. The NPT and IAEA safeguards have only limited inhibiting effect. The nuclear export policy of the FRG has been dominated by short term economic advantage, neglecting the negative long term effects of decreased political stability. The FRG should formulate a policy based on self-restraint, positive stimuli and extension of controls, using its economic strength to deter proliferation. (JIW)

  1. Handbook for nuclear non-proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Wook; Oh, Keun Bae; Lee, Kwang Seok; Lee, Dong Jin; Ko, Han Seok

    1997-05-01

    This book analyzed international non-proliferation regime preventing from spread of nuclear weapon. This book took review from the historical background of non-proliferation regime to the recent changes and status. The regime, here, is divided into multilateral and bilateral regime. First of all, this book reports four multilateral treaties concluded for non-proliferation such as NPT, NWFZ, CTBT and others. Secondly, international organization and regimes concerned with non-proliferation are analyzed with emphasis of UN, IAEA, ZC and NSG, Regional Safeguards System and international conference. Finally, this book report the current circumstances of nuclear cooperation agreement related with Korea which is an important means for bilateral regime. (author). 13 tabs., 2 figs.

  2. The future of non-proliferation

    International Nuclear Information System (INIS)

    Gere, F.

    2000-01-01

    This paper comprises two parts. The first part makes a status of the non-proliferation policy: problems of ratification of Start 2 and CTBT treaties, nuclear tests in India and Pakistan in May 1998 etc. The second part makes a prospective reflexion on the evolution of the position of nuclearized countries at the 2015-2030 vista: role of Asia, nuclear perception, evolution of the US perception of non-proliferation, military strategy and European unification. (J.S.)

  3. Nuclear power and the proliferation issue

    International Nuclear Information System (INIS)

    Marshall, W.

    1978-02-01

    The purpose of the lecture is to discuss nuclear proliferation, analyse which problems are real and which are a misapprehension, and to suggest a way forward which retains the benefits of nuclear power while providing a more certain protection against undesirable proliferation. After an introductory section the lecture continues under the following headings: plutonium production and accessibility; the use of plutonium; fast reactor fuel; the interim period; conclusions. (U.K.)

  4. Panel on nuclear export and proliferation

    International Nuclear Information System (INIS)

    Kimel, W.R.

    1977-01-01

    Summaries of six panelists' remarks make the following points: one cannot suppress nuclear weapons by suppressing nuclear power; a proliferated world would be extremely dangerous; US supports IAEA safeguards; plutonium shouldn't be recycled in power reactors; and the problem of nonproliferation is a social and institutional problem, not a technological one. Viewographs showing the semantics of proliferation, ways to get nuclear weapons materials, etc. are included

  5. Russia and proliferation in Northeast Asia

    International Nuclear Information System (INIS)

    Ignatov, A.I.

    1995-01-01

    For Russia, security, including non-proliferation, in Northeast Asia means in particular the maintenance of stability. Progress in arms control and non-proliferation may enhance regional stability. A common regional approach is proposed. Russia recognizes the US alliances with Japan and republic of Korea and is searching for a new cooperation framework in the region, namely further development of relations with China and reasonable rapprochement with Japan

  6. Sustainability Statement and Policy

    Science.gov (United States)

    Journal of Education for Sustainable Development, 2009

    2009-01-01

    This article presents nine resources that focus on environmental education and sustainability. These include: (1) "Sustainability Statement and Policy," Dalhousie University, Nova Scotia, Canada, 2009, which is available at http://office.sustainability.dal.ca/Governance; (2) "Climate Literacy: The Essential Principles of Climate…

  7. The sustainable development

    International Nuclear Information System (INIS)

    2004-01-01

    In the framework of the sustainable development week (june 2003), Actu Environnement published a complete document on the sustainable development to inform the public, recall the main steps of this notion (Rio conference and the following conferences) and the possible employments. It presents also the main organizations acting in the sustainable development domain. (A.L.B.)

  8. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2017-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  9. ORNL Annual Sustainability Report

    Energy Technology Data Exchange (ETDEWEB)

    Lapsa, Melissa Voss [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nichols, Teresa A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2014-02-01

    As described in this report, we have made substantial progress across the 25 roadmaps of the Sustainable Campus Initiative. The report also outlines our plans to continue integrating sustainable practices into the planning, execution, and evaluation of all ORNL activities. We appreciate your interest in our journey to sustainability, and we welcome your comments, questions, and suggestions.

  10. Toward sustainable logistics

    NARCIS (Netherlands)

    Soysal, Mehmet; Bloemhof-Ruwaard, Jacqueline M.

    2018-01-01

    The fast evolution of sustainability leads to the development of a new fast-growing concept called sustainable logistics management. This research addresses recent business trends and challenges in logistics and their implications for sustainable logistics management. Additionally, we discuss policy

  11. Sustainable Learning Organizations

    Science.gov (United States)

    Velazquez, Luis E.; Esquer, Javier; Munguia, Nora E.; Moure-Eraso, Rafael

    2011-01-01

    Purpose: The purpose of this paper is to debate how companies may better become a sustainable learning organization by offering the most used and insightful concepts of sustainability. Design/methodology/approach: Through literature review, learning organization and sustainability perspectives are explored and compared. Findings: Learning…

  12. Sustainability Annual Report 2013

    OpenAIRE

    2013-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  13. Sustainability Annual Report 2014

    OpenAIRE

    2014-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  14. Sustainability Annual Report 2017

    OpenAIRE

    2017-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  15. Sustainability Annual Report 2011

    OpenAIRE

    2011-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  16. Sustainability Annual Report 2012

    OpenAIRE

    2012-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  17. Sustainability Annual Report 2015

    OpenAIRE

    2015-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  18. Sustainability Annual Report 2016

    OpenAIRE

    2016-01-01

    Every year, Virginia Tech releases a sustainability annual report to show the university’s progress in meeting the sustainability goals. The key sustainability metrics these reports cover include: greenhouse gas (GHG) emissions, energy use intensity, alternative transportation use, recycling, and water consumption.

  19. Managing Proliferation Issues with Iran

    International Nuclear Information System (INIS)

    Nelson, C. Richard; Saltiel, David H.

    2002-01-01

    particular, will continue to play a vital role in determining the extent to which Iran is able to pursue WMD options. Without a fundamental change in the regional security environment, however, there is little reason to expect changes in Iranian WMD and missile policies, and the United States, acting alone and short of war, cannot prevent Iran from ultimately developing WMD and delivery systems. Furthermore, U.S. policies that take a tougher line with Russia, China and North Korea are not likely to lead to more restraint among these potential sources of WMD and missile technology. In the absence of engagement with Iran, unilateral U.S. economic sanctions will remain the principal, if flawed, U.S. policy tool for seeking to prevent Iran from acquiring WMD. The rationale is that by discouraging trade and investment, particularly in Iran's energy sector, the government of Iran will have less revenue to pursue proliferation. Without broad international support for economic isolation, however, such an effort may hinder Iran's WMD programs, though it cannot block them. Finally, options are needed to deal with major failures in nonproliferation efforts. These options include measures to deter Iranian use of WMD, to defend against their use if deterrence fails, and to destroy Iranian WMD capabilities should the need arise

  20. The Microbiome and Sustainable Healthcare

    Science.gov (United States)

    Dietert, Rodney R.; Dietert, Janice M.

    2015-01-01

    Increasing prevalences, morbidity, premature mortality and medical needs associated with non-communicable diseases and conditions (NCDs) have reached epidemic proportions and placed a major drain on healthcare systems and global economies. Added to this are the challenges presented by overuse of antibiotics and increased antibiotic resistance. Solutions are needed that can address the challenges of NCDs and increasing antibiotic resistance, maximize preventative measures, and balance healthcare needs with available services and economic realities. Microbiome management including microbiota seeding, feeding, and rebiosis appears likely to be a core component of a path toward sustainable healthcare. Recent findings indicate that: (1) humans are mostly microbial (in terms of numbers of cells and genes); (2) immune dysfunction and misregulated inflammation are pivotal in the majority of NCDs; (3) microbiome status affects early immune education and risk of NCDs, and (4) microbiome status affects the risk of certain infections. Management of the microbiome to reduce later-life health risk and/or to treat emerging NCDs, to spare antibiotic use and to reduce the risk of recurrent infections may provide a more effective healthcare strategy across the life course particularly when a personalized medicine approach is considered. This review will examine the potential for microbiome management to contribute to sustainable healthcare. PMID:27417751

  1. Advanced high throughput MOX fuel fabrication technology and sustainable development

    International Nuclear Information System (INIS)

    Krellmann, Juergen

    2005-01-01

    The MELOX plant in the south of France together with the La Hague reprocessing plant, are part of the two industrial facilities in charge of closing the nuclear fuel cycle in France. Started up in 1995, MELOX has since accumulated a solid know-how in recycling plutonium recovered from spent uranium fuel into MOX: a fuel blend comprised of both uranium and plutonium oxides. Converting recovered Pu into a proliferation-resistant material that can readily be used to power a civil nuclear reactor, MOX fabrication offers a sustainable solution to safely take advantage of the plutonium's high energy content. Being the first large-capacity industrial facility dedicated to MOX fuel fabrication, MELOX distinguishes itself from the first generation MOX plants with high capacity (around 200 tHM versus around 40 tHM) and several unique operational features designed to improve productivity, reliability and flexibility while maintaining high safety standards. Providing an exemplary reference for high throughput MOX fabrication with 1,000 tHM produced since start-up, the unique process and technologies implemented at MELOX are currently inspiring other MOX plant construction projects (in Japan with the J-MOX plant, in the US and in Russia as part of the weapon-grade plutonium inventory reduction). Spurred by the growing international demand, MELOX has embarked upon an ambitious production development and diversification plan. Starting from an annual level of 100 tons of heavy metal (tHM), MELOX demonstrated production capacity is continuously increasing: MELOX is now aiming for a minimum of 140 tHM by the end of 2005, with the ultimate ambition of reaching the full capacity of the plant (around 200 tHM) in the near future. With regards to its activity, MELOX also remains deeply committed to sustainable development in a consolidated involvement within AREVA group. The French minister of Industry, on August 26th 2005, acknowledged the benefits of MOX fuel production at MELOX: 'In

  2. Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation.

    OpenAIRE

    Kubben, F J; Peeters-Haesevoets, A; Engels, L G; Baeten, C G; Schutte, B; Arends, J W; Stockbrügger, R W; Blijham, G H

    1994-01-01

    Immunohistochemistry of the S phase related proliferating cell nuclear antigen (PCNA) was studied as an alternative to ex-vivo bromodeoxyuridine (BrdU) immunohistochemistry for assessment of human colonic cell proliferation. From 16 subjects without colonic disease biopsy specimens were collected from five different sites along the colorectum and processed for BrdU and PCNA immunohistochemistry. The mean proliferation index of PCNA was significantly higher at 133% of the value obtained with B...

  3. Antimicrobial Resistance

    Science.gov (United States)

    ... least 10 countries (Australia, Austria, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom ... plan Global report on surveillance Country situation analysis Policy to combat antimicrobial resistance More on antimicrobial resistance ...

  4. Antimicrobial Resistance

    Science.gov (United States)

    ... can prevent and manage antimicrobial resistance. It is collaborating with partners to strengthen the evidence base and ... on the global action plan. WHO has been leading multiple initiatives to address antimicrobial resistance: World Antibiotic ...

  5. Life Cycle Sustainability Dashboard

    DEFF Research Database (Denmark)

    Traverso, Marzia; Finkbeiner, Matthias; Jørgensen, Andreas

    2012-01-01

    One method to assess the sustainability performance of products is life cycle sustainability assessment (LCSA), which assesses product performance considering the environmental,economic, and social dimensions of the life cycle. The results of LCSA can be used to compare different products...... of sustainability is the communicability of the results by means of a graphical representation (a cartogram), characterized by a suitable chromatic scale and ranking score. The integration of LCSA and the dashboard of sustainability into a so-called Life Cycle Sustainability Dashboard (LCSD) is described here...

  6. LCA and Sustainability

    DEFF Research Database (Denmark)

    Moltesen, Andreas; Bjørn, Anders

    2018-01-01

    LCA is often presented as a sustainability assessment tool. This chapter analyses the relationship between LCA and sustainability. This is done by first outlining the history of the sustainability concept, which gained momentum with the Brundtland Commission’s report ‘Our Common Future report...... is then demonstrated, and the strategy of LCA to achieving environmental protection, namely to guide the reduction of environmental impacts per delivery of a function, is explained. The attempt to broaden the scope of LCA, beyond environmental protection, by so-called life cycle sustainability assessment (LCSA......) is outlined. Finally, the limitations of LCA in guiding a sustainable development are discussed....

  7. Nuclear arbitration: Interpreting non-proliferation agreements

    International Nuclear Information System (INIS)

    Tzeng, Peter

    2015-01-01

    At the core of the nuclear non-proliferation regime lie international agreements. These agreements include, inter alia, the Nuclear Non-proliferation Treaty, nuclear co-operation agreements and nuclear export control agreements.1 States, however, do not always comply with their obligations under these agreements. In response, commentators have proposed various enforcement mechanisms to promote compliance. The inconvenient truth, however, is that states are generally unwilling to consent to enforcement mechanisms concerning issues as critical to national security as nuclear non-proliferation.3 This article suggests an alternative solution to the non-compliance problem: interpretation mechanisms. Although an interpretation mechanism does not have the teeth of an enforcement mechanism, it can induce compliance by providing an authoritative interpretation of a legal obligation. Interpretation mechanisms would help solve the non-compliance problem because, as this article shows, in many cases of alleged non-compliance with a non-proliferation agreement, the fundamental problem has been the lack of an authoritative interpretation of the agreement, not the lack of an enforcement mechanism. Specifically, this article proposes arbitration as the proper interpretation mechanism for non-proliferation agreements. It advocates the establishment of a 'Nuclear Arbitration Centre' as an independent branch of the International Atomic Energy Agency (IAEA), and recommends the gradual introduction of arbitration clauses into the texts of non-proliferation agreements. Section I begins with a discussion of international agreements in general and the importance of interpretation and enforcement mechanisms. Section II then discusses nuclear non-proliferation agreements and their lack of interpretation and enforcement mechanisms. Section III examines seven case studies of alleged non-compliance with non-proliferation agreements in order to show that the main problem in many cases

  8. Identification of chimeric antigen receptors that mediate constitutive or inducible proliferation of T cells.

    Science.gov (United States)

    Frigault, Matthew J; Lee, Jihyun; Basil, Maria Ciocca; Carpenito, Carmine; Motohashi, Shinichiro; Scholler, John; Kawalekar, Omkar U; Guedan, Sonia; McGettigan, Shannon E; Posey, Avery D; Ang, Sonny; Cooper, Laurence J N; Platt, Jesse M; Johnson, F Brad; Paulos, Chrystal M; Zhao, Yangbing; Kalos, Michael; Milone, Michael C; June, Carl H

    2015-04-01

    This study compared second-generation chimeric antigen receptors (CAR) encoding signaling domains composed of CD28, ICOS, and 4-1BB (TNFRSF9). Here, we report that certain CARs endow T cells with the ability to undergo long-term autonomous proliferation. Transduction of primary human T cells with lentiviral vectors encoding some of the CARs resulted in sustained proliferation for up to 3 months following a single stimulation through the T-cell receptor (TCR). Sustained numeric expansion was independent of cognate antigen and did not require the addition of exogenous cytokines or feeder cells after a single stimulation of the TCR and CD28. Results from gene array and functional assays linked sustained cytokine secretion and expression of T-bet (TBX21), EOMES, and GATA-3 to the effect. Sustained expression of the endogenous IL2 locus has not been reported in primary T cells. Sustained proliferation was dependent on CAR structure and high expression, the latter of which was necessary but not sufficient. The mechanism involves constitutive signaling through NF-κB, AKT, ERK, and NFAT. The propagated CAR T cells retained a diverse TCR repertoire, and cellular transformation was not observed. The CARs with a constitutive growth phenotype displayed inferior antitumor effects and engraftment in vivo. Therefore, the design of CARs that have a nonconstitutive growth phenotype may be a strategy to improve efficacy and engraftment of CAR T cells. The identification of CARs that confer constitutive or nonconstitutive growth patterns may explain observations that CAR T cells have differential survival patterns in clinical trials. ©2015 American Association for Cancer Research.

  9. 3-Methylcholanthrene inhibits lymphocyte proliferation and increases intracellular calcium levels in common carp (Cyprinus carpio L)

    International Nuclear Information System (INIS)

    Reynaud, S.; Duchiron, C.; Deschaux, P.

    2003-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are an important class of environmental pollutants that are known to be carcinogenic and immunotoxic. Many authors have focused on macrophage activities in fish exposed to PAHs. However, fewer studies have reported decrease in specific immunity in such fish. We investigated the intracellular mechanisms by which the 3-methylcholanthrene (3-MC) decreased lymphocyte proliferation in carp. T- and B-lymphocyte proliferation induced by Concanavalin A (Con A) and lipopolysaccharide (LPS) were inhibited by 3-MC (0.5-50 μM). 3-MC also produced a rapid and a sustained increase in intracellular calcium concentration ([Ca 2+ ] i ) (2 h minimum). However, the cytochrome P450 1A and Ah receptor inhibitor, α-naphtoflavone (a-NF), also inhibited lymphocyte proliferation and did not reverse the effects of 3-MC. Moreover, since a-NF and 3-MC increased [Ca 2+ ] i and inhibited lymphocyte proliferation it was possible that calcium release played a role in 3-MC-inhibited lymphocyte proliferation. The rise in [Ca 2+ ] i induced by 3-MC was potentiated by the inhibitor of the endoplasmic reticulum calcium ATPases, thapsigargin. Treating cells with 3-MC decreased calcium mobilization caused by thapsigargin. These results suggest that 3-MC acts on the endoplasmic reticulum, perhaps directly on calcium ATPases, to increase intracellular calcium levels in carp leucocytes

  10. Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study*

    Science.gov (United States)

    Zhan, He-qing; Xia, Ling; Shou, Guo-fa; Zang, Yun-liang; Liu, Feng; Crozier, Stuart

    2014-01-01

    In this study, the effects of cardiac fibroblast proliferation on cardiac electric excitation conduction and mechanical contraction were investigated using a proposed integrated myocardial-fibroblastic electromechanical model. At the cellular level, models of the human ventricular myocyte and fibroblast were modified to incorporate a model of cardiac mechanical contraction and cooperativity mechanisms. Cellular electromechanical coupling was realized with a calcium buffer. At the tissue level, electrical excitation conduction was coupled to an elastic mechanics model in which the finite difference method (FDM) was used to solve electrical excitation equations, and the finite element method (FEM) was used to solve mechanics equations. The electromechanical properties of the proposed integrated model were investigated in one or two dimensions under normal and ischemic pathological conditions. Fibroblast proliferation slowed wave propagation, induced a conduction block, decreased strains in the fibroblast proliferous tissue, and increased dispersions in depolarization, repolarization, and action potential duration (APD). It also distorted the wave-front, leading to the initiation and maintenance of re-entry, and resulted in a sustained contraction in the proliferous areas. This study demonstrated the important role that fibroblast proliferation plays in modulating cardiac electromechanical behaviour and which should be considered in planning future heart-modeling studies. PMID:24599687

  11. Fur and Sustainability

    DEFF Research Database (Denmark)

    Skjold, Else; Csaba, Fabian

    2016-01-01

    This paper explores the notion of deeper luxury, which insists that 'real' luxury should involve sustainable practices in the production and consumption of luxury goods. It traces historical and recent developments in the field of fur, to understand the implications, uncertainties and ambiguities...... of luxury’s confrontation with sustainability. Considering fur in relation to future standards for luxury products, we raise questions about moral problematisation and justification of luxury in terms of sustainability. We first examine the encounter of luxury with sustainability and explain...... the significance of the notion of ‘deeper luxury’. After taking stock of the impact of sustainability on luxury and various directions in which sustainable luxury is evolving, we discuss concepts of sustainable development in relation to the history of moral problematisation of luxury. This leads to the case...

  12. Sustainability index for Taipei

    International Nuclear Information System (INIS)

    Lee, Y.-J.; Huang Chingming

    2007-01-01

    Sustainability indicators are an effective means of determining whether a city is moving towards sustainable development (SD). After considering the characteristics of Taipei, Taiwan, discussions with experts, scholars and government departments and an exhaustive literature review, this study selected 51 sustainability indicators corresponding to the socio-economic characteristic of Taipei City. Such indicators should be regarded as a basis for assessing SD in Taipei City. The 51 indicators are classified into economic, social, environmental and institutional dimensions. Furthermore, statistical data is adopted to identify the trend of SD from 1994 to 2004. Moreover, the sustainability index is calculated for the four dimensions and for Taipei as a whole. Analysis results demonstrate that social and environmental indicators are moving towards SD, while economic and institutional dimensions are performing relatively poorly. However, since 2002, the economic sustainability index has gradually moved towards SD. Overall, the Taipei sustainability index indicates a gradual trend towards sustainable development during the past 11 years

  13. Sustainability and Entrepreneurial Action

    DEFF Research Database (Denmark)

    Korsgaard, Steffen T.; Anderson, Alistair

    Abstract Objectives - This paper explores how entrepreneurial action can lead to environmental sustainability. It builds on the assumption that the creation of sustainble practices is one of the most important challenges facing the global society, and that entrepreneurial action is a vital......: resource oriented sustainable entrepreneurial action.  Approach - The paper uses a case study approach to build deeper theoretical knowledge of environmentally sustainable entrepreneurship.  Results - The paper identifies and analyses a distinct form of sustainable entrepreneurship -  resource oriented...... entrepreneurship - which uses bricolage in various ways to create sustainable solutions. Implications and value - The concept of resource oriented sustainable entrepreneurship contributes to the theoretical understanding of how entrepreneurial action can support sustainability, Furthermore the case study has...

  14. Suburbanization and sustainability in metropolitan Moscow.

    Science.gov (United States)

    Mason, Robert J; Nigmatullina, Liliya

    2011-01-01

    Although Soviet-era urban-growth controls produced relatively sustainable metropolitan development patterns, low-density suburban sprawl has accelerated markedly in modern Russia. Distinctive features of Moscow's development history are its greenbelt, which dates from 1935 and is becoming increasingly fragmented, proliferation of satellite cities at the urban fringe, conversion of seasonal dachas into full-time residences, the very exclusive Rublevo Uspenskoe Highway development, and today's crippling traffic congestion. The recent economic crisis has slowed development and actually increased the supply of “economy-class” single-family homes, for which there is much pent-up desire but insufficient credit availability to meet the demand. A renewed commitment to sustainability's triple bottom line—environmental quality, equity, and economic prosperity—will require greater government transparency and fairness, stronger planning controls, and an expanded public transportation system.

  15. Sustaining Collective Action in Urbanizing China

    DEFF Research Database (Denmark)

    Kuang, Xianwen; Goebel, Christian

    2013-01-01

    The recent years have seen a proliferation of scholarship on protests and other forms of collective action in China. Important insights have been gained into how conflicts between social groups and local governments begin, which strategies and instruments protesters apply, and under which...... challenges of sustaining collective action in China: the continuing existence of substantial grievances, the re-activation of strong social ties, the presence of unifying frames and an adaptive protest leadership. The comparison shows that especially the last factor is crucial: while the two villages were...... similar in all other respects, leadership in Village B was far more adaptive in Village A, which goes a long way towards explaining why collective action could be sustained twice as long in Village B....

  16. Health and sustainability.

    Science.gov (United States)

    Kjӕrgård, Bente; Land, Birgit; Bransholm Pedersen, Kirsten

    2014-09-01

    In the present article, we explore how sustainable development strategies and health promotion strategies can be bridged. The concept of the 'duality of structure' is taken as our starting point for understanding the linkages between health promotion and sustainable development, and for uncovering the structural properties or conditions which either enable or constrain sustainable public health initiatives. We argue that strategies towards health promotion are not sufficiently integrated with strategies for sustainable development, and thus political strategies aimed at solving health problems or sustainability problems may cause new, undesired and unforeseen environmental or health problems. First, we explore how the relation between health and sustainability is articulated in international policy documents. Next, we develop a model for understanding the relation between health promotion and sustainability. Third, we use examples from agriculture and food production to illustrate that health and sustainability are mutually enabling and constraining. We conclude that while the renewed focus on food security and food inequalities has brought the health and sustainability dimensions of the food system onto the political agenda, the conceptualization of duality between health and sustainability could be a new platform for a critical and theoretical stance towards the market-oriented food system strategy. Thinking along the lines of duality means that the integration of health promotion strategies and sustainable development strategies cannot be based on an approach to integration in which either health or sustainability is given precedence over the other. From a duality perspective, integration means conceiving sustainability from a health perspective and health from a sustainability perspective. © The Author (2013). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol.

    Science.gov (United States)

    Cruz, Pamela; Torres, Cristian; Ramírez, María Eugenia; Epuñán, María José; Valladares, Luis Emilio; Sierralta, Walter Daniel

    2010-05-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E(2)) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E(2), and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E(2) in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E(2)-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels.

  18. Hydroxyurea treatment inhibits proliferation of Cryptococcus neoformans in mice

    Directory of Open Access Journals (Sweden)

    Kaushlendra eTripathi

    2012-05-01

    Full Text Available The fungal pathogen Cryptococcus neoformans (Cn is a serious threat to immunocompromised individuals, especially for HIV patients who develop meningoencephalitis. For effective cryptococcal treatment, novel antifungal drugs or innovative combination therapies are needed. Recently, sphingolipids have emerged as important bioactive molecules in the regulation of microbial pathogenesis. Previously we reported that the sphingolipid pathway gene, ISC1, which is responsible for ceramide production, is a major virulence factor in Cn infection. Here we report our studies of the role of ISC1 during genotoxic stress induced by the antineoplastic hydroxyurea (HU and methylmethane sulfonate (MMS, which affect DNA replication and genome integrity. We observed that Cn cells lacking ISC1 are highly sensitive to HU and MMS in a rich culture medium. HU affected cell division of Cn cells lacking the ISC1 gene, resulting in cell clusters. Cn ISC1, when expressed in a Saccharomyces cerevisiae (Sc strain lacking its own ISC1 gene, restored HU resistance. In macrophage-like cells, although HU affected the proliferation of WT Cn cells by 50% at the concentration tested, HU completely inhibited Cn isc1-delta cell proliferation. Interestingly, our preliminary data show that mice infected with WT or Cn isc1-delta cells and subsequently treated with HU had longer lifespans than untreated, infected control mice. Our work suggests that the sphingolipid pathway gene, ISC1, is a likely target for combination therapy with traditional drugs such as HU.

  19. Antibiotic resistance

    Directory of Open Access Journals (Sweden)

    Marianne Frieri

    2017-07-01

    Full Text Available Summary: Antimicrobial resistance in bacterial pathogens is a challenge that is associated with high morbidity and mortality. Multidrug resistance patterns in Gram-positive and -negative bacteria are difficult to treat and may even be untreatable with conventional antibiotics. There is currently a shortage of effective therapies, lack of successful prevention measures, and only a few new antibiotics, which require development of novel treatment options and alternative antimicrobial therapies. Biofilms are involved in multidrug resistance and can present challenges for infection control. Virulence, Staphylococcus aureus, Clostridium difficile infection, vancomycin-resistant enterococci, and control in the Emergency Department are also discussed. Keywords: Antibiotic resistance, Biofilms, Infections, Public health, Emergency Department

  20. The possibility of life proliferation from Enceladus

    Science.gov (United States)

    Czechowski, Leszek

    2016-04-01

    Introduction: Enceladus is a medium-sized icy satellite (MIS) of Saturn. MIS are built of mixtures of rocks and ices. Enceladus with its radius of 250 km is one of the smallest of MIS, however, it is geologically active. According to [1]: "For life to have emerged […] on the early Earth, a sustained source of chemically transducible energy was essential. The serpentinization process is emerging as an increasingly likely source of that energy. Serpentinization of ultramafic crust would have continuously supplied hydrogen, methane, […] to off-ridge alkaline hydrothermal springs that interfaced with the metal-rich carbonic Hadean Ocean" (see also [2]). We consider here conditions for origin of life in early Enceladus and possible proliferation of the life from this satellite to the rest of Solar System. Mass of serpentinite: The serpentinization on the Earth is found in neovolcanic zones along mid-oceanic spreading centers. However, only in small part of them the hydrothermal activity really occurs. After [3] we consider the following reaction: Mg2SiO4 + MgSiO3 + 2H2O -> Mg3Si2O5(OH)4 . This reaction releases 241 000 J per kg of serpentine produced. Simple calculations (e.g. [4]) indicate that mass fraction of silicatesfmas in Enceladus is ˜0.646, hence the total mass of its silicate is ˜6.97 1019 kg. [4] found that the early core in Enceladus was a relatively cold structure built from loosely packed grains with water between them. At that time, there was not mechanism of removing the water. Since rocks are permeable up to the pressure of ˜300 MPa then the entire core of Enceladus was probably permeable for liquids. This could lead to formation of extensive hydrothermal convective systems. T-p conditions in Enceladus: The pressure in the center of Enceladus is ˜2.3 107 Pa that corresponds to pressure on the depth 2300 m in a terrestrial ocean. The evolution of temperature in the Enceladus interior for the first a few hundreds Myr is considered by [4]. If